Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the ANTIGEN (or a very similar shape) that induced their synthesis in cells of the lymphoid series (especially PLASMA CELLS).
The property of antibodies which enables them to react with some ANTIGENIC DETERMINANTS and not with others. Specificity is dependent on chemical composition, physical forces, and molecular structure at the binding site.
Immunoglobulins produced in response to VIRAL ANTIGENS.
Immunoglobulins produced in a response to BACTERIAL ANTIGENS.
Antibodies produced by a single clone of cells.
The production of ANTIBODIES by proliferating and differentiated B-LYMPHOCYTES under stimulation by ANTIGENS.
Antibodies that reduce or abolish some biological activity of a soluble antigen or infectious agent, usually a virus.
A measure of the binding strength between antibody and a simple hapten or antigen determinant. It depends on the closeness of stereochemical fit between antibody combining sites and antigen determinants, on the size of the area of contact between them, and on the distribution of charged and hydrophobic groups. It includes the concept of "avidity," which refers to the strength of the antigen-antibody bond after formation of reversible complexes.
Test for tissue antigen using either a direct method, by conjugation of antibody with fluorescent dye (FLUORESCENT ANTIBODY TECHNIQUE, DIRECT) or an indirect method, by formation of antigen-antibody complex which is then labeled with fluorescein-conjugated anti-immunoglobulin antibody (FLUORESCENT ANTIBODY TECHNIQUE, INDIRECT). The tissue is then examined by fluorescence microscopy.
Antibodies which react with the individual structural determinants (idiotopes) on the variable region of other antibodies.
Local surface sites on antibodies which react with antigen determinant sites on antigens (EPITOPES.) They are formed from parts of the variable regions of FAB FRAGMENTS.
Antibodies reactive with HIV ANTIGENS.
Sites on an antigen that interact with specific antibodies.
Immunoglobulins induced by antigens specific for tumors other than the normally occurring HISTOCOMPATIBILITY ANTIGENS.
Immunoglobulins produced in a response to PROTOZOAN ANTIGENS.
Autoantibodies directed against various nuclear antigens including DNA, RNA, histones, acidic nuclear proteins, or complexes of these molecular elements. Antinuclear antibodies are found in systemic autoimmune diseases including systemic lupus erythematosus, Sjogren's syndrome, scleroderma, polymyositis, and mixed connective tissue disease.
Serological reactions in which an antiserum against one antigen reacts with a non-identical but closely related antigen.
A class of immunoglobulin bearing mu chains (IMMUNOGLOBULIN MU-CHAINS). IgM can fix COMPLEMENT. The name comes from its high molecular weight and originally being called a macroglobulin.
Antibodies that react with self-antigens (AUTOANTIGENS) of the organism that produced them.
Immunoglobulins produced in a response to FUNGAL ANTIGENS.
The measurement of infection-blocking titer of ANTISERA by testing a series of dilutions for a given virus-antiserum interaction end-point, which is generally the dilution at which tissue cultures inoculated with the serum-virus mixtures demonstrate cytopathology (CPE) or the dilution at which 50% of test animals injected with serum-virus mixtures show infectivity (ID50) or die (LD50).
The processes triggered by interactions of ANTIBODIES with their ANTIGENS.
Antibodies, often monoclonal, in which the two antigen-binding sites are specific for separate ANTIGENIC DETERMINANTS. They are artificial antibodies produced by chemical crosslinking, fusion of HYBRIDOMA cells, or by molecular genetic techniques. They function as the main mediators of targeted cellular cytotoxicity and have been shown to be efficient in the targeting of drugs, toxins, radiolabeled haptens, and effector cells to diseased tissue, primarily tumors.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
A form of antibodies consisting only of the variable regions of the heavy and light chains (FV FRAGMENTS), connected by a small linker peptide. They are less immunogenic than complete immunoglobulin and thus have potential therapeutic use.
Antibodies that inhibit the reaction between ANTIGEN and other antibodies or sensitized T-LYMPHOCYTES (e.g., antibodies of the IMMUNOGLOBULIN G class that compete with IGE antibodies for antigen, thereby blocking an allergic response). Blocking antibodies that bind tumors and prevent destruction of tumor cells by CYTOTOXIC T-LYMPHOCYTES have also been called enhancing antibodies. (Rosen et al., Dictionary of Immunology, 1989)
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of IgG, for example, IgG1, IgG2A, and IgG2B.
The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes IMMUNE COMPLEX DISEASES.
Univalent antigen-binding fragments composed of one entire IMMUNOGLOBULIN LIGHT CHAIN and the amino terminal end of one of the IMMUNOGLOBULIN HEAVY CHAINS from the hinge region, linked to each other by disulfide bonds. Fab contains the IMMUNOGLOBULIN VARIABLE REGIONS, which are part of the antigen-binding site, and the first IMMUNOGLOBULIN CONSTANT REGIONS. This fragment can be obtained by digestion of immunoglobulins with the proteolytic enzyme PAPAIN.
Antibodies elicited in a different species from which the antigen originated. These antibodies are directed against a wide variety of interspecies-specific antigens, the best known of which are Forssman, Hanganutziu-Deicher (H-D), and Paul-Bunnell (P-B). Incidence of antibodies to these antigens--i.e., the phenomenon of heterophile antibody response--is useful in the serodiagnosis, pathogenesis, and prognosis of infection and latent infectious states as well as in cancer classification.
Antibodies that can catalyze a wide variety of chemical reactions. They are characterized by high substrate specificity and share many mechanistic features with enzymes.
The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.
Represents 15-20% of the human serum immunoglobulins, mostly as the 4-chain polymer in humans or dimer in other mammals. Secretory IgA (IMMUNOGLOBULIN A, SECRETORY) is the main immunoglobulin in secretions.
Antibodies from non-human species whose protein sequences have been modified to make them nearly identical with human antibodies. If the constant region and part of the variable region are replaced, they are called humanized. If only the constant region is modified they are called chimeric. INN names for humanized antibodies end in -zumab.
A form of fluorescent antibody technique commonly used to detect serum antibodies and immune complexes in tissues and microorganisms in specimens from patients with infectious diseases. The technique involves formation of an antigen-antibody complex which is labeled with fluorescein-conjugated anti-immunoglobulin antibody. (From Bennington, Saunders Dictionary & Encyclopedia of Laboratory Medicine and Technology, 1984)
Cells artificially created by fusion of activated lymphocytes with neoplastic cells. The resulting hybrid cells are cloned and produce pure MONOCLONAL ANTIBODIES or T-cell products, identical to those produced by the immunologically competent parent cell.
Serum that contains antibodies. It is obtained from an animal that has been immunized either by ANTIGEN injection or infection with microorganisms containing the antigen.
Methods used for studying the interactions of antibodies with specific regions of protein antigens. Important applications of epitope mapping are found within the area of immunochemistry.
Autoantibodies directed against phospholipids. These antibodies are characteristically found in patients with systemic lupus erythematosus (LUPUS ERYTHEMATOSUS, SYSTEMIC;), ANTIPHOSPHOLIPID SYNDROME; related autoimmune diseases, some non-autoimmune diseases, and also in healthy individuals.
Deliberate stimulation of the host's immune response. ACTIVE IMMUNIZATION involves administration of ANTIGENS or IMMUNOLOGIC ADJUVANTS. PASSIVE IMMUNIZATION involves administration of IMMUNE SERA or LYMPHOCYTES or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow).
Substances that are recognized by the immune system and induce an immune reaction.
Immunologic techniques based on the use of: (1) enzyme-antibody conjugates; (2) enzyme-antigen conjugates; (3) antienzyme antibody followed by its homologous enzyme; or (4) enzyme-antienzyme complexes. These are used histologically for visualizing or labeling tissue specimens.
Established cell cultures that have the potential to propagate indefinitely.
Substances elaborated by bacteria that have antigenic activity.
An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed.
Antigens on surfaces of cells, including infectious or foreign cells or viruses. They are usually protein-containing groups on cell membranes or walls and may be isolated.
Transfer of immunity from immunized to non-immune host by administration of serum antibodies, or transplantation of lymphocytes (ADOPTIVE TRANSFER).
Proteins prepared by recombinant DNA technology.
Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.
A technique using antibodies for identifying or quantifying a substance. Usually the substance being studied serves as antigen both in antibody production and in measurement of antibody by the test substance.
Partial immunoglobulin molecules resulting from selective cleavage by proteolytic enzymes or generated through PROTEIN ENGINEERING techniques.
The sum of the weight of all the atoms in a molecule.
Histochemical localization of immunoreactive substances using labeled antibodies as reagents.
Substances elaborated by viruses that have antigenic activity.
Immunologic method used for detecting or quantifying immunoreactive substances. The substance is identified by first immobilizing it by blotting onto a membrane and then tagging it with labeled antibodies.
Classic quantitative assay for detection of antigen-antibody reactions using a radioactively labeled substance (radioligand) either directly or indirectly to measure the binding of the unlabeled substance to a specific antibody or other receptor system. Non-immunogenic substances (e.g., haptens) can be measured if coupled to larger carrier proteins (e.g., bovine gamma-globulin or human serum albumin) capable of inducing antibody formation.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.
Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation.
Serologic tests based on inactivation of complement by the antigen-antibody complex (stage 1). Binding of free complement can be visualized by addition of a second antigen-antibody system such as red cells and appropriate red cell antibody (hemolysin) requiring complement for its completion (stage 2). Failure of the red cells to lyse indicates that a specific antigen-antibody reaction has taken place in stage 1. If red cells lyse, free complement is present indicating no antigen-antibody reaction occurred in stage 1.
Sensitive tests to measure certain antigens, antibodies, or viruses, using their ability to agglutinate certain erythrocytes. (From Stedman, 26th ed)
Serologic tests in which a known quantity of antigen is added to the serum prior to the addition of a red cell suspension. Reaction result is expressed as the smallest amount of antigen which causes complete inhibition of hemagglutination.
Autoantibodies directed against cytoplasmic constituents of POLYMORPHONUCLEAR LEUKOCYTES and/or MONOCYTES. They are used as specific markers for GRANULOMATOSIS WITH POLYANGIITIS and other diseases, though their pathophysiological role is not clear. ANCA are routinely detected by indirect immunofluorescence with three different patterns: c-ANCA (cytoplasmic), p-ANCA (perinuclear), and atypical ANCA.
That region of the immunoglobulin molecule that varies in its amino acid sequence and composition, and comprises the binding site for a specific antigen. It is located at the N-terminus of the Fab fragment of the immunoglobulin. It includes hypervariable regions (COMPLEMENTARITY DETERMINING REGIONS) and framework regions.
EPIDEMIOLOGIC STUDIES based on the detection through serological testing of characteristic change in the serum level of specific ANTIBODIES. Latent subclinical infections and carrier states can thus be detected in addition to clinically overt cases.
Unique genetically-controlled determinants present on ANTIBODIES whose specificity is limited to a single group of proteins (e.g., another antibody molecule or an individual myeloma protein). The idiotype appears to represent the antigenicity of the antigen-binding site of the antibody and to be genetically codetermined with it. The idiotypic determinants have been precisely located to the IMMUNOGLOBULIN VARIABLE REGION of both immunoglobin polypeptide chains.
Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.
Techniques used to demonstrate or measure an immune response, and to identify or measure antigens using antibodies.
Proteins, glycoprotein, or lipoprotein moieties on surfaces of tumor cells that are usually identified by monoclonal antibodies. Many of these are of either embryonic or viral origin.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
Techniques for removal by adsorption and subsequent elution of a specific antibody or antigen using an immunosorbent containing the homologous antigen or antibody.
Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response.
The phenomenon of immense variability characteristic of ANTIBODIES. It enables the IMMUNE SYSTEM to react specifically against the essentially unlimited kinds of ANTIGENS it encounters. Antibody diversity is accounted for by three main theories: (1) the Germ Line Theory, which holds that each antibody-producing cell has genes coding for all possible antibody specificities, but expresses only the one stimulated by antigen; (2) the Somatic Mutation Theory, which holds that antibody-producing cells contain only a few genes, which produce antibody diversity by mutation; and (3) the Gene Rearrangement Theory, which holds that antibody diversity is generated by the rearrangement of IMMUNOGLOBULIN VARIABLE REGION gene segments during the differentiation of the ANTIBODY-PRODUCING CELLS.
Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.
A collection of cloned peptides, or chemically synthesized peptides, frequently consisting of all possible combinations of amino acids making up an n-amino acid peptide.
Antibodies to the HEPATITIS C ANTIGENS including antibodies to envelope, core, and non-structural proteins.
Antibodies from an individual that react with ISOANTIGENS of another individual of the same species.
The classes of immunoglobulins found in any species of animal. In man there are nine classes that migrate in five different groups in electrophoresis; they each consist of two light and two heavy protein chains, and each group has distinguishing structural and functional properties.
Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.
Multi-subunit proteins which function in IMMUNITY. They are produced by B LYMPHOCYTES from the IMMUNOGLOBULIN GENES. They are comprised of two heavy (IMMUNOGLOBULIN HEAVY CHAINS) and two light chains (IMMUNOGLOBULIN LIGHT CHAINS) with additional ancillary polypeptide chains depending on their isoforms. The variety of isoforms include monomeric or polymeric forms, and transmembrane forms (B-CELL ANTIGEN RECEPTORS) or secreted forms (ANTIBODIES). They are divided by the amino acid sequence of their heavy chains into five classes (IMMUNOGLOBULIN A; IMMUNOGLOBULIN D; IMMUNOGLOBULIN E; IMMUNOGLOBULIN G; IMMUNOGLOBULIN M) and various subclasses.
Antibodies obtained from a single clone of cells grown in mice or rats.
Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins.
Administration of vaccines to stimulate the host's immune response. This includes any preparation intended for active immunological prophylaxis.
Elements of limited time intervals, contributing to particular results or situations.
Antibodies to the HEPATITIS B ANTIGENS, including antibodies to the surface (Australia) and core of the Dane particle and those to the "e" antigens.
Technique involving the diffusion of antigen or antibody through a semisolid medium, usually agar or agarose gel, with the result being a precipitin reaction.
Binary classification measures to assess test results. Sensitivity or recall rate is the proportion of true positives. Specificity is the probability of correctly determining the absence of a condition. (From Last, Dictionary of Epidemiology, 2d ed)
The interaction of two or more substrates or ligands with the same binding site. The displacement of one by the other is used in quantitative and selective affinity measurements.
Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.
Resistance to a disease-causing agent induced by the introduction of maternal immunity into the fetus by transplacental transfer or into the neonate through colostrum and milk.
Antibodies specific to INSULIN.
Serum glycoproteins participating in the host defense mechanism of COMPLEMENT ACTIVATION that creates the COMPLEMENT MEMBRANE ATTACK COMPLEX. Included are glycoproteins in the various pathways of complement activation (CLASSICAL COMPLEMENT PATHWAY; ALTERNATIVE COMPLEMENT PATHWAY; and LECTIN COMPLEMENT PATHWAY).
A chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys, and serosal membranes. It is of unknown etiology, but is thought to represent a failure of the regulatory mechanisms of the autoimmune system. The disease is marked by a wide range of system dysfunctions, an elevated erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow.
An encapsulated lymphatic organ through which venous blood filters.
Endogenous tissue constituents that have the ability to interact with AUTOANTIBODIES and cause an immune response.
Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.
Serologic tests in which a positive reaction manifested by visible CHEMICAL PRECIPITATION occurs when a soluble ANTIGEN reacts with its precipitins, i.e., ANTIBODIES that can form a precipitate.
The restriction of a characteristic behavior, anatomical structure or physical system, such as immune response; metabolic response, or gene or gene variant to the members of one species. It refers to that property which differentiates one species from another but it is also used for phylogenetic levels higher or lower than the species.
Any part or derivative of any protozoan that elicits immunity; malaria (Plasmodium) and trypanosome antigens are presently the most frequently encountered.
Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.
Diagnostic procedures involving immunoglobulin reactions.
The phenomenon of antibody-mediated target cell destruction by non-sensitized effector cells. The identity of the target cell varies, but it must possess surface IMMUNOGLOBULIN G whose Fc portion is intact. The effector cell is a "killer" cell possessing Fc receptors. It may be a lymphocyte lacking conventional B- or T-cell markers, or a monocyte, macrophage, or polynuclear leukocyte, depending on the identity of the target cell. The reaction is complement-independent.
An immunoglobulin fragment composed of one variable domain from an IMMUNOGLOBULIN HEAVY CHAIN or IMMUNOGLOBULIN LIGHT CHAIN.
Polysaccharides found in bacteria and in capsules thereof.
The rate dynamics in chemical or physical systems.
A chromatographic technique that utilizes the ability of biological molecules to bind to certain ligands specifically and reversibly. It is used in protein biochemistry. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)
Unstable isotopes of iodine that decay or disintegrate emitting radiation. I atoms with atomic weights 117-139, except I 127, are radioactive iodine isotopes.
Suspensions of attenuated or killed bacteria administered for the prevention or treatment of infectious bacterial disease.
The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.
Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations, or by parent x offspring matings carried out with certain restrictions. All animals within an inbred strain trace back to a common ancestor in the twentieth generation.
The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.
Field of chemistry that pertains to immunological phenomena and the study of chemical reactions related to antigen stimulation of tissues. It includes physicochemical interactions between antigens and antibodies.
Layers of protein which surround the capsid in animal viruses with tubular nucleocapsids. The envelope consists of an inner layer of lipids and virus specified proteins also called membrane or matrix proteins. The outer layer consists of one or more types of morphological subunits called peplomers which project from the viral envelope; this layer always consists of glycoproteins.
The largest of polypeptide chains comprising immunoglobulins. They contain 450 to 600 amino acid residues per chain, and have molecular weights of 51-72 kDa.
Accumulation of a drug or chemical substance in various organs (including those not relevant to its pharmacologic or therapeutic action). This distribution depends on the blood flow or perfusion rate of the organ, the ability of the drug to penetrate organ membranes, tissue specificity, protein binding. The distribution is usually expressed as tissue to plasma ratios.
A specific immune response elicited by a specific dose of an immunologically active substance or cell in an organism, tissue, or cell.
Disorders that are characterized by the production of antibodies that react with host tissues or immune effector cells that are autoreactive to endogenous peptides.
Differentiation antigens residing on mammalian leukocytes. CD stands for cluster of differentiation, which refers to groups of monoclonal antibodies that show similar reactivity with certain subpopulations of antigens of a particular lineage or differentiation stage. The subpopulations of antigens are also known by the same CD designation.
Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.
Glycoproteins found on the membrane or surface of cells.
Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.
Radiotherapy where cytotoxic radionuclides are linked to antibodies in order to deliver toxins directly to tumor targets. Therapy with targeted radiation rather than antibody-targeted toxins (IMMUNOTOXINS) has the advantage that adjacent tumor cells, which lack the appropriate antigenic determinants, can be destroyed by radiation cross-fire. Radioimmunotherapy is sometimes called targeted radiotherapy, but this latter term can also refer to radionuclides linked to non-immune molecules (see RADIOTHERAPY).
Morphologic alteration of small B LYMPHOCYTES or T LYMPHOCYTES in culture into large blast-like cells able to synthesize DNA and RNA and to divide mitotically. It is induced by INTERLEUKINS; MITOGENS such as PHYTOHEMAGGLUTININS, and by specific ANTIGENS. It may also occur in vivo as in GRAFT REJECTION.
Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing HEMOGLOBIN whose function is to transport OXYGEN.
Suspensions of attenuated or killed viruses administered for the prevention or treatment of infectious viral disease.
White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B (with subpopulations of each), or NATURAL KILLER CELLS.
A technique that combines protein electrophoresis and double immunodiffusion. In this procedure proteins are first separated by gel electrophoresis (usually agarose), then made visible by immunodiffusion of specific antibodies. A distinct elliptical precipitin arc results for each protein detectable by the antisera.
Microscopy using an electron beam, instead of light, to visualize the sample, thereby allowing much greater magnification. The interactions of ELECTRONS with specimens are used to provide information about the fine structure of that specimen. In TRANSMISSION ELECTRON MICROSCOPY the reactions of the electrons that are transmitted through the specimen are imaged. In SCANNING ELECTRON MICROSCOPY an electron beam falls at a non-normal angle on the specimen and the image is derived from the reactions occurring above the plane of the specimen.
An immunoglobulin associated with MAST CELLS. Overexpression has been associated with allergic hypersensitivity (HYPERSENSITIVITY, IMMEDIATE).
Antigenic determinants recognized and bound by the B-cell receptor. Epitopes recognized by the B-cell receptor are located on the surface of the antigen.
Polypeptide chains, consisting of 211 to 217 amino acid residues and having a molecular weight of approximately 22 kDa. There are two major types of light chains, kappa and lambda. Two Ig light chains and two Ig heavy chains (IMMUNOGLOBULIN HEAVY CHAINS) make one immunoglobulin molecule.
The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.
Tests that are dependent on the clumping of cells, microorganisms, or particles when mixed with specific antiserum. (From Stedman, 26th ed)
Small synthetic peptides that mimic surface antigens of pathogens and are immunogenic, or vaccines manufactured with the aid of recombinant DNA techniques. The latter vaccines may also be whole viruses whose nucleic acids have been modified.
Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection.
Any of various animals that constitute the family Suidae and comprise stout-bodied, short-legged omnivorous mammals with thick skin, usually covered with coarse bristles, a rather long mobile snout, and small tail. Included are the genera Babyrousa, Phacochoerus (wart hogs), and Sus, the latter containing the domestic pig (see SUS SCROFA).
Microscopy in which the samples are first stained immunocytochemically and then examined using an electron microscope. Immunoelectron microscopy is used extensively in diagnostic virology as part of very sensitive immunoassays.
The type species of LENTIVIRUS and the etiologic agent of AIDS. It is characterized by its cytopathic effect and affinity for the T4-lymphocyte.
Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
Semisynthetic conjugates of various toxic molecules, including RADIOACTIVE ISOTOPES and bacterial or plant toxins, with specific immune substances such as IMMUNOGLOBULINS; MONOCLONAL ANTIBODIES; and ANTIGENS. The antitumor or antiviral immune substance carries the toxin to the tumor or infected cell where the toxin exerts its poisonous effect.
The presence of antibodies directed against phospholipids (ANTIBODIES, ANTIPHOSPHOLIPID). The condition is associated with a variety of diseases, notably systemic lupus erythematosus and other connective tissue diseases, thrombopenia, and arterial or venous thromboses. In pregnancy it can cause abortion. Of the phospholipids, the cardiolipins show markedly elevated levels of anticardiolipin antibodies (ANTIBODIES, ANTICARDIOLIPIN). Present also are high levels of lupus anticoagulant (LUPUS COAGULATION INHIBITOR).
Use of radiolabeled antibodies for diagnostic imaging of neoplasms. Antitumor antibodies are labeled with diverse radionuclides including iodine-131, iodine-123, indium-111, or technetium-99m and injected into the patient. Images are obtained by a scintillation camera.
Common name for the species Gallus gallus, the domestic fowl, in the family Phasianidae, order GALLIFORMES. It is descended from the red jungle fowl of SOUTHEAST ASIA.
A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.
External envelope protein of the human immunodeficiency virus which is encoded by the HIV env gene. It has a molecular weight of 120 kDa and contains numerous glycosylation sites. Gp120 binds to cells expressing CD4 cell-surface antigens, most notably T4-lymphocytes and monocytes/macrophages. Gp120 has been shown to interfere with the normal function of CD4 and is at least partly responsible for the cytopathic effect of HIV.
Adherence of cells to surfaces or to other cells.
A 44-kDa highly glycosylated plasma protein that binds phospholipids including CARDIOLIPIN; APOLIPOPROTEIN E RECEPTOR; membrane phospholipids, and other anionic phospholipid-containing moieties. It plays a role in coagulation and apoptotic processes. Formerly known as apolipoprotein H, it is an autoantigen in patients with ANTIPHOSPHOLIPID ANTIBODIES.
A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).
The principle immunoglobulin in exocrine secretions such as milk, respiratory and intestinal mucin, saliva and tears. The complete molecule (around 400 kD) is composed of two four-chain units of IMMUNOGLOBULIN A, one SECRETORY COMPONENT and one J chain (IMMUNOGLOBULIN J-CHAINS).
A form of fluorescent antibody technique utilizing a fluorochrome conjugated to an antibody, which is added directly to a tissue or cell suspension for the detection of a specific antigen. (Bennington, Saunders Dictionary & Encyclopedia of Laboratory Medicine and Technology, 1984)
The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).
Substances that augment, stimulate, activate, potentiate, or modulate the immune response at either the cellular or humoral level. The classical agents (Freund's adjuvant, BCG, Corynebacterium parvum, et al.) contain bacterial antigens. Some are endogenous (e.g., histamine, interferon, transfer factor, tuftsin, interleukin-1). Their mode of action is either non-specific, resulting in increased immune responsiveness to a wide variety of antigens, or antigen-specific, i.e., affecting a restricted type of immune response to a narrow group of antigens. The therapeutic efficacy of many biological response modifiers is related to their antigen-specific immunoadjuvanticity.
Proteins found in any species of bacterium.
Any of numerous agile, hollow-horned RUMINANTS of the genus Capra, in the family Bovidae, closely related to the SHEEP.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
Antibodies found in adult RHEUMATOID ARTHRITIS patients that are directed against GAMMA-CHAIN IMMUNOGLOBULINS.
Antibody-mediated immune response. Humoral immunity is brought about by ANTIBODY FORMATION, resulting from TH2 CELLS activating B-LYMPHOCYTES, followed by COMPLEMENT ACTIVATION.
Any immunization following a primary immunization and involving exposure to the same or a closely related antigen.
Proteins isolated from the outer membrane of Gram-negative bacteria.
Proteins found in any species of virus.
The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH.
Crystallizable fragments composed of the carboxy-terminal halves of both IMMUNOGLOBULIN HEAVY CHAINS linked to each other by disulfide bonds. Fc fragments contain the carboxy-terminal parts of the heavy chain constant regions that are responsible for the effector functions of an immunoglobulin (COMPLEMENT fixation, binding to the cell membrane via FC RECEPTORS, and placental transport). This fragment can be obtained by digestion of immunoglobulins with the proteolytic enzyme PAPAIN.
In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.
Any of the ruminant mammals with curved horns in the genus Ovis, family Bovidae. They possess lachrymal grooves and interdigital glands, which are absent in GOATS.
Proteins found in any species of protozoan.
Mutant mice homozygous for the recessive gene "nude" which fail to develop a thymus. They are useful in tumor studies and studies on immune responses.
A cell line derived from cultured tumor cells.
Molecules found on the surface of some, but not all, B-lymphocytes, T-lymphocytes, and macrophages, which recognize and combine with the Fc (crystallizable) portion of immunoglobulin molecules.
Manifestations of the immune response which are mediated by antigen-sensitized T-lymphocytes via lymphokines or direct cytotoxicity. This takes place in the absence of circulating antibody or where antibody plays a subordinate role.
Transport proteins that carry specific substances in the blood or across cell membranes.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
Proteins that bind to particles and cells to increase susceptibility to PHAGOCYTOSIS, especially ANTIBODIES bound to EPITOPES that attach to FC RECEPTORS. COMPLEMENT C3B may also participate.
Unstable isotopes of indium that decay or disintegrate emitting radiation. In atoms with atomic weights 106-112, 113m, 114, and 116-124 are radioactive indium isotopes.
Cells of the lymphoid series that can react with antigen to produce specific cell products called antibodies. Various cell subpopulations, often B-lymphocytes, can be defined, based on the different classes of immunoglobulins that they synthesize.
The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.
The marking of biological material with a dye or other reagent for the purpose of identifying and quantitating components of tissues, cells or their extracts.
A subclass of ACIDIC GLYCOSPHINGOLIPIDS. They contain one or more sialic acid (N-ACETYLNEURAMINIC ACID) residues. Using the Svennerholm system of abbrevations, gangliosides are designated G for ganglioside, plus subscript M, D, or T for mono-, di-, or trisialo, respectively, the subscript letter being followed by a subscript arabic numeral to indicated sequence of migration in thin-layer chromatograms. (From Oxford Dictionary of Biochemistry and Molecular Biology, 1997)
Lipid-containing polysaccharides which are endotoxins and important group-specific antigens. They are often derived from the cell wall of gram-negative bacteria and induce immunoglobulin secretion. The lipopolysaccharide molecule consists of three parts: LIPID A, core polysaccharide, and O-specific chains (O ANTIGENS). When derived from Escherichia coli, lipopolysaccharides serve as polyclonal B-cell mitogens commonly used in laboratory immunology. (From Dorland, 28th ed)
Studies determining the effectiveness or value of processes, personnel, and equipment, or the material on conducting such studies. For drugs and devices, CLINICAL TRIALS AS TOPIC; DRUG EVALUATION; and DRUG EVALUATION, PRECLINICAL are available.
Procedures by which protein structure and function are changed or created in vitro by altering existing or synthesizing new structural genes that direct the synthesis of proteins with sought-after properties. Such procedures may include the design of MOLECULAR MODELS of proteins using COMPUTER GRAPHICS or other molecular modeling techniques; site-specific mutagenesis (MUTAGENESIS, SITE-SPECIFIC) of existing genes; and DIRECTED MOLECULAR EVOLUTION techniques to create new genes.
A method to identify and enumerate cells that are synthesizing ANTIBODIES against ANTIGENS or HAPTENS conjugated to sheep RED BLOOD CELLS. The sheep red blood cells surrounding cells secreting antibody are lysed by added COMPLEMENT producing a clear zone of HEMOLYSIS. (From Illustrated Dictionary of Immunology, 3rd ed)
Cell surface proteins that bind signalling molecules external to the cell with high affinity and convert this extracellular event into one or more intracellular signals that alter the behavior of the target cell (From Alberts, Molecular Biology of the Cell, 2nd ed, pp693-5). Cell surface receptors, unlike enzymes, do not chemically alter their ligands.
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
Sensitive assay using radiolabeled ANTIGENS to detect specific ANTIBODIES in SERUM. The antigens are allowed to react with the serum and then precipitated using a special reagent such as PROTEIN A sepharose beads. The bound radiolabeled immunoprecipitate is then commonly analyzed by gel electrophoresis.
The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.)
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
Diseases of domestic cattle of the genus Bos. It includes diseases of cows, yaks, and zebus.
Ruminant mammals of South America. They are related to camels.
Measurable and quantifiable biological parameters (e.g., specific enzyme concentration, specific hormone concentration, specific gene phenotype distribution in a population, presence of biological substances) which serve as indices for health- and physiology-related assessments, such as disease risk, psychiatric disorders, environmental exposure and its effects, disease diagnosis, metabolic processes, substance abuse, pregnancy, cell line development, epidemiologic studies, etc.
The phenomenon of target cell destruction by immunologically active effector cells. It may be brought about directly by sensitized T-lymphocytes or by lymphoid or myeloid "killer" cells, or it may be mediated by cytotoxic antibody, cytotoxic factor released by lymphoid cells, or complement.
Unglycosylated phosphoproteins expressed only on B-cells. They are regulators of transmembrane Ca2+ conductance and thought to play a role in B-cell activation and proliferation.
The type (and only) species of RUBIVIRUS causing acute infection in humans, primarily children and young adults. Humans are the only natural host. A live, attenuated vaccine is available for prophylaxis.
The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.
CELL LINE derived from the ovary of the Chinese hamster, Cricetulus griseus (CRICETULUS). The species is a favorite for cytogenetic studies because of its small chromosome number. The cell line has provided model systems for the study of genetic alterations in cultured mammalian cells.
Microscopy of specimens stained with fluorescent dye (usually fluorescein isothiocyanate) or of naturally fluorescent materials, which emit light when exposed to ultraviolet or blue light. Immunofluorescence microscopy utilizes antibodies that are labeled with fluorescent dye.
A biosensing technique in which biomolecules capable of binding to specific analytes or ligands are first immobilized on one side of a metallic film. Light is then focused on the opposite side of the film to excite the surface plasmons, that is, the oscillations of free electrons propagating along the film's surface. The refractive index of light reflecting off this surface is measured. When the immobilized biomolecules are bound by their ligands, an alteration in surface plasmons on the opposite side of the film is created which is directly proportional to the change in bound, or adsorbed, mass. Binding is measured by changes in the refractive index. The technique is used to study biomolecular interactions, such as antigen-antibody binding.

Small antibody-like proteins with prescribed ligand specificities derived from the lipocalin fold. (1/137)

We demonstrate that the ligand pocket of a lipocalin from Pieris brassicae, the bilin-binding protein (BBP), can be reshaped by combinatorial protein design such that it recognizes fluorescein, an established immunological hapten. For this purpose 16 residues at the center of the binding site, which is formed by four loops on top of an eight-stranded beta-barrel, were subjected to random mutagenesis. Fluorescein-binding BBP variants were then selected from the mutant library by bacterial phage display. Three variants were identified that complex fluorescein with high affinity, exhibiting dissociation constants as low as 35.2 nM. Notably, one of these variants effects almost complete quenching of the ligand fluorescence, similarly as an anti-fluorescein antibody. Detailed ligand-binding studies and site-directed mutagenesis experiments indicated (i) that the molecular recognition of fluorescein is specific and (ii) that charged residues at the center of the pocket are responsible for tight complex formation. Sequence comparison of the BBP variants directed against fluorescein with the wild-type protein and with further variants that were selected against several other ligands revealed that all of the randomized amino acid positions are variable. Hence, a lipocalin can be used for generating molecular pockets with a diversity of shapes. We term this class of engineered proteins "anticalins." Their one-domain scaffold makes them a promising alternative to antibodies to create a stable receptor protein for a ligand of choice.  (+info)

Efficient screening for catalytic antibodies using a short transition-state analog and detailed characterization of selected antibodies. (2/137)

One of the major obstacles to acquiring catalytic antibodies is that it requires labor-intensive procedures to select catalytic antibodies from huge repertories of antibodies. Here, we selected potential catalytic Abs by utilizing their affinity towards a short transition-state analog which contained only the transition-state structural element, and evaluated in detail its efficiency to enrich catalytic Abs. Hybridoma supernatants elicited against a phosphonate derivative, the TSA1, were screened by a three-step screening process: step 1, ELISA for TSA1-BSA; step 2, ELISA for the short TSA4; and step 3, competitive-inhibition by the short TSA2. Only 22. 8% of positive mAbs from step 1 were found to be catalytic. The rate of catalytic Abs increased to 45.7% using screening steps 1 plus 2, and reached 83.3% using all three screening steps. This clearly suggests that our screening protocol is an efficient method to select potential catalytic Abs. Furthermore, we characterized the properties of both the catalytic Abs and the noncatalytic Abs in detail. The catalytic Abs tended to have lower Kd for TSA1 and the short TSA2 than noncatalytic Abs. It was also observed that catalytic Abs showed clear enantiospecificity toward substrate 6 containing d-phenylalanine while noncatalytic Abs did not. The detailed analysis of kinetic and binding parameters for these antibodies gives us further insight into catalytic antibodies.  (+info)

Diverse structural solutions to catalysis in a family of antibodies. (3/137)

BACKGROUND: Small organic molecules coupled to a carrier protein elicit an antibody response on immunisation. The diversity of this response has been found to be very narrow in several cases. Some antibodies also catalyse chemical reactions. Such catalytic antibodies are usually identified among those that bind tightly to an analogue of the transition state (TSA) of the relevant reaction; therefore, catalytic antibodies are also thought to have restricted diversity. To further characterise this diversity, we investigated the structure and biochemistry of the catalytic antibody 7C8, one of the most efficient of those which enhance the hydrolysis of chloramphenicol esters, and compared it to the other catalytic antibodies elicited in the same immunisation. RESULTS: The structure of a complex of the 7C8 antibody Fab fragment with the hapten TSA used to elicit it was determined at 2.2 A resolution. Structural comparison with another catalytic antibody (6D9) raised against the same hapten revealed that the two antibodies use different binding modes. Furthermore, whereas 6D9 catalyses hydrolysis solely by transition-state stabilisation, data on 7C8 show that the two antibodies use mechanisms where the catalytic residue, substrate specificity and rate-limiting step differ. CONCLUSIONS: Our results demonstrate that substantial diversity may be present among antibodies catalysing the same reaction. Therefore, some of these antibodies represent different starting points for mutagenesis aimed at boosting their activity. This increases the chance of obtaining more proficient catalysts and provides opportunities for tailoring catalysts with different specificities.  (+info)

Evolution of shape complementarity and catalytic efficiency from a primordial antibody template. (4/137)

The crystal structure of an efficient Diels-Alder antibody catalyst at 1.9 angstrom resolution reveals almost perfect shape complementarity with its transition state analog. Comparison with highly related progesterone and Diels-Alderase antibodies that arose from the same primordial germ line template shows the relatively subtle mutational steps that were able to evolve both structural complementarity and catalytic efficiency.  (+info)

A general kinetic approach to investigation of active-site availability in macromolecular catalysts. (5/137)

A potentially general kinetic method for the investigation of active-site availability in preparations of macromolecular catalysts was developed. Three kinetic models were considered: (a) the conventional two-step model of enzyme catalysis, where the preparation contains only active catalyst (E(a)) and inert (i.e. non-binding, non-catalytic) material (E(i)); (b) an extension of the conventional model (a) involving only E(a) and E(i), but with non-productive binding to E(a) (in addition to productive binding); (c) a model in which the preparation contains also binding but non-catalytic material (E(b)), predicted to be present in polyclonal catalytic antibody preparations. The method involves comparing the parameters V(max) and K(m) obtained under catalytic conditions where substrate concentrations greatly exceed catalyst concentration with those (klim/obs, the limiting value of the first-order rate constant, k(obs), at saturating concentrations of catalyst; and Kapp/m) for single-turnover kinetics, in which the reverse situation obtains. The active-site contents of systems that adhere to model (a) or extensions that also lack E(b), such as the non-productive binding model (b), may be calculated using [E(a)](T)=V(max)/klim/obs. This was validated by showing that, for alpha-chymotrypsin, identical values of [E(a)](T) were obtained by the kinetic method using Suc-Ala-Ala-Pro-Phe-4-nitroanilide as substrate and the well-known 'all-or-none' spectroscopic assay using N-trans-cinnamoylimidazole as titrant. For systems that contain E(b), such as polyclonal catalytic antibody preparations, V(max)/klim/obs is more complex, but provides an upper limit to [E(a)](T). Use of the kinetic method to investigate PCA 271-22, a polyclonal catalytic antibody preparation obtained from the antiserum of sheep 271 in week 22 of the immunization protocol, established that [E(a)](T) is less than approx. 8% of [IgG], and probably less than approx. 1% of [IgG].  (+info)

Cyclic peptide formation catalyzed by an antibody ligase. (6/137)

Cyclic hexapeptides represent a class of compounds with important, diverse biological activities. We report herein that the antibody 16G3 catalyzes the cyclization of d-Trp-Gly-Pal-Pro-Gly-Phe small middle dotp-nitrophenyl ester (8a) to give c-(d-Trp-Gly-Pal-Pro-Gly-l-Phe) (11a). The antibody does not, however, catalyze either epimerization or hydrolysis. The resulting rate enhancement of the cyclization by 16G3 (22-fold) was sufficient to form the desired product in greater than 90% yield. In absolute rate terms, the turnover of 16G3 is estimated to be 2 min(-1). The background rate of epimerization of 8a was reduced from 10 to 1% and hydrolysis from 50 to 4% in the presence of 16G3. As expected, the catalytic effects of 16G3 were blocked by the addition of an amount of the hapten equal to twice the antibody concentration. We also synthesized three diastereomers of 8a: the d-Trp(1)-d-Phe(6) (8b), l-Trp(1)-l-Phe(6) (8c), and l-Trp(1)-d-Phe(6) (8d) hexapeptides as well as d-Trp'-l-Trp(6) (12) and d-Phe'-l-Phe(6) (13). As expected, the rate enhancement by 16G3 was greatest for 8a, because the stereochemistry of Trp(1) and Phe(6) matches that of the corresponding residues on the hapten used to induce the biosynthesis of 16G3. A model of the variable domain of 16G3 was generated from the primary sequence using the antibody structural database to guide the model construction. The resulting model provided support for some previously proposed interpretations of the kinetic data, while providing valuable new insights for others.  (+info)

Mechanism of an antibody-catalysed allylic isomerization. (7/137)

The catalytic antibody 4B2, which was generated against a substituted amidine 1, catalyses the allylic isomerization of beta, gamma-unsaturated ketones with an acceleration factor (k(cat)/k(uncat)) of 1.5x10(3). On the basis of the 'bait and switch' strategy, it was reasoned that the positively charged hapten could elicit, by charge complementarity, an acidic residue (Asp or Glu) in the antibody-binding site in the right position to catalyse this proton transfer reaction. The pH dependence curve of k(cat)/K(m) shows a bell-shaped feature with an optimum at approx. pH 4.5. By cloning and sequencing the light and heavy chains of the 4B2 antibody, we confirmed the presence of several Asp and Glu residues in the complementarity-determining region loops. The antibody catalyses the alpha-proton exchange on the same substrates, demonstrating the involvement of a dienol intermediate in the reaction mechanism. Kinetic studies with (2)H-NMR provide evidence that alpha-proton abstraction is stereospecific. Whether the process involves one or two acid/base residues in this simple proton transfer or whether it is a concerted mechanism is discussed.  (+info)

Using antibody catalysis to study the outcome of multiple evolutionary trials of a chemical task. (8/137)

Catalytic aldolase antibodies generated by immunization with two different, but structurally related, beta-diketone haptens were cloned and sequenced to study similarities and differences between independently evolved catalysts. Kinetic and sequence analysis coupled with mutagenesis, structural, and modeling studies reveal that the defining event in the evolution of these catalysts was a somatic mutation that placed a lysine residue in a deep, yet otherwise unrefined, hydrophobic pocket. We suggest that covalent chemistries may be as readily selected from the immune repertoire as the traditional noncovalent interactions that have formed the basis of immunochemistry until this time. Further, we believe that these experiments recapitulate the defining events in the evolution of nature's enzymes, particularly as they relate to chemical mechanism, catalytic promiscuity, and gene duplication.  (+info)

The present invention relates to catalytic antibodies and a method for producing the same wherein a host is immunized using an antigen chelate or more specifically a stable compound capable of chelating metal ions. The immune response mounted in response to the antigen chelate produces antibodies that are capable of binding both a substrate and a metal ion, thus achieving a metal cofactor assisted reaction.
TY - JOUR. T1 - Catalytic antibodies. AU - Benkovic, Stephen. PY - 1992/1/1. Y1 - 1992/1/1. UR - UR - U2 - 10.1146/ DO - 10.1146/ M3 - Review article. C2 - 1497313. AN - SCOPUS:0026717963. VL - 61. SP - 29. EP - 54. JO - Annual Review of Biochemistry. JF - Annual Review of Biochemistry. SN - 0066-4154. ER - ...
TY - JOUR. T1 - Crystal structure of a glycosylated Fab from an IgM cryoglobulin with properties of a natural proteolytic antibody. AU - Ramsland, Paul A.. AU - Terzyan, Simon S.. AU - Cloud, Gwendolyn. AU - Bourne, Christina R.. AU - Farrugia, William. AU - Tribbick, Gordon. AU - Geysen, H. Mario. AU - Moomaw, Carolyn R.. AU - Slaughter, Clive A.. AU - Edmundson, Allen B.. N1 - Copyright: Copyright 2008 Elsevier B.V., All rights reserved.. PY - 2006/5/1. Y1 - 2006/5/1. N2 - The 2.6 Å (1 Å = 0.1 nm) resolution structure has been determined for the glycosylated Fab (fragment antigen binding) of an IgM (Yvo) obtained from a subject with Waldenströms macroglobulinaemia. Dynamic light scattering was used to estimate the gel point and monitor the formation of an ordered hydroscopic gel of Yvo IgM upon cooling. If a cryoglobulin forms gels in peripheral tissues and organs, the associated swelling and damage to microvasculature can result in considerable morbidity and mortality. The ...
1KNO: Crystal structure of the complex of a catalytic antibody Fab fragment with a transition state analog: structural similarities in esterase-like catalytic antibodies.
TY - JOUR. T1 - A light-activated antibody catalyst. AU - Yli-Kauhaluoma, Jari. AU - Taylor, Matthew. AU - Hoffman, Timothy. AU - Lerner, Richard. AU - Janda, Kim. PY - 1998. Y1 - 1998. N2 - A catalytic antibody for a multistep Norrish type II photochemical reaction was investigated. Absorption of light energy by α-ketoamide substrate 1b produced a high-energy biradical intermediate, that was then directed by the antibody microenvironment to form tetrahydropyrazine 13 with a kcat of 1.4 × 10-3 min-1 at 280 nm irradiation and an enantiomeric excess of 78%. Antibody-catalyzed reactions performed with radiolabeled substrate indicated that little self-inactivation (6.8 mol % covalent modification after four turnovers per antibody) occurred. The singular product obtained in the antibody-catalyzed reaction was not observed in the uncatalyzed reaction unless the pH was lowered below 4. Studies suggested that the interplay of conformational control and chemical catalysis were responsible for the high ...
Antibodies were raised to a 1-benzazepine hapten (I) and the properties of 2 of the strongly binding clones, designated C3 and C5, as catalysts examd. Neither antibody catalyzed the reaction for which they were first generated, electrophilic substitution in the benzene ring, but C3 catalyzed the hydrolysis of an aralkyl 4-nitrophenyl ester with a rate enhancement of ,106 compared with the background solvolysis rate. The mechanism of the hydrolysis reaction seems to involve general base catalysis on the basis of chem. modification expts. and isotope effects on the reaction rate in D2O. The possibility that C3 might catalyze other reactions (elimination, deuterium exchange, and epoxide opening) was investigated but no other reactions were obsd. In contrast, C5 catalyzed none of the reactions investigated. The properties of the 2 antibodies are discussed with respect to their ability to bind compds. structurally related to the hapten.. ...
Antibody 7A1 hydrolyzes cocaine to produce nonpsychoactive metabolites ecgonine methyl ester and benzoic acid. Crystal structures of 7A1 Fab and six complexes with substrate cocaine, the transition state analog, products ecgonine methyl ester and benzoic acid together and individually, as well as h …
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TY - JOUR. T1 - Blood-Derived RNA- and microRNA-Hydrolyzing IgG Antibodies in Schizophrenia Patients. AU - Ermakov, E. A.. AU - Ivanova, S. A.. AU - Buneva, V. N.. AU - Nevinsky, G. A.. PY - 2018/5/1. Y1 - 2018/5/1. N2 - Abzymes with various catalytic activities are the earliest statistically significant markers of existing and developing autoimmune diseases (AIDs). Currently, schizophrenia (SCZD) is not considered to be a typical AID. It was demonstrated recently that antibodies from SCZD patients efficiently hydrolyze DNA and myelin basic protein. Here, we showed for the first time that autoantibodies from 35 SCZD patients efficiently hydrolyze RNA (cCMP , poly(C) , poly(A) , yeast RNA) and analyzed site-specific hydrolysis of microRNAs involved in the regulation of several genes in SCZD (miR-137, miR-9-5p, miR-219-2-3p, and miR-219a-5p). All four microRNAs were cleaved by IgG preparations (n = 21) from SCZD patients in a site-specific manner. The RNase activity of the abzymes correlated with ...
Examines monoclonal antibody synthesis. Discusses expression of MABs in various mammalian systems. Includes a review of research on the expression of antibody fragments in various microbial systems. Describes the use of catalytic antibodies for a variety of applications. Reviews applications of MABs and its fragments.
DESCRIPTION (provided by applicant): Antibodies and their fragments that specifically break down proteins and peptides are found in an autoimmune context, in multiple myeloma and in certain experimental immune responses elicited against viral polypeptides. Studies support the premise that antibodies with catalytic activity are inherent to the immune repertoire, but may be excluded from dominant responses in the healthy immune subject. Two approaches are described that could lead to production of efficient serine protease-like catalytic antibodies. A new method of immunization is proposed to specifically elicit antibodies that utilize covalent reactivity in antigen binding. Antibodies induced in the covalent immunization procedure will be characterized for hydrolytic activity against defined peptide analogs. Differences in the covalent immunization responses in normal and autoimmune mice will be investigated to reveal possible mechanisms of its regulation. Alternatively, covalent binding will be ...
Scripps, which holds an undisclosed royalty interest and equity stake in CovX, stands to receive a percentage of the proceeds from the sale and royalties from any resulting therapies based on the companys catalytic antibody technology - which could eventually rival the multi-billion dollar therapeutic monoclonal antibody market, company officials said.
The structures of AmpC beta-lactamase from Escherichia coli, alone and in complex with a transition-state analogue, have been determined by X-ray crystallography. The native enzyme was determined to 2.0 A resolution, and the structure with the transition-state analogue m-aminophenylboronic acid was …
Sigma-Aldrich offers abstracts and full-text articles by [Elizabeth Buck, Zhiguo Jake Song, David Tschaen, Peter G Dormer, R P Volante, Paul J Reider].
The Versatile Binding Mode of Transition-State Analogue Inhibitors of Tyrosinase towards Dicopper(II) Model Complexes: Experimental and Theoretical Investigations., Orio, Maylis, Bochot Constance, Dubois Carole, Gellon Gisèle, Hardre Renaud, Jamet Hélène, Luneau Dominique, Philouze Christian, Reglier Marius, Serratrice Guy, et al. , Chem. - A Eur. J., Volume 17, Number 48, p.13482-13494, S13482/1-S13482/19, (2011) ...
Binge drinking is the largest contributor to the high cost of alcohol use, according to the CDC. Binge drinking is defined by the National Institute on Alcohol Abuse and Alcoholism as consuming enough alcohol in the span of two hours that blood alcohol concentration levels reach about 0.08g/dL. This comes out to about four drinks in two hours for women, and about five drinks in two hours for men, although this can vary depending on several factors, including body weight, type of drink consumed and whether food and water are also consumed. Binge drinking is responsible for nearly two-thirds of all alcohol-related fatalities (killing 80,000 people per year), and accounts for about $171 billion, or about 70 percent, of alcohols total cost to the U.S. economy. The high cost of binge drinking really isnt such a surprise. Nearly 38 million Americans, including many college students and underage users, participate in binge drinking, with most reporting a binge drinking session at least four times per ...
This work describes a selective and specific sample preparation workflows and superior chromatographic separation of mAb subunit light chains.
The Diels-Alder reaction is one of the most powerful synthetic tools in organic chemistry, and asymmetric Diels-Alder catalysis allows for rapid construction of chiral carbon scaffolds. For this reason, considerable effort has been invested in developing efficient and stereoselective organo- and biocatalysts. However, Diels-Alder is a virtually unknown reaction in Nature, and to engineer an enzyme into a Diels-Alderase is therefore a challenging task. Despite several successful designs of catalytic antibodies since the 1980s, their catalytic activities have remained low, and no true artificial Diels-Alderase enzyme was reported before 2010.. In this thesis, we employ state-of-the-art computational tools to study the mechanism of organocatalyzed Diels-Alder in detail, and to redesign existing enzymes into intermolecular Diels-Alder catalysts. Papers I-IV explore the mechanistic variations when employing increasingly activated reactants and the effect of catalysis. In particular, the ...
Shop Fructose-1,6-/sedoheptulose-1,7-bisphosphate aldolase ELISA Kit, Recombinant Protein and Fructose-1,6-/sedoheptulose-1,7-bisphosphate aldolase Antibody at MyBioSource. Custom ELISA Kit, Recombinant Protein and Antibody are available.
In this study, we used a phenotypic whole-cell selection approach to identify serotype-independent mAbs that mediated OPK activity against P. aeruginosa and inhibited attachment to epithelial cells. The most active antibody in both the OPK and cell attachments assays described in this study, Cam-003, was also shown to be prophylactically protective in three distinct clinically relevant P. aeruginosa murine infection models: pneumonia, thermal injury, and ocular keratitis, which emphasizes the different aspects of opportunistic P. aeruginosa infections. Although whole-cell phage panning approaches have previously been attempted in the identification of mAbs that bind other microorganisms and cancer cells (Reiche et al., 2002; Zou et al., 2007; Beerli et al., 2008; Fukuchi et al., 2010), this is the first example using this approach with both healthy subject and convalescent patient donors in combination with mechanistic activity screening and target identification for a bacterial pathogen. All ...
Rabbit light chain 3315, prepared from a homogeneous antipneumococcal antibody, was subjected to hydrolysis by pepsin without prior reduction and alkylation of the intrachain disulfide bonds. Gel filtration of the hydrolysate on Sephadex G-10, G-15, and G-25 and ion exchange chromatography on SP-Sephadex yielded several disulfide bridge peptides. These were fully reduced and alkylated and sequenced by Edman degradation. The peptides were located in the light chain sequence determined in independent studies from our laboratory.. The half-cystine residues in this κB rabbit chain are located at positions 23, 80, 88, 134, 171, 194, and 214. The extra disulfide bridge extends between residues 80 and 171, thus joining the variable and constant domains. This is consistent with x-ray diffraction crystallographic studies showing that the corresponding residues in human light chains are separated by a distance compatible with disulfide bond formation.. ...
Korean heritage; majors in chemistry at Cornell University; works as an undergraduate research assistant in the George P. Hess laboratory; enters the Medical Scientist Training Program at Stanford University; focus on proteins and protein folding; pulse-labeling proteins with Robert L. Baldwin; studying synthetic peptides; catalytic antibody research; scientists need to communicate with laypeople; interest in developing pharmaceuticals; establishes a lab at the Whitehead Institute for Biomedical Research; develops a peptide model of a protein folding intermediate; Terrence G. Oas; research on leucine zippers and coiled coils; viral fusion proteins; the therapeutic potential of peptides; the funding of scientific research; teaching; developing computational methods to predict protein folding structures; effects of computer modeling on structural biology; involvement in biotechnology companies; David Baltimore; the investigation of scientific fraud ...
It is known that intranuclear histones can be pernicious after entering to the extracellular space. In addition, the immunization of animals with exogenous histones leads to systemic inflammatory and toxic reactions. Abzymes—autoantibodies with enzymatic activities—are the distinctive feature of autoimmune diseases and they can be especially dangerous to humans. Here, electrophoretically homogeneous IgGs were isolated from sera of patients with multiple sclerosis (MS) by chromatography on several affinity sorbents. We present evidence that sera of all MS patients contain autoantibodies against histones and 73% of IgGs purified from the sera of 59 MS patients efficiently hydrolyze from one to five histones: H1, H2a, H2b, H3, and H4. The relative average efficiency of the histones hydrolysis was ~3.9-fold higher than that for healthy donors. The relative average activity of IgGs depends on the type of MS and decreased approximately in the following order: debut of MS, secondary progressive
antibodies is available. The Achilles heel, a tiny stretch of ... can generate abzymes to the Achilles heel of HIV. The human ... sequence that resembles the Achilles heel can explain the production ...
The present invention utilizes two monoclonal antibodies, 679 and hMN14, and two point mutations of 679, (679-VH (I3Q) and 679-VK(C101S)), to produce antigen specific diabodies. In addition, a bispecific diabody is produced from hMN14 and h679, which is obtained by grafting the CDRs of 679 onto a framework of amino acid residues found in human antibodies. The murine monoclonal antibody designated 679 (an IgGl, K) binds with high affinity to molecules containing the moiety histamine-succinyl-glycyl (HSG) (Morel etal, Molecular Immunology, 22, 995-1000, 1990). The nucleotide sequence pertaining to the variable domains (VH and VK) of 679 has been determined (Qu et al., unpublished results). VK is one of two isotypes of the antibody light chains, Vu As depicted in Figure 1, the design of the gene construct (679-scFv-L5) for expressing a 679 diabody possesses the following features: 1) The carboxyl terminal end of VH is linked to the amino terminal end of VK by the peptide linker Gly-Gly-Gly-Gly-Ser ...
2 questions: myeloma cell lines and mice MABs - posted in Immunology: Dear all, I wanted to post a couple of unrelated questions. I hope someone with more experience can answer them. 1) Is there any advantage/disadvantage in using either NSO or NS-1 myeloma cells for making hybridomas? I have read that NS-1 cells actually produce a non-secreted version of a antibody light chain. However, many labs seem to be using NS-1 for fusion. Are these cells really harmless for monoclonal antibodies?...
Zn(II)-dependent glutaminyl cyclase (QC) converts N-terminal glutamine or glutamate residues of peptides and proteins. The reaction product is in both cases N-terminal pyroglutamic acid (pyroGlu). In animals the glutaminyl cyclization is involved in posttranslational modification and activation of peptide-based hormone and chemokine precursors. Recently it was established that the driving force in neurodegenerative processes is the pyroGlu modification at the N-terminus of Aβ peptides processed by QC. This unveils the inhibition of QC as a strategy in AD treatment. The enzyme-specific inhibition is required in order to avoid noxious side effects. The elucidation of the reaction mechanism might make possible the development of mechanism-based QC inhibitors (e.g. transition-state analog compounds). Mechanistic and structural investigations were accomplished using the mitochondrial isoform of QC from Drosophila melanogaster. Regarding enzyme kinetic and structural properties, this enzyme is highly ...
Mannonojiritetrazole (7), a novel mannosidase inhibitor, has been synthesized in six steps from 2,3,4,6-tetra-O-benzyl-D-mannose oxime. The structure of 7 has been established by X-ray analysis. The solid state conformation of 7 is H-6(7) (=H-4(3), numbering based on carbohydrate nomenclature), and the conformation in CD3OD is close to S-7 (sofa; = S-3, numbering based upon carbohydrate nomenclature), while the conformation of the previously synthesized analogue with the gluco configuration (6) is H-6(7), both in the solid state and in solution in D2O or CD3OD. Both 6 and 7 have been tested as inhibitors of each of a series of five alpha- and beta-glucosidases and -mannosidases as well as of a beta-galactosidase, and inhibition constants have been determined. A good correlation (p = 0.9) was found between log K-i for each inhibitor-enzyme pair and log (V-m/K-m) for the corresponding substrate-enzyme pair, thereby providing the first such proof for any glycosidase inhibitor being a transition ...
1IEL: Structures of ceftazidime and its transition-state analogue in complex with AmpC beta-lactamase: implications for resistance mutations and inhibitor design.
to the similar functions with natural enzymes, maturing preparation methods and other advantages compared with natural enzymes. In order to know well about the prodrug activation mediated by MEMs, the cases of practical and potential prodrug activation are listed in Table 2. Although the perfect examples for practical prodrug activation are relative less, ones for potential prodrug activation are more and inspiring. The potential prodrug activation can be classified into two types. In type I, the true MEMs should be completed by loading the naked catalytic cores into the scaffolds. In type II, many perfect MEMs have been used for catalyzing the model molecules, whose catalytic styles just correspond to some practical prodrug activations by natural enzymes. Therefore, these MEMs are greatly potential for practical activation. In order to improve the effectiveness and usability of the prodrug activation mediated by MEMs, some further studies are interesting and essential. First, the exploration of ...
The Diels-Alder reaction is one of the most powerful synthetic tools in organic chemistry, and asymmetric Diels-Alder catalysis allows for rapid construction of chiral carbon scaffolds. For this reason, considerable effort has been invested in developing efficient and stereoselective organo- and biocatalysts. However, Diels-Alder is a virtually unknown reaction in Nature, and to engineer an enzyme into a Diels-Alderase is therefore a challenging task. Despite several successful designs of catalytic antibodies since the 1980s, their catalytic activities have remained low, and no true artificial Diels-Alderase enzyme was reported before 2010.. In this thesis, we employ state-of-the-art computational tools to study the mechanism of organocatalyzed Diels-Alder in detail, and to redesign existing enzymes into intermolecular Diels-Alder catalysts. Papers I-IV explore the mechanistic variations when employing increasingly activated reactants and the effect of catalysis. In particular, the ...
Clinical measurements were obtained for Ramfjords six teeth (16, 21, 24, 36, 41, and 44 in the FDI two-digit notation system) in all subjects). The deepest probing depth (DPD), mean probing depth (PD), bleeding on probing (BOP), and OLeary plaque control record (PCR) were recorded. When one of the selected teeth was missing from the oral cavity, data were obtained from an adjacent tooth in the same area of the jaw. Two weeks after the first clinical measurement, all participants received full-mouth scaling and root planning, followed by professional mechanical tooth cleaning (PMTC). All procedures were performed by two trained periodontists. After that, the subjects in the test (IgY-GP) group took tablets containing anti-gingipain egg yolk antibodies (100 mg/tablet), without chewing, three times a day after a meal or brushing. Tablets stayed in the mouth for 3 to 5 minutes. Eight hours after two minutes mouth rinse with egg yolk immunoglobulin, active antibodies detected in the saliva from 18 ...
A simple receptor and substrate are used to probe the relationship between transition-state charge and the level of rate acceleration that can be created by stabilizing the transition state through hydrogen bonding. Pericyclic reactions are accelerated less than 2-fold by the receptor, whereas a conjugate addition reaction is accelerated more than 30-fold. Therefore, substrate polarization by hydrogen bonding would only appear to be effective for reactions that generate significant charge at the transition state.. ...
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TY - JOUR. T1 - Large Rate Enhancement for the Hydrolysis of a Four-membered Ring Phosphonamidate. AU - Laws, Andrew P.. AU - Stone, Julian R.. AU - Page, Michael I.. PY - 1994/5/21. Y1 - 1994/5/21. N2 - Unlike β-lactams a four-membered cyclic 1,2-azaphosphetidine shows enhanced hydrolytic reactivity compared with an acyclic analogue; the cyclic phosphonamidate 3 undergoes hydroxide-ion catalysed hydrolysis in water with endocyclic P-N fission; a corresponding acyclic derivative hydrolyses with P-O fission in basic solution, the rate difference between the cyclic and acyclic structures for P-N fission is greater than 5×108.. AB - Unlike β-lactams a four-membered cyclic 1,2-azaphosphetidine shows enhanced hydrolytic reactivity compared with an acyclic analogue; the cyclic phosphonamidate 3 undergoes hydroxide-ion catalysed hydrolysis in water with endocyclic P-N fission; a corresponding acyclic derivative hydrolyses with P-O fission in basic solution, the rate difference between the cyclic and ...
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Essays DOI: 10.1002/anie.200702210 Organocatalysis Organocatalysis Lost: Modern Chemistry, Ancient Chemistry, and an Unseen Biosynthetic Apparatus Carlos F. Barbas III* aldolases · asymmetric synthesis · biosynthesis · catalytic antibodies · organocatalysis Since the year 2000 there has been explosive growth in an area of catalytic asymmetric synthesis now known as organocatalysis, catalysis mediated solely by small organic molecules.[1] A large number of powerful asymmetric bondforming reactions and stunning cascade reactions have been reported that allow for the enantioselective synthesis of molecules with unprecedented ease. A substantial portion of this new work is founded on enamine and iminium ion based catalysis. Given the historically deep roots of this type of catalysis, why did decades pass before the basic concepts, hidden in the landmark work of Hajos and Parrish, were unveiled and exploited? I believe the answer is complex and unknowable with complete certainty, but likely ...
Shop Fructose-6-phosphate aldolase ELISA Kit, Recombinant Protein and Fructose-6-phosphate aldolase Antibody at MyBioSource. Custom ELISA Kit, Recombinant Protein and Antibody are available.
Royersford, PA, May 29, 2019. Abzyme Therapeutics LLC, a biotech company focused on developing antibodies for diagnostic and therapeutic applications, has been awarded a $299,808 Small Business Innovation Research (SBIR) Phase I Contract by the National Institute of Allergy and Infectious Diseases for implementation of strategies to improve HIV envelope protein expression and yield.. The National Institutes of Health (NIH) SBIR program is a highly competitive program for small businesses that seeks to commercialize innovative technologies with biomedical applications. This highly competitive program helps small businesses participate in federal research and development, develop life-saving technologies, and create jobs.. The promising efficacy seen in the clinical trials of HIV-1 vaccine RV144 creates a critical need for new strategies/technologies that enable development of high yielding GMP manufacturing processes for HIV antigens. Current production processes are low yielding and commercially ...
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Think of the Edwards University Summer Program as our way of setting you up for success. Youll gain insight into our culture through a combination of instructor-led courses and self-directed online learning courses. You can also get advice from recent new grad peers regarding the best way to bridge the gap between your academic life and your professional future. More importantly, the program allows you to quickly build relationships and form connections that will last for years to come through networking events with peers, mentors, and senior leaders. Youll find motivation and inspiration in a culture that emphasizes passion for our patients as you discover your own strengths.. ...
Phosphonate - Search and browse products and chemical formulations for your market. Filter products by market, construction, function, manufacturer or segment.
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TY - JOUR. T1 - Atomic dissection of the hydrogen bond network for transition-state analogue binding to purine nucleoside phosphorylase. AU - Kicska, Greg A.. AU - Tyler, Peter C.. AU - Evans, Gary B.. AU - Furneaux, Richard H.. AU - Shi, Wuxian. AU - Fedorov, Alexander. AU - Lewandowicz, Andrzej. AU - Cahill, Sean M.. AU - Almo, Steven C.. AU - Schramm, Vern L.. PY - 2002/12/10. Y1 - 2002/12/10. N2 - Immucillin-H (ImmH) and immucillin-G (ImmG) were previously reported as transition-state analogues for bovine purine nucleoside phosphorylase (PNP) and are the most powerful inhibitors reported for the enzyme (KI* = 23 and 30 pM). Sixteen new immucillins are used to probe the atomic interactions that cause tight binding for bovine PNP. Eight analogues of ImmH are identified with equilibrium dissociation constants of 1 nM or below. A novel crystal structure of bovine PNP - ImmG - PO4 is described. Crystal structures of ImmH and ImmG bound to bovine PNP indicate that nearly every H-bond donor/ ...
In this work, platinum (Pt), titanium (Ti) and silver (Ag) doped graphene oxide (GO) nanostructures were synthesized by using sonochemical technique, a relatively new technique in nanomaterial synthesis, and characterized in detail. The synthesized nanomaterials were characterized utulizing transmission electron microscopy (TEM) and X-ray photoelectron spectroscopy (XPS). TEM images and XPS spectras showed that the dopping process was successful. In addition, a multilayer graphene oxide-silver nanoparticles (M-GO-AgNPs) nano-structure was synthesized in this study for the first time, and its electrochemical performance was compared with GO-AgNPs. As a result of electrochemical studies, the rate constants of the GO-AgNPs and M-GO-AgNPs modified electrodes were found as ksanodic= 6.62 s-1 and ksanodic= 6.78 s-1, respectively. Finally, the M-GO-AgNPs nano-structure obtained by sonochemical technique, a green chemistry synthesis technique, has been found to be suitable for use as an electrochemical ...
Hotta, K.; Lange, H.; Tantillo, D. J.; Houk, K. N.; Hilvert, D.; Wilson, I. A. J. Mol. Biol. 2000, 302, 1213-1225: Catalysis of Decarboxylation by a Preorganized Heterogenous Microenvironment: Crystal Structures of Abzyme 21D8. Ujaque, G.; Tantillo, D. J.; Hu, Y.; Houk, K. N.; Hotta, K.; Hilvert, D. J. Comp. Chem. 2002, 24, 98-110: Catalysis on the Coastline: Theozyme, Molecular Dynamics, and Free Energy Perturbation Analysis of Antibody 21D8 Catalysis of the Decarboxylation of 5-Nitro-3-Carboxybenzisoxazole, part of a special issue honoring Dr. Peter A. Kollman.. Dean J. Tantillo and K. N. Houk: Analogies Between Antibody Hydrolases and Decarboxylases Poster presented at the 5th Annual Maria Goeppert-Mayer Interdisciplinary Symposium, San Diego, CA, March 4, 2000.. Dean J. Tantillo, Kinya Hotta, Donald Hilvert, and K. N. Houk: Origins of Catalysis and Cross-Reactivity for an Antibody Decarboxylase Poster presented at the 219th ACS National Meeting, San Francisco, CA, March 26-30, 2000; ...
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The SE-5175 Series Sensor/Transmitters utilize electrochemical type cells to detect the target gas. Perfect for your application.
The HORTINLEA project started in July 2013 and runs for three years with a total budget of approximately 1.5 million euros per year. Two additional ye... ...
Dive into the research topics of Recent advances in the chemistry of selenium-containing heterocycles: Six-membered ring systems. Together they form a unique fingerprint. ...
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Choi, S.-h.; Mansoorabadi, S. O.; Liu, Y.-n.; Chien, T.-C.; Liu, H.-w. Analysis of UDP-D-Apiose/UDP-D-Xylose Synthase Catalzyed Conversion of UDP-D-Apiose Phosphonate to UDP-D-Xylose Phosphonate: Implications for a Retroaldol-Aldol Mechanism. J. Am. Chem. Soc. 2012, 134, 13946-13949 ...
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Such catalytic antibodies are sometimes called "abzymes". Play media Estimates are that 90% of all commercially produced ... ISBN 1-57259-153-6. Catalytic Antibodies Simply Explained. (2010-03-06). Retrieved on 2015-11-11. Solovev, ... Catalytic heaters generate flameless heat from a supply of combustible fuel. Some of the largest-scale chemicals are produced ... Some monoclonal antibodies whose binding target is a stable molecule which resembles the transition state of a chemical ...
In 1993, his group was the first to describe how a catalytic antibody can reroute a chemically disfavored reaction to give an ... Janda's independent career started working on catalytic antibodies. ... Gao, C.; Mao, S.; Lo, C.-H. L.; Wirsching, P.; Lerner, R. A.; Janda, K. D. (May 25, 1999). "Making artificial antibodies: A ... Janda has also worked creating peptide and antibody molecules for the treatment of cancer. By employing a novel approach, he ...
"Catalytic antibodies to HIV: Physiological role and potential clinical utility". Autoimmun Rev. 7 (6): 473-9. doi:10.1016/j. ... who found a way to attach HIV-fighting antibodies to immune cells, creating a HIV-resistant cell population. ... "The challenges of eliciting neutralizing antibodies to HIV-1 and to influenza virus". Nat. Rev. Microbiol. 6 (2): 143-55. doi ...
He created the first commercially catalytic antibodies in the world. Catalytic antibody are capable of accomplishing the tasks ... These antibodies are programmed with chemical methods and specialized in treatments of chronic illnesses due to its ability to ... The main aim of founding this company is to put his research on antibodies into new therapies with the new technology. From ... He developed the first laboratory manual of antibody phage with his colleagues at TSRI. The phage display is the most straight- ...
... from catalytic monoclonal antibody), and most often called catalytic antibody, is a monoclonal antibody with catalytic activity ... So far, all catalytic antibodies produced have displayed only modest, weak catalytic activity. The reasons for low catalytic ... Planque, S; Nishiyama, Y; Taguchi, H; Salas, M; Hanson, C; Paul, S (2008). "Catalytic antibodies to HIV: Physiological role and ... Once infected by HIV, patients produce antibodies to the more changeable parts of the viral coat. The antibodies are ...
Many catalytic antibodies were developed and studied using this approach. A problem with transition state analogue selection ... The catalytic cycle is almost the same as that in nature, except the substrate is an aromatic aldehyde rather than pyruvate. ... This cyclodextrin catalytic system mimics ribonuclease A by its use of a neutral imidazole and an imidazolium cation to ... Assuming that catalytic activity largely depends on the catalyst's affinity to the transition state, one could synthesize a ...
Kuhar MJ, Carroll FI, Bharat N, Landry DW (August 2001). "Anticocaine catalytic antibodies have no affinity for RTI compounds: ...
Wagner, J; Lerner, RA; Barbas, CF (December 1995). "Efficient aldolase catalytic antibodies that use the enamine mechanism of ... Notz, Wolfgang (2000). "Catalytic Asymmetric Synthesis of anti- 1,2-Diols". Journal of the American Chemical Society. 122 (30 ... This is the same mechanism proposed by Barbas for aldolase antibodies reported by the group in 1995: This enamine mechanism ... Discovered in the 1970s the original Hajos-Parrish catalytic procedure - shown in the reaction equation, leading to the ...
The selenocysteine is arranged in an unusual Sec-His-Glu catalytic triad, which tunes its pKa. Certain species of plants are ... A reduction of 21% on TPO antibodies was reported with the dietary intake of 0.2 mg of selenium. Some microorganisms ulitize ...
... antibodies-online". McNutt, Markey C.; Lagace, Thomas A.; Horton, Jay D. (2007). "Catalytic Activity ... a peptide recognized by an antibody (GAPVPYPDPLEPR) FLAG-tag, a peptide recognized by an antibody (DYKDDDDK) HA-tag, a peptide ... a peptide recognized by an antibody (GKPIPNPLLGLDST) VSV-tag, a peptide recognized by an antibody (YTDIEMNRLGK) Xpress tag ( ... The tag is recognized by a repertoire of single-domain antibodies AviTag, a peptide allowing biotinylation by the enzyme BirA ...
November 1995). "Generation of polyclonal catalytic antibodies against cocaine using transition state analogs of cocaine ...
The catalytic site of the NA has eight functional residues ( R118, D151, R152, R224, E276, R292, R371, and Y406) surrounded by ... doi: doi:10.1056/NEJMra050740 Colman, P.M. (1994) Influenza virus neuraminidase: Structure, antibodies, and inhibitors.Protein ... There are four steps of catalytic pathways. In the first step, the binding step, the carboxylate group changes from the axial ... Influenza viruses that have reduced sensitivity to NAIs often contain mutation that affect the shape of the NA catalytic site ...
Catalytic antibodies against cocaine and methods of using and producing same Google patents US 6566084 B1 Deng, Shixian; Bharat ... octane-2-carboxamido-hexanoic acid Cocaine haptens that create catalytic anti-bodies require transitional states as affected in ... analysis of the specificity of anticocaine antibodies (Ab1) capable of inducing Ab2beta anti-idiotypic antibodies". Immunology ... "Inhibition of cocaine binding to the human dopamine transporter by a single chain anti-idiotypic antibody: its cloning, ...
"Neutralization of botulinum neurotoxin by a human monoclonal antibody specific for the catalytic light chain." PLOS One 3 (8): ... He has also worked in dilution cloning and with the antibody immunoglobulin A, among others. Levites Y, O'Nuallain B, Puligedda ... CS1 maint: discouraged parameter (link) "Salmonella Typhimurium biofilm disruption by a human antibody that binds a pan-amyloid ... Dessain SK, editor (2008). Human Antibody Therapeutics for Viral Diseases. Berlin: Springer. (Current Topics in Microbiology ...
Purification, characterization and catalytic properties". The Biochemical Journal. 271 (1): 75-86. doi:10.1042/bj2710075. PMC ... Daniele A, Di Natale P (Mar 1987). "Hunter syndrome: presence of material cross-reacting with antibodies against iduronate ...
Although their catalytic activities are only rarely strong enough to be of practical use, catalytic antibodies have provided ... One of his papers in 2013 PNAS about making more stable antibodies was retracted, due to suspect data from co-author Shiladitya ... Schultz showed that the natural molecular diversity of the immune system could be directed to generate catalytic antibodies. ... His interests are extremely wide-ranging, with applications in such diverse areas as catalytic mechanisms, cell-specialization ...
Planque S, Nishiyama Y, Taguchi H, Salas M, Hanson C, Paul S (June 2008). "Catalytic antibodies to HIV: Physiological role and ... 1990). "Infection with human immunodeficiency virus type 1 (HIV-1) among recipients of antibody-positive blood donations". Ann ... "The challenges of eliciting neutralizing antibodies to HIV-1 and to influenza virus". Nat. Rev. Microbiol. 6 (2): 143-55. doi: ...
The catalytic relevance was examined with single walled carbon nanotubes (SWCN) field effect transistors (FETs), where a ... Grivel JC, Smith-Gill SJ (1996). Lysozyme: Antigenic structure as defined by antibody and T cell responses. CRC Press. pp. 91- ... For example, blocking the catalytic activity of lysozyme by mutation of critical amino acid in the active site (52-Asp -> 52- ... The Phillips Mechanism proposed that the enzyme's catalytic power came from both steric strain on the bound substrate and ...
A number of monoclonal antibodies that bind to and inhibit PCSK9 near the catalytic domain were in clinical trials as of 2014[ ... A possible side effect of the monoclonal antibody might be irritation at the injection site. Before the infusions, participants ... A meta-analysis of 24 clinical trials has shown that monoclonal antibodies against PCSK9 can reduce cholesterol, cardiac events ... Among those inhibitors under development in December 2013 were the antibodies alirocumab, evolocumab, 1D05-IgG2 (Merck), RG- ...
Example 3. An untagged primary antibody is detected using a general secondary antibody that recognises all antibodies ... Other catalytic enzymes such as alkaline phosphatase can be used instead of peroxidases for both direct and indirect staining ... Monoclonal antibodies that consist of only one type of antibody tend to provide greater antigen specificity, and also tend to ... These stains use antibodies to bind to specific antigens, usually of protein or glycoprotein origin. Since antibodies are ...
Fragment A contains the catalytic C domain, and fragment B consists of the T and R domains: The amino-terminal catalytic domain ... It uses diphtheria toxin (truncated by the cell binding domain) coupled to an antibody to CD3ε (UCHT1). Similar to other A-B ... This unique ability can be repurposed to deliver therapeutic proteins, instead of the catalytic domain of the toxin. This toxin ...
The catalytic subunit of the complex has been identified as the product of ESA1, an essential gene required for cell cycle ... Antibodies against Esa1p specifically immunoprecipitate NuA4 activity whereas the complex purified from a temperature-sensitive ... In yeast, the complex has 13 subunits, including the catalytic subunit Esa1 (homologous to human Tip60). Post-translational ...
"Catalytic domain of PDC-E2 contains epitopes recognized by antimitochondrial antibodies in primary biliary cirrhosis". World ... These are called anti-mitochondrial antibodies (AMA) and anti-nuclear antibodies (ANA), respectively. These antibodies are ... The catalytic domains are assembled into trimers with the active site located at the subunit interface. The topology of this ... that peptides within the catalytic site may present the immunodominant epitopes recognized by the anti-PDC-E2 antibodies in PBC ...
"The covalent binding of daunomycin and adriamycin to antibodies, with retention of both drug and antibody activities". Cancer ... In 1971, Wilchek and colleagues applied this method to show that protein kinase is composed of regulatory and catalytic ... Using this method, Wilchek collaborated with a team who proved that the binding site of antibodies lies in the Fv portion of ... Early in the 1970s, they exploited Avidin as a probe and developed new methods and reagents to biotinylate antibodies and other ...
The Nck (non-catalytic region of tyrosine kinase adaptor protein 1) belongs to the adaptor family of proteins. The nck gene was ... "The SH2/SH3 domain-containing protein Nck is recognized by certain anti-phospholipase C-gamma 1 monoclonal antibodies, and its ... initially isolated from a human melanoma cDNA library using a monoclonal antibody produced against the human melanoma- ...
However, when these antibodies are immobilized (either by secondary antibody bound to plastic or by Fc receptors on other cells ... Non-catalytic tyrosine-phosphorylated receptor T-cell receptor Murphy, Kenneth (2017). Janeway's immunobiology (9th ed.). New ... Immobilized superagonistic antibodies bound to CD28 exclude CD45 phosphatases completely and the signal leading to T-cell ... Its might also be applicable to other receptors of the Non-catalytic tyrosine-phosphorylated receptors family such as CD28. On ...
Antibody-antigen interactions can also be used for serological testing, or the detection of circulating antibodies in response ... The catalytic activity of enzymes also allows lower limits of detection compared to common binding techniques. However, the ... There are limitations with using antibodies in sensors: 1. The antibody binding capacity is strongly dependent on assay ... Antibodies have a high binding constant in excess of 10^8 L/mol, which stands for a nearly irreversible association once the ...
Herceptin, a monoclonal antibody that is capable of binding to the extracellular domain of RTKs, has been used to treat HER2 ... Drugs have been developed to target the extracellular domain or the catalytic domain, thus inhibiting ligand binding, receptor ... The intracellular C terminal region displays the highest level of conservation and comprises catalytic domains responsible for ... Protein Tyrosine Phosphatase (PTPs) are a group of enzymes that possess a catalytic domain with phosphotyrosine-specific ...
Type II (AB): RIPs-II are composed of an A domain with similar catalytic activity to Type I RIPs, and a B domain with ... RIPs have been of considerable interest because of their potential use, conjugated with monoclonal antibodies, as immunotoxins ... A conserved glutamic residue has been implicated in the catalytic mechanism; this lies near a conserved arginine, which also ...
In eukaryotes, it is an obligate heterotrimer composed of a catalytic subunit A and structural subunits B and C. While the A ... "Identification and characterization of HIV-specific RNase H by monoclonal antibody". The EMBO Journal. 7 (1): 239-43. doi: ... Although two-metal-ion catalytic mechanisms are very common in enzymes involved in phosphate biochemistry, it has been a ... Tadokoro T, Kanaya S (March 2009). "Ribonuclease H: molecular diversities, substrate binding domains, and catalytic mechanism ...
Nicholas C. Price, Lewis Stevens (1999). Fundamentals of Enzymology: The Cell and Molecular Biology of Catalytic Proteins ( ... "Immunochemical evidence for six forms of rat liver cytochrome P450 obtained using antibodies against purified rat liver ...
Immunofluorescence and antibody techniques were used to localise the mutant V12rac1 protein after being microinjected into the ... Direct selection on these mutants allowed catalytic properties of B-lactamase to be identified and allowed structure-function ... the staining of the cells with antibodies showed that the increases in neurite branching was directly linked to the presence of ...
The proteasome is also involved in Intracellular antibody-mediated proteolysis of antibody-bound virions. In this ... Sakata E, Stengel F, Fukunaga K, Zhou M, Saeki Y, Förster F, Baumeister W, Tanaka K, Robinson CV (June 2011). "The catalytic ... In mammals, the β1, β2, and β5 subunits are catalytic; although they share a common mechanism, they have three distinct ... Each catalytic β subunit also possesses a conserved lysine residue required for proteolysis.[22] ...
negative regulation of catalytic activity. • positive regulation of neuron apoptotic process. • regulation of peptidyl-tyrosine ... Modulation of signal transduction pathways has been demonstrated in cross-linking with antibodies and ligand-binding (hop/STI1 ... only anti-PrPC antibodies prevented long-term memory and spatial learning deficits.[55][56] This would suggest either an ...
There are currently no therapeutic approaches targeting CASS4, and in the absence of a catalytic domain and no extracellular ... IL-5 antibodies which reduces excessive eosinophilia). This suggests CASS4 activity may be associated with immune response in ...
The catalytic efficiency (i.e., the ratio between maximal velocity and Michaelis-Menten constant) of the AEA membrane ...
GO:0048554 positive regulation of catalytic activity. • positive regulation of glycogen biosynthetic process. • positive ... Antibodies: Against TrkA: GBR-900; Against NGF: ABT-110 (PG110). *ASP-6294 ...
... an antibody that is a response to the initial exposure to an antigen, appears in the blood, viremia begins to diminish. However ... "Evasion of the innate immune response: the Old World alphavirus nsP2 protein induces rapid degradation of Rpb1, a catalytic ... Diagnosis is by either testing the blood for the virus's RNA or antibodies to the virus.[3] The symptoms can be mistaken for ... Passive immunotherapy involves administration of anti-CHIKV hyperimmune human intravenous antibodies (immunoglobulins) to those ...
... antibodies have no such constraints. An antibody's binding affinity to its target is extraordinarily high.[37] ... Gutteridge A, Thornton JM (November 2005). "Understanding nature's catalytic toolkit". Trends in Biochemical Sciences. 30 (11 ... Antibodies are protein components of an adaptive immune system whose main function is to bind antigens, or foreign substances ... Antibodies can be secreted into the extracellular environment or anchored in the membranes of specialized B cells known as ...
Favre B, Zolnierowicz S, Turowski P, Hemmings BA (Jun 1994). "The catalytic subunit of protein phosphatase 2A is carboxyl- ... detailed immunoelectron microscopic studies with rat tissues sections employing cytochrome c-specific antibodies provide ... localization of cytochrome c was shown to be specific as it was completely abolished upon adsorption of the primary antibody ...
Both GAD65 and GAD67 are regulated via phosphorylation of a dynamic catalytic loop,[10][11] but the regulation of these ... Antibodies directed against glutamic acid decarboxylase (GAD) are increasingly found in patients with other symptoms indicative ... April 2007). "GABA production by glutamic acid decarboxylase is regulated by a dynamic catalytic loop". Nature Structural & ... Stiff man human cerebellum stained with a reference anti-GAD65 monoclonal antibody. Thin arrows show presynaptic terminals ...
Antibody-drug conjugates[edit]. Antibody-drug conjugates (ADCs) comprise an antibody, drug and a linker between them. The ... The second group, catalytic inhibitors, are drugs that block the activity of topoisomerase II, and therefore prevent DNA ... Sievers EL, Linenberger M (Nov 2001). "Mylotarg: antibody-targeted chemotherapy comes of age". Current Opinion in Oncology. 13 ... They are divided into two groups: small molecule and antibodies. The massive toxicity seen with the use of cytotoxics is due to ...
1947 - Carl Ferdinand Cori and Gerty Theresa Cori, née Radnitz, United States, for their work on catalytic conversion of ... 1987 - Susumu Tonegawa, Japan, for his discovery how the genes make different antibodies[78] ... for theories about the development and control of the immune system and the discovery of monoclonal antibodies are made[75] ... for finding out the chemical structure of antibodies[63] ...
... allowing for catalytic activity, whereas in the closed conformation the two C-terminal domains are folded in on the catalytic ... Endomysial antibodies. *A collection of substrates and interaction partners of TG2 is accessible in the TRANSDAB, an ... The catalytic mechanism for crosslinking in human tTG involves the thiol group from a Cys residue in the active site of tTG.[6] ... Serology for anti-tTG antibodies has superseded older serological tests (anti-endomysium, anti-gliadin, and anti-reticulin) and ...
The A subunit is then able to use its catalytic machinery to take over the host cell's regular functions. There are four main ... along with co-administered intra-nasal delivery of virus-cholera toxin conjugate vaccine induced a virus-specific antibody ... These families are characterized by the sequence of their A subunit, as well as their catalytic ability. This family is also ...
2003). "Characterization of novel anti-cathepsin W antibodies and cellular distribution of cathepsin W in the gastrointestinal ...
Girentuximab, an antibody to carbonic anhydrase IX, is an investigational agent in clinical trials for renal cell carcinoma.[10 ... Wingo T, Tu C, Laipis PJ, Silverman DN (Nov 2001). "The catalytic properties of human carbonic anhydrase IX". Biochemical and ...
Trivalent (serotypes A, B, E) botulinum antitoxin is derived from equine sources using whole antibodies. The second antitoxin ... is heptavalent botulinum antitoxin (serotypes A, B, C, D, E, F, G), which is derived from equine antibodies which have been ...
BeiGene Announces Initiation of a Combination Trial of the BTK Inhibitor BGB-3111 with the PD-1 Antibody BGB-A317. June 2016 ...
In fact, tRNA and tRNA-like aggregates have an important catalytic influence (i. e. as ribozymes) on replication still today. ... "Production of antibodies to soluble RNA (sRNA)". Proc. Natl. Acad. Sci. USA. 54 (4): 1281-1285. Bibcode:1965PNAS...54.1281P. ...
"Quantitative analysis of extracellular-superoxide dismutase in serum and urine by ELISA with monoclonal antibody". Clinica ... positive regulation of catalytic activity. Sources:Amigo / QuickGO. Orthologs. Species. Human. Mouse. ...
The catalytic sites of cathepsin D include two critical aspartic residues (amino acid 33 and 231) located on the 14 kDa and ... Studies with domain-specific antibodies". The Journal of Biological Chemistry. 260 (8): 5105-14. PMID 3988746.. ...
Antibodies: Against TrkA: GBR-900; Against NGF: ABT-110 (PG110). *ASP-6294 ...
The molecule folds into 2 domains, an N-terminal catalytic domain, which contains the catalytic and cofactor binding sites, and ... Data for a DNA methyltransferase (DNMT) Antibody. *DNA+Modification+Methyltransferases at the US National Library of Medicine ... a larger catalytic domain containing catalytic and cofactor binding sites, and a smaller DNA recognition domain.[12] ... Both domains are required for the catalytic function of DNMT1. DNMT1 has several isoforms, the somatic DNMT1, a splice variant ...
"for their discovery of the course of the catalytic conversion of கிளைக்கோசன்"[38]. ... நோய் எதிர்ப்பாற்றல் முறைமை and the discovery of the principle for production of monoclonal antibodies"[75]. ...
The Ser-His-Asp triad has been inserted into an antibody,[48] as well as a range of other proteins.[49] Similarly, catalytic ... 2007). "Design of a serine protease-like catalytic triad on an antibody light chain displayed on the yeast cell surface". Appl ... Non-catalytic proteins have been used as scaffolds, having catalytic triads inserted into them which were then improved by ... A catalytic triad is a set of three coordinated amino acids that can be found in the active site of some enzymes.[1][2] ...
Antibodies to certain types of chromatin organization, in particular, nucleosomes, have been associated with a number of ... These nuclear bodies contain catalytic and regulatory sub-units of the proteasome and its substrates, indicating that ... Barned S, Goodman AD, Mattson DH (February 1995). "Frequency of anti-nuclear antibodies in multiple sclerosis". Neurology. 45 ( ... "The relation of immunoglobulin class, pattern of anti-nuclear antibody, and complement-fixing antibodies to DNA in sera from ...
... groups led by Tramontano and Lerner1 and by Schultz2independently demonstrated that antibodies can catalyze the hydrolysis of ... Hansen D.E. (1991) Catalytic Antibodies. In: Dordick J.S. (eds) Biocatalysts for Industry. Topics in Applied Chemistry. ... G. C. Rao, Enzyme Models Based on Boronic Acids and on a Monoclonal Antibody, Ph.D. Thesis, City University of New York (1987). ... R. Summers, Catalytic Principles of Enzyme Chemistry, Ph.D. Thesis, Harvard University (1983).Google Scholar ...
Definition of catalytic antibody. Provided by Stedmans medical dictionary and Includes medical terms and ... Definition: an antibody that has been altered to give it a catalytic activity. ...
However only a few of the antibodies generated against a given TSA turn out to be catalytic. Identifying these catalytic ... Keywords: CATALYTIC ANTIBODIES; FLUORESCENCE ASSAY; HIGH-THROUGHPUT SCREENING; TRANSITION STATE ANALOGS Document Type: Research ... Antibodies with catalytic properties can be obtained using stable transition state analogs (TSA) of chemical reactions as ... Many of the screening methods developed for assaying catalytic antibodies turn out to be generally useful for assaying ...
Monoclonal antibodies elicited to haptens that are analogs of the transition state for hydrolysis of carboxylic esters behaved ... Mechanisms are proposed to account for the different chemical behavior of these antibodies with two types of ester substrates. ... The generation of an artificial enzyme through transition state stabilization by antibodies was thus demonstrated. These ...
To our knowledge, these structures are the highest resolution catalytic antibody structures to date and provide insight into ... The x-ray crystal structures of the sulfide oxidase antibody 28B4 and of antibody 28B4 complexed with hapten have been solved ... The x-ray crystal structures of the sulfide oxidase antibody 28B4 and of antibody 28B4 complexed with hapten have been solved ... Insights into antibody catalysis: structure of an oxygenation catalyst at 1.9-angstrom resolution.. Hsieh-Wilson, L.C., Schultz ...
Catalytic domain (ab65911). Please let us know if you have used this product in your publication ... Primary antibodies. Secondary antibodies. ELISA, Matched Antibody Pairs and Multiplex Immunoassays. Cell and tissue imaging ... Get access to the best antibodies, discovery platforms, and know-how to advance your diagnostic and therapeutic programs. ...
The immune response mounted in response to the antigen chelate produces antibodies that are capable of binding both a substrate ... The present invention relates to catalytic antibodies and a method for producing the same wherein a host is immunized using an ... In general, the catalytic antibodies and method for inducing catalytic antibodies according to this invention do not rely on ... Catalytic activity is precipitated by addition of anti-mouse antibody. Antibody 6A1A6 was incubated with anti-mouse antibody ...
... which is based upon the use of designed transition-state analogues to select human catalytic antibodies capable of degrading ...
... for Anti-DPP9 antibody - Catalytic domain used in Immunocytochemistry/ Immunofluorescence. Abcam provides excellent in-house ... Primary antibodies. Secondary antibodies. ELISA and Matched Antibody Pair Kits. Cell and tissue imaging tools. Cellular and ... Non-Abcam antibody was used: Anti-rabbit IgG (H+L), F(ab')2 Fragment. Host species: Donkey. Clonality: Polyclonal. ... Custom antibody development and commercial partnerships to advance your diagnostic and therapeutic discovery. ...
Antibody 7A1 hydrolyzes cocaine to produce nonpsychoactive metabolites ecgonine methyl ester and benzoic acid. Crystal ... Complete reaction cycle of a cocaine catalytic antibody at atomic resolution Structure. 2006 Feb;14(2):205-16. doi: 10.1016/j. ... Antibody 7A1 hydrolyzes cocaine to produce nonpsychoactive metabolites ecgonine methyl ester and benzoic acid. Crystal ... of the antibody active site from "open" to "closed" to "open" for the substrate, transition state, and product states, ...
What is catalytic antibody? Meaning of catalytic antibody medical term. What does catalytic antibody mean? ... Looking for online definition of catalytic antibody in the Medical Dictionary? catalytic antibody explanation free. ... catalytic antibody. Abzyme.. cross-reacting antibody. An antibody that reacts with antigens other than its specific antigen ... Donath-Landsteiner antibody. See: Donath-Landsteiner antibody. fluorescent antibody. Abbreviation: FA. An antibody that has ...
Antibodies for proteins involved in positive regulation of catalytic activity pathways, according to their Panther/Gene ... Custom Antibody Service. Searching for an antibody we dont offer? We make custom antibodies for specific targets, species and ... Antibodies for proteins involved in positive regulation of catalytic activity pathways; according to their Panther/Gene ... If an Invitrogen™ antibody doesnt perform as described on our website or datasheet,well replace the product at no cost to you ...
Classes of biological catalysts Enzymes, RNA and antibodies Antibodies are proteins (immunoglobulins) that circulate in the ... blood and function as defense against foreign molecules Antibodies form specific stable complexes with antigens ( anti body gen ... Catalytic antibodies. Classes of biological catalysts Enzymes, RNA and antibodies Antibodies are proteins (immunoglobulins) ... PowerPoint Slideshow about Catalytic antibodies - jana. An Image/Link below is provided (as is) to download presentation ...
Human telomerase consists of three major subunits: a catalytic protein subunit called hTERT (for human TElomerase Reverse ... Primary antibody: Telomerase catalytic subunit antibody at 1:1,000 for overnight at 4°C. Secondary antibody: Peroxidase rabbit ... rabbit anti-TERT antibody, rabbit anti-Telomerase catalytic subunit antibody, hTERT, Telomerase reverse transcriptase, HEST2, ... Western Blot of Rabbit anti-Telomerase catalytic subunit antibody. Lane 1: HeLa HV. Lane 2: HeLa 6-2. Load: 10 µg per lane. ...
Catalytic elimination antibody 13G5 heavy chain. D [auth B], B [auth H]. 221. Mus musculus. Mutation(s): 0 Gene Names: Ighg, ... Catalytic elimination antibody 13G5 light chain. C [auth A], A [auth L]. 217. Mus musculus. Mutation(s): 0 ... Structure of Catalytic Elimination Antibody 13G5 from a twinned crystal in space group C2. *DOI: 10.2210/pdb2GK0/pdb ... Bifunctional Catalysis of Proton Transfer at an Antibody Active Site.. Muller, R., Debler, E.W., Steinmann, M., Seebeck, F.P., ...
... catalytic subunit Antibody. Validated: WB, ICC/IF. Tested Reactivity: Human. 100% Guaranteed. ... catalytic subunit Antibody (NBP2-16184) (0). There are no publications for DNA Polymerase delta, catalytic subunit Antibody ( ... catalytic subunit Antibody (NBP2-16184) (0) There are no reviews for DNA Polymerase delta, catalytic subunit Antibody (NBP2- ... catalytic subunit Antibody (NBP2-16184). Learn more about PTMs related to DNA Polymerase delta, catalytic subunit Antibody ( ...
The x-ray structures of three esterase-like catalytic antibodies identified by screening for catalytic activity the entire ... Structural Convergence in the Active Sites of a Family of Catalytic Antibodies ... Structural Convergence in the Active Sites of a Family of Catalytic Antibodies ... Structural Convergence in the Active Sites of a Family of Catalytic Antibodies ...
Compare Anti-platelet activating factor acetylhydrolase 1b catalytic subunit 3 Antibody Products from leading suppliers on ... antibodies-online anti-Platelet-Activating Factor Acetylhydrolase 1b, Catalytic Subunit 3 (29kDa) (PAFAH1B3) (Middle Region) ... Anti-platelet activating factor acetylhydrolase 1b catalytic subunit 3 Antibody Products. Clear ... Strong Antibody for Autophagy Receptor CALCOCO2 This antibody is good to study calcoco2 as a selective autophagy receptor. read ...
Find out information about catalytic antibody. An antibody that can cause useful chemical reactions. Catalytic antibodies are ... produced through immunization with a hapten molecule that is usually designed... Explanation of catalytic antibody ... catalytic antibody. Also found in: Dictionary, Thesaurus, Medical. Catalytic antibody. An antibody that can cause useful ... Heseds catalytic antibody technologies were developed by Dr.. Abgenix Acquires Catalytic Antibody Technology; New Class of ...
Catalytic antibodies can give insight into the mechanism of catalysis by proteins. An adventitious hydrolytic antibody that ... Catalytic antibodies have created a new dimension in protein chem. In these studies it is particularly valuable to investigate ... Catalytic antibodies: a new window on protein chemistry. Ciba Foundation Symposium, 159 (Catal.). pp. 201-210. ISSN 0300-5208 ... An antibody raised to ampicillin for anal. purposes has also been shown to catalyze hydrolysis of the β-lactam ring. ...
... a CDR grafted antibody, a single chain antibody, and a disulfide stabilized antibody each containing the monoclonal antibody. ... which is the catalytic subunit of telomerase, and provides a human chimeric antibody, ... In addition, the present invention provides a method for detecting/quantitating hTERT protein using these antibodies, and ... The present invention provides a monoclonal antibody which can specifically and efficiently recognize hTERT protein; ...
Catalytic Subunit, alpha Isozyme antibody for Immunocytochemistry (ICC). ... 84 antibody 62 antibody 14 antibody 7 antibody 9 antibody 11 antibody 6 antibody 2 antibody 4 antibody 3 antibody 5 antibody 5 ... 5 antibody 1 antibody 1 antibody 1 antibody 1 antibody ELISA. 35 antibody 31 antibody 16 antibody 1 antibody 1 antibody 2 ... 7 antibody 7 antibody 6 antibody Immunofluorescence (IF). 18 antibody 15 antibody 14 antibody 1 antibody 1 antibody 1 antibody ...
The Hapten Complexed Germline Precursor To Sulfide Oxidase Catalytic Antibody 28b4 (human). Find diseases associated with this ...
Recent trends in catalytic antibody research. / Stewart, J. D.; Benkovic, Stephen.. In: Drug News and Perspectives, Vol. 6, No ... Stewart, J. D., & Benkovic, S. (1993). Recent trends in catalytic antibody research. Drug News and Perspectives, 6(7), 522-531 ... Stewart, JD & Benkovic, S 1993, Recent trends in catalytic antibody research, Drug News and Perspectives, vol. 6, no. 7, pp. ... Recent trends in catalytic antibody research. In: Drug News and Perspectives. 1993 ; Vol. 6, No. 7. pp. 522-531. ...
A Catalytic Antibody That Accelerates the Hydrolysis of Carbonate Esters. Prediction of the Binding-Site Structure of the ... One of the antibodies, 4A1, has a relatively high activity for the substrate having a bulky group. To determine the amino acid ... Monoclonal antibodies catalyzing the hydrolysis of p-nitrophenyl alkyl carbonate were obtained using p-nitrophenyl phosphonate ...
Catalytic Subunit, alpha Isozyme antibody for Immunohistochemistry (Paraffin-embedded Sections) (IHC (p)). ... 83 antibody 61 antibody 14 antibody 7 antibody 9 antibody 11 antibody 6 antibody 7 antibody 4 antibody 3 antibody 5 antibody 5 ... 3 antibody 1 antibody 1 antibody 1 antibody 1 antibody ELISA. 34 antibody 31 antibody 16 antibody 1 antibody 1 antibody 2 ... 7 antibody 7 antibody 6 antibody Immunofluorescence (IF). 18 antibody 15 antibody 14 antibody 1 antibody 1 antibody 1 antibody ...
Find and buy Antibodies, ELISA Kits or Research Products on new online store. ... Search results for Mouse Calpain-1 catalytic subunit (CAPN1) ELISA Kit. ... 02016913804Calpain-1 catalytic subunit (CAPN1), Mouse, ELISA KitInfo Glorybioscience GBS-C0726 1 kit (96 wells plate)589.97Ask ... 02014720445Mouse Calpain-1 catalytic subunit (CAPN1) ELISA KitInfo abebio AE59176MO 1X plate of 96 wells740.10Ask ...
Remarkably efficient hydrolysis of a 4-nitrophenyl ester by a catalytic antibody raised to an ammonium hapten ... Remarkably efficient hydrolysis of a 4-nitrophenyl ester by a catalytic antibody raised to an ammonium hapten. Journal of the ... Antibodies were raised to a 1-benzazepine hapten (I) and the properties of 2 of the strongly binding clones, designated C3 and ... Neither antibody catalyzed the reaction for which they were first generated, electrophilic substitution in the benzene ring, ...
Catalytic antibodies. / Benkovic, Stephen.. In: Annual Review of Biochemistry, Vol. 61, 01.01.1992, p. 29-54.. Research output ... Catalytic antibodies. In: Annual Review of Biochemistry. 1992 ; Vol. 61. pp. 29-54. ... Benkovic, S 1992, Catalytic antibodies, Annual Review of Biochemistry, vol. 61, pp. 29-54. ... Benkovic S. Catalytic antibodies. Annual Review of Biochemistry. 1992 Jan 1;61:29-54. ...
catalytic antibody Mechanistic Analysis of the Phosphonate Transition-state Analogue-derived Catalytic and Non-catalytic ... catalytic antibody can also refer to... catalytic antibody ... catalytic antibody. in A Dictionary of Biomedicine Reference ... An antibody that will catalyse a chemical reaction, usually a monoclonal antibody directed against a transition-state analogue ... Production of a Functional Catalytic Antibody ScFv-NusA Fusion Protein in Bacterial Cytoplasm ...
  • In this chapter, we will first discuss the key developments in the study of enzymatic catalysis that led to the successful isolation of these antibody catalysts and will comment on some earlier unsuccessful attempts toward this end. (
  • Identifying these catalytic antibodies requires an efficient screening protocol for catalysis. (
  • The high resolution structures account for catalysis by transition state stabilization, and in all three antibodies a tyrosine residue participates in the oxyanion hole. (
  • Despite significant conformational differences in their combining sites, the three antibodies, which are the most efficient among those elicited, achieve catalysis in essentially the same mode, suggesting that evolution for binding to a single TSA followed by screening for catalysis lead to antibodies with structural convergence. (
  • The important feature of catalysis by antibodies is that, unlike enzymes, a desired reaction selectivity can be programmed into the antibody by using an appropriately designed hapten. (
  • Catalytic antibodies can give insight into the mechanism of catalysis by proteins. (
  • In addition, catalytic antibodies provide fundamental insight into important aspects of biological catalysis, including the importance of transition-state stabilization, proximity effects, general acid and base catalysts, electrophilic and nucleophilic catalysis, and strain. (
  • This work will provide important mechanistic information into the nature of antibody catalysis that will be relevant to the generation of more efficient catalytic antibodies, (2) to use selection schemes coupled with random mutagenesis to increase the catalytic efficiencies of existing antibodies. (
  • Catalytic antibodies have emerged as powerful tools for the chemical biologist, enabling the design and realization of specific catalysis for a wide range of chemical reactions. (
  • Catalytic antibodies are grounded upon transition state theory and envisioned as programmable mimics of enzyme catalysis. (
  • Affinity maturation of the immune response for a small-molecule hapten elicits binding site complementarity within an antibody that facilitates chemical catalysis. (
  • The range and scope of antibody catalysis is examined by reaction class, highlighting structural and mechanistic investigations to explore the roots of chemical catalysis by these designer biocatalysts. (
  • The achievements in antibody catalysis have enriched our scientific understanding of chemical catalysis, particularly by biological molecules in aqueous systems. (
  • The idea that antibodies could be designed to catalyze a specific chemical transformation was first proposed by Jencks (1) and was built on the foundations of enzyme catalysis originally conceptualized by Pauling (2). (
  • In this article, a broad overview of antibody catalysis is presented, including modern methods for eliciting catalytic antibodies, the evolution of hapten design, and advances in antibody catalysis. (
  • Catalysis is relevant to many aspects of environmental science , e.g. the catalytic converter in automobiles and the dynamics of the ozone hole . (
  • These data suggest that Glu-246 in the catalytic center must be protonated for maximum catalysis and restricts optimal activity of the enzyme to low pH. (
  • In December of 1986, groups led by Tramontano and Lerner 1 and by Schultz 2 independently demonstrated that antibodies can catalyze the hydrolysis of carboxylate esters and carbonates. (
  • In the short time since then, antibodies that catalyze a variety of additional reactions, including the sequence-specific hydrolysis of a peptide and a Claisen rearrangement, have been elicited. (
  • Monoclonal antibodies elicited to haptens that are analogs of the transition state for hydrolysis of carboxylic esters behaved as enzymic catalysts with the appropriate substrates. (
  • A Catalytic Antibody That Accelerates the Hydrolysis of Carbonate Esters. (
  • Monoclonal antibodies catalyzing the hydrolysis of p-nitrophenyl alkyl carbonate were obtained using p-nitrophenyl phosphonate as hapten. (
  • The chemical potential of the immune system was underscored when it was shown in 1986 that antibodies raised to tetrahedral, negatively-charged phosphate and phosphonate transition state analogues were capable of selectively catalyzing the hydrolysis of carbonates and esters, respectively. (
  • The Tyr34 residue of VL was substituted by His in order to introduce a catalytic imidazole into the combining site for the ester hydrolysis. (
  • The specific hydrolysis of unactivated esters bearing an R or S enantiomeric alcohol has been achieved by two separate classes of catalytic antibodies induced to bind either the R or S substrates. (
  • The antibodies exhibit rate accelerations (10(3) to 10(5] above background hydrolysis that, coupled with their antipodal specificity, provide a novel set of reagents for use in synthesis. (
  • Boucher G, Said B, Ostler EL, Resmini M, Brocklehurst K, Gallacher G. (2007) Evidence that the mechanism of antibody-catalysed hydrolysis of arylcarbamates can be determined by the structure of the immunogen used to elicit the catalytic antibody. (
  • These antibodies are an innate host defense mechanism present in the naive repertoire, and catalytic antibody-antigen binding results in hydrolysis of the target. (
  • Using a tetrahedronically designed analogue bound to a carrier molecule and injected in a mouse, Lerner, for instance, generated an antibody against the intermediate, which was also a tetrahedron and which catalyzed the hydrolysis of esters. (
  • Classes of biological catalysts Enzymes, RNA and antibodies Antibodies are proteins (immunoglobulins) that circulate in the blood and function as defense against foreign molecules Antibodies form specific stable complexes with antigens ( anti body gen erators). (
  • Search, Find and Buy Antibodies, ELISA Kits and Proteins. (
  • Antibodies are proteins that participate in the immune response by defending the body against antigens (foreign invaders). (
  • Evidence for a catalytic relationship between the HSV-1 US3 and UL34 proteins is limited but highly suggestive. (
  • The class Ia PI 3-kinases are dimers composed of a p110 catalytic subunit and a regulatory subunit with SH2 domains which can interact with IRS proteins ( 17 , 52 ). (
  • It recognizes unique aspects of pathogens - the proteins and sugars that they sport and generates antibodies to latch onto and target them for destruction. (
  • Although well established, this technology is laborious, and it is biased by the experimental animal immune system, which limits the ability to reach a high-affinity antibody against conserved mammal proteins. (
  • Additionally, the heterologous character of those proteins turn them often immunogenic to humans eliciting HAMA response (Human Anti-Mouse Antibodies), which restrict their therapeutic use [ 5 ]. (
  • The uniqueness and low cross-reactivity of the Prestige Antibodies ® to other proteins are due to a thorough selection of antigen regions, affinity purification, and stringent selection. (
  • Visit the antibody supplier page for key details, including validated applications and target specificity. (
  • J.E. Blalock, J.N. Whitaker, E.N. Benveniste, and K.L. Bost , Use of Peptides Encoded by Complimentary RNA for Generating Anti-idiotypic Antibodies of Predefined Specificity. (
  • 2. An antibody as claimed in claim 1, wherein the specificity of either the first antibody or the second antibody is directed against animal or human tumor-associated antigen. (
  • 3. An antibody as claimed in claim 1, wherein the specificity of either the first antibody or the second antibody has catalytic or enzymatic activity. (
  • Previous studies in this laboratory have determined the lack of specificity of several antibody and substrate probes of CYP2B6. (
  • The goals of the current study were to examine the expression of CYP2B6 in a bank of human liver microsome (HLM) samples using a new specific monoclonal antibody (MAb 49-10-20) and to further characterize the substrate specificity of CYP2B6. (
  • Antibodies have been used for antigen detection and therapeutics, and their specificity combined with low toxicity make them a promising pharmaceutical commodity [ 1 ]. (
  • We conclude that the substrate selectivity of MKP-1 is determined by specific protein-protein interactions coupled with catalytic activation of the phosphatase and that these interactions are restricted to members of the MAP kinase family of enzymes. (
  • However, small changes in the amino acid sequence of some enzymes can markedly alter the catalytic properties of the enzymes, affecting the substrate selectivity and subtle aspects of the catalytic mechanism. (
  • The catalytic promiscuity displayed in these enzymes may be an important factor in the natural evolution of new catalytic activities and in the development of new catalysts through protein engineering methods. (
  • These findings, taken together with the lack of catalytic activity of the anti-phosphate IgG towards the 2-nitrophenyl 4-(3-aza-2-oxoheptyl)phenyl carbonate, compel the view that the catalytic activity of the anti-phosphate IgG preparation is entirely antibody-mediated and is not due to contaminant hydrolytic enzymes. (
  • the official statement reasons: "Richard A. Lerner and Peter G. Schultz receive the Prize for demonstrating that antibodies produced by the immune system can catalyze any chemical reaction like enzymes. (
  • They combine the enormous diversity of antibodies with the catalytic properties of enzymes. (
  • Both researchers took advantage of the fact that enzymes as well as antibodies evoke structural changes in the molecules they bind to. (
  • However, the fundamental difference between the reactions of enzymes and antibodies lies in the fact that enzymes-- contrary to antibodies-- preferably stabilize high-energy activated conformations. (
  • Structural and mechanistic studies show that when the selection criteria of the immune system are changed, catalytic antibodies that have the efficiency of natural enzymes evolve, but the catalytic antibodies are much more accepting of a wide range of substrates. (
  • The resulting enzymes exhibit the necessity of these residues for catalytic function and provide evidence of their localization at the active site. (
  • The relative contributions of CYP2B6 and CYP2E1 to BUP hydroxylation were estimated by using immunoinhibitory monoclonal antibodies (MAB) to these enzymes. (
  • Then we will discuss the properties of the antibody catalysts isolated to date and will speculate on the future directions, including those involving protein engineering, that research in this area may follow. (
  • Antibodies were raised to a 1-benzazepine hapten (I) and the properties of 2 of the strongly binding clones, designated C3 and C5, as catalysts examd. (
  • Because antibodies can be generated that bind almost any molecule of interest, this new technology offers the potential to tailormake highly selective catalysts for applications in biology, chemistry and medicine. (
  • This may prove a powerful general strategy for optimizing antibody catalysts, (3) to develop general strategies for generating antibodies that selectively cleave amide bonds. (
  • however, in the case of catalytic antibodies, the reverse is the case-eliciting catalytic antibodies through biological means provides catalysts for a chemical end. (
  • These include the unexplained efficiency and diversity of mechanisms utilized by various antibody catalysts, and the observed catalytic activity of antibodies found in autoimmune serum. (
  • Catalysts may bind to the reagents to polarize bonds, e.g. acid catalysts for reactions of carbonyl compounds, or form specific intermediates that are not produced naturally, such as osmate esters in osmium tetroxide -catalyzed dihydroxylation of alkenes , or cause dissociation of reagents to reactive forms, such as chemisorbed hydrogen in catalytic hydrogenation . (
  • Human telomerase consists of three major subunits: a catalytic protein subunit called hTERT (for human TElomerase Reverse Transcriptase), a template RNA called hTR, and telomerase-associated protein (TEP-1). (
  • Like other class I catalytic subunits (p110-alpha p110-beta, and p110-delta), the encoded protein binds a p85 regulatory subunit to form PI3K. (
  • The protein encoded by this gene is one of the three catalytic subunits of protein phosphatase 1 (PP1). (
  • Optimal signaling through the PI 3-kinase pathway depends on a critical molecular balance between the regulatory and catalytic subunits. (
  • that associates with a variety of regulatory subunits.This gene encodes an alpha isoform of the catalytic subunit. (
  • It consists of a common heteromeric core enzyme, which is composed of a catalyticsubunit and a constant regulatory subunit, that associates with a variety of regulatory subunits.This gene encodes an alpha isoform of the catalytic subunit. (
  • The enzyme consists of two subunits, a heavy catalytic subunit and a light regulatory subunit. (
  • The main myosin light chain protein phosphatases (PPs) are PP1 and PP2A, which are comprised of catalytic and one or more regulatory subunits. (
  • Thereafter, we tried to identify the catalytic subunits of PPs with antibodies. (
  • The DNA-PK (Phospho-Ser2056) Polyclonal Antibody is raised in Rabbit. (
  • Resmini M., Ostler E.L., Brocklehurst K. and Gallacher G. (2004) Polyclonal catalytic antibodies. (
  • Rabbit polyclonal antibody raised against synthetic peptide of PPP2CB. (
  • Antibodies neutralize or destroy antigens in several ways. (
  • cytotoxic antibody any specific antibody directed against cellular antigens, which when bound to the antigen, activates the complement pathway or activates killer cells, resulting in cell lysis. (
  • Certain antibodies destroy antigens by immobilizing them so that the white blood cells can destroy the antigens. (
  • These antigens facilitate immune escape by interfering with antibody-mediated responses, particularly the avoidance of catalytic antibodies. (
  • Furthermore, this binding is accompanied by catalytic activation of recombinant MKP-1 protein in vitro, and these end points show an absolute correlation with MKP-1 substrate selectivity in vivo. (
  • A hybrid Fv fragment of the dinitrophenyl-binding immunoglobulin A (IgA), MPOC315, has been generated by reconstituting a recombinant variable light chain (VL) produced in Escherichia coli with a variable heavy chain (VH) derived from the antibody. (
  • This antibody is detecting both, recombinant and edogenous CesA7 (IRX3) protein. (
  • For this report, recombinant viruses were constructed to determine the significance of UL34 protein phosphorylation and US3 catalytic activity on UL34 protein localization, single-step growth, and envelopment morphology in both HEp-2 and Vero cells. (
  • In Antibody Engineering: Methods and Protocols, leading researchers and clinicians present a core collection of cutting-edge techniques for the generation, expression, optimization, and characterization of recombinant antibodies. (
  • Readily reproducible protocols for lead generation range from the cloning of human immunoglobulin genes to the generation of human recombinant antibodies by humanization approaches, molecular display technologies, and transgenic animals. (
  • To our knowledge, these structures are the highest resolution catalytic antibody structures to date and provide insight into the molecular mechanism of this antibody-catalyzed monooxygenation reaction. (
  • The immune response mounted in response to the antigen chelate produces antibodies that are capable of binding both a substrate and a metal ion, thus achieving a metal cofactor assisted reaction. (
  • Catalytic antibodies are produced through immunization with a hapten molecule that is usually designed to resemble the transition state or intermediate of a desired reaction. (
  • Making antibodies with binding pockets complementary to transition states is complicated by the fact that true transition states and most reaction intermediates are unstable. (
  • To the extent that the transition-state analog molecule resembles a true reaction transition state or intermediate, the elicited antibodies will also be complementary to that transition state or intermediate and thus lead to the catalytic acceleration of that reaction. (
  • For this reason, transition-state analog haptens can interfere with the catalytic reaction by binding in the antibody binding pocket, thereby preventing any substrate molecules from binding and reacting. (
  • This inhibition by the transition-state analog hapten is always observed with catalytic antibodies, and is used as a first level of proof that catalytic antibodies are responsible for any observed catalytic reaction. (
  • Antibodies that catalyze the Diels-Alder reaction have been characterized. (
  • An antibody that will catalyse a chemical reaction, usually a monoclonal antibody directed against a transition-state analogue, which is thereby stabilized. (
  • Antibodies that catalyze the aldol reaction, a basic carbon-carbon bond-forming reaction, have been generated. (
  • This work might lead to sequence specific peptidases for applications in biology and medicine and (4) to generate and characterize antibodies that catalyze rotation around a sigma bond, a mechanistically simple unimolecular reaction in which transition state stabilization can be easily quantitated. (
  • In this presumption, the catalytic power of an enzyme is primarily derived from the stabilization of the high energy transition state along a given reaction coordinate (Fig. 1). (
  • Therefore, a catalyst could be generated by probing the immune response for an antibody that can bind a small molecule, or hapten, that is a transition state analog of a desired chemical reaction. (
  • This antigen-specific property of the antibody is the basis of the antigen-antibody reaction that is essential to an immune response . (
  • The antigen-antibody reaction begins as soon as substances interpreted as foreign invaders gain entrance into the body. (
  • blocking antibody any antibody that by combining with an antigen blocks another immunologic reaction with the antigen. (
  • The effect of a catalyst may vary due to the presence of other substances known as inhibitors or poisons (which reduce the catalytic activity) or promoters (which increase the activity and also affect the temperature of the reaction). (
  • section describes the catalytic activity of an enzyme, i.e. a chemical reaction that the enzyme catalyzes. (
  • Antibodies, too, have a specific binding spot to bind to molecules foreign to the organism in order to mark them for immune reaction. (
  • So the hypothesis read: If an antibody could be generated that specifically recognizes and binds to a certain high-energy transition state, then this antibody could catalyze the appropriate reaction by using its binding energy. (
  • The new antibodies were specifically directed against the transition state, stabilized it and thus accelerated reaction-- in some cases considerably. (
  • The reaction carried out by this catalytic antibody was at a rate of 10(7) to 10(8) faster than without antibodies. (
  • Schultz independently generated an antibody against an artificially produced porphyrin analogue-- an antibody with properties very similar to those of the enzyme ferrochelarase, which is normally catalysed in this reaction. (
  • In 1993, his group was the first to describe how a catalytic antibody can reroute a chemically disfavored reaction to give an endo Diels-Alder cyclization product rather than the uncatalyzed exo product. (
  • Mechanisms are proposed to account for the different chemical behavior of these antibodies with two types of ester substrates. (
  • Validated in vitro and in vivo probes of CYP2B6 catalytic activity are required to relate phenotypic differences in CYP2B6 protein expression to the metabolic disposition of CYP2B6 substrates. (
  • The development of a novel method to attenuate bacterial virulence is reported, which is based upon the use of designed transition-state analogues to select human catalytic antibodies capable of degrading bacterial quorum-sensing molecules. (
  • Antibodies are also elicited in large quantity when an animal is injected with molecules, a process known as immunization. (
  • Ordinarily, only large molecules effectively elicit antibodies via immunization, so small-molecule haptens must be attached to a large protein molecule, called a carrier protein, prior to the actual immunization. (
  • However, catalytic antibodies are produced when animals are immunized with hapten molecules that are specially designed to elicit antibodies that have binding pockets capable of catalyzing chemical reactions. (
  • A brief introduction to the basic structure and function of an antibody is essential to understanding the catalytic power of a select few of these molecules. (
  • Most catalytic antibodies are IgG molecules and therefore will be the focus of this review. (
  • In particular, the selection of antibodies capable of cleaving IgE molecules. (
  • Catalytic antibodies form a new group of molecules. (
  • Antibodies, however, distinguish themselves through their ability to locate and bind molecules foreign to the organism. (
  • Using immunological methods, Lerner and Schultz generated antibodies against molecules containing phosphate and phosphonate groups. (
  • Janda has also worked creating peptide and antibody molecules for the treatment of cancer. (
  • Antibodies are the recognition arm of the immune system. (
  • The antibodies can thus recognize and bind only to the invader, identifying it as foreign and leading to its destruction by the rest of the immune system. (
  • Fortunately, the immune response of antibody and complement can be transferred passively from one individual to another, as for example the transfer of maternal antibody across the placental barrier to the fetus, who has not yet developed a mature immune system. (
  • Antibodies travel through the blood stream and are utilized by the immune system to identify and defend against bacteria, viruses, and other foreign intruders. (
  • It involves a DNA break in an immune system antibody gene and the much more rare break in a cancer-promoting gene called c-myc. (
  • The catalytic antibodies were prepared by reactive immunization, a process whereby the selection criteria of the immune system are changed from simple binding to chemical reactivity. (
  • Janda demonstrated that one could manipulate the immune system to generate antibodies against cocaine. (
  • R. Summers, Catalytic Principles of Enzyme Chemistry , Ph.D. Thesis, Harvard University (1983). (
  • At the crossroads of chemistry and immunology: catalytic antibodies. (
  • Catalytic reactions are preferred in environmentally friendly green chemistry due to the reduced amount of waste generated, [4] as opposed to stoichiometric reactions in which all reactants are consumed and more side products are formed. (
  • This affinity purified antibody was prepared from whole rabbit serum produced by repeated immunizations with a synthetic peptide corresponding to a region near the carboxy terminal end of hTERT (accession number AF018167). (
  • The present invention describes methods of screening for or selecting a catalytic antibody effective to cleave a target peptide. (
  • The presence of antibodies capable of cleaving the target peptide is identified on the basis of production of phage. (
  • The present invention relates to screening and selection methods effective for the identification of catalytic antibodies capable of cleaving a specified peptide sequence. (
  • With a few exceptions, MMPs share common structural motifs including a pro-peptide domain, a catalytic domain, a hinge region, and a hemopexin-like domain. (
  • 9. A bispecific, tetravalent antibody of FIG. 25 wherein H L represents an amino acid sequence comprising one or more hinge regions (H) and a linker peptide (L), thick lines represent peptide bonds, thin lines represent disulfide bridges connecting the two polypeptide chains of said antibody, in which the CH3 domains are replaced by human CH1 domains. (
  • Catalytic antibodies bind very tightly to the transition-state analog haptens that were used to produce them during the immunization process. (
  • The transition-state analog haptens only bind and do not react with catalytic antibodies. (
  • Haptens have been prepared to model the electrostatic or geometric attributes of a reaction's transition state and to induce combining sites having appropriate catalytic residues. (
  • Primary Antibodies are guaranteed for 1 year from date of receipt. (
  • An adventitious hydrolytic antibody that cleaves activated esters was investigated. (
  • Gul S., Sonkaria S., Pinitglang S., Florez-Álvarez J., Hussain S., Thomas E.W., Ostler E.L., Resmini M., Gallacher G. and Brocklehurst K. (2003) Improvement in hydrolytic antibody activity by change in haptenic structure from phosphate to phosphonate with retention of a common leaving group determinant: unequivocal evidence for the 'flexibility' hypothesis. (
  • In addition to demonstrating that the active site of antibody 28B4 does indeed reflect the mechanistic information programmed in the aminophosphonic acid hapten, these high-resolution structures provide a basis for enhancing turnover rates through mutagenesis and improved hapten design. (
  • Characterization of the catalytic site. (
  • M.R. Schick and R.C. Kennedy , Production and Characterization of Anti-idiotypic Antibody Reagents. (
  • C. Gramsch, R. Schulz, S. Kosin, A.H.S. Hassan, and A. Herz , Production and Characterization of Anti-idiotypic Antiopioid Receptor Antibodies. (
  • J.-Y. Couraud, S. Maillet, J. Grassi, Y. Frobert, and P. Pradelles , Characterization and Properties of Antisubstance P Anti-idiotypic Antibodies. (
  • Prestige Antibodies ® are highly characterized and extensively validated antibodies with the added benefit of all available characterization data for each target being accessible via the Human Protein Atlas portal linked just below the product name at the top of this page. (
  • an antibody that has been altered to give it a catalytic activity. (
  • 2. A monoclonal antibody of claim 1, wherein said antibody has esterolytic activity. (
  • 10. A method for producing a monoclonal antibody according to claim 9, wherein said antibody has esterolytic activity. (
  • The x-ray structures of three esterase-like catalytic antibodies identified by screening for catalytic activity the entire hybridoma repertoire, elicited in response to a phosphonate transition state analog (TSA) hapten, were analyzed. (
  • One of the antibodies, 4A1, has a relatively high activity for the substrate having a bulky group. (
  • Catalytic activity is required for binding to occur. (
  • Thus a single deliberate amino acid change can introduce significant catalytic activity into an antibody-combining site, and chemical modification data can be used to locate potential sites for the introduction of catalytic residues. (
  • RanBP2 inhibits the catalytic activity of Epac1 in vitro by binding to its catalytic CDC25 homology domain. (
  • The same mechanism can also lead to a subset of antibodies with reduced hapten affinity, but improved catalytic activity. (
  • This article attempts to assess critically the evidence for rational design of catalytic activity in antibodies. (
  • This activity is assisted by complement , which interacts with the antigen-antibody complex in such a way that the cell ruptures and there is dissolution ( lysis ) of the cell body. (
  • The antitumor activity of umbelliferone in human renal cell carcinoma via regulation of the p110γ catalytic subunit of PI3Kγ. (
  • We profoundly changed the catalytic activity and mechanism of 4-oxalocrotonate tautomerase by means of a rationally designed and synthetically produced amino acid substitution. (
  • Baranova, S , Sedykh, S & Nevinsky, GA 2021, ' New biochemical markers of HIV infection - bispecific antibodies and its catalytic activity ', FEBS Open Bio , том. (
  • J.A. Glasel , Production and Properties of Antimorphine Anti-idiotypic Antibodies and their Antiopiate Receptor Activity. (
  • a href='/help/catalytic_activity' target='_top'>More. (
  • The phosphorylation defect could be overcome by transfection of plasmids that express wild-type F10, but not by plasmids that express F10 with single amino acid substitutions that abolished catalytic activity. (
  • Nevertheless, there has been no study demonstrating that the role of F10 in assembly is dependent on its catalytic activity. (
  • Antibodies in 3 diabetic patients and 7 non-diabetic control subjects were purified using protein-G sepharose affinity column chromatography and S-300 gel filtration methods purity of the IgG antibodies was confirmed by SDS-PAGE and in western blot analysis and proteolytic activity of electrophoretically homogenous IgG antibodies was confirmed with zymogram analysis. (
  • Catalytic antibody activity elicited by active immunisation. (
  • 2. Catalytic activity was found in all 13 samples of anti-phosphate IgG but was absent in the sample of anti-sulphone IgG as well as in all samples of IgG isolated from the serum of non-immunised animals. (
  • The fact that catalytic activity was found in all 13 samples of the anti-phosphate IgG provides the first evidence that it is possible, as a routine, to elicit a catalytic antibody response in a host animal via active immunisation. (
  • Recently we reported the first known incidence of antibodies possessing catalytic sialidase activity (sialidase abzymes) in the serum of patients with multiple myeloma and systemic lupus erythematosus (SLE). (
  • The IgG antibodies were tested for sialidase activity. (
  • Data presented in this report suggest that the T. cruzi Tc24 is a B-cell superantigen based on the observations that 1) Tc24 was hydrolyzed by IgM present in serum of unexposed mice and humans and 2) exposure to Tc24 eliminated catalytic activity as early as 4 days after T. cruzi infection. (
  • SAR650984, a novel humanized CD38-targeting antibody, demonstrates potent antitumor activity in models of multiple myeloma and other CD38+ hematologic malignancies. (
  • The purpose of this study was to establish bupropion (BUP) hydroxylation as a selective in vitro marker of cytochrome P450 (CYP) 2B6 catalytic activity. (
  • These results demonstrate selectivity of BUP hydroxylation for CYP2B6 at 500 μM BUP, thereby validating its use as a diagnostic in vitro marker of CYP2B6 catalytic activity. (
  • The extent to which differential CYP2B6 protein expression reflects phenotypic differences in catalytic activity remains unknown. (
  • Therefore, alternative catalytic probes of CYP2B6 activity that maintain selectivity at substrate concentrations achieved clinically would offer greater potential for use in vivo. (
  • The SI derived unit for measuring the catalytic activity of a catalyst is the katal, which is quantified in moles per second. (
  • The productivity of a catalyst can be described by the turnover number (or TON) and the catalytic activity by the turn over frequency (TOF), which is the TON per time unit. (
  • G. C. Rao, Enzyme Models Based on Boronic Acids and on a Monoclonal Antibody , Ph.D. Thesis, City University of New York (1987). (
  • The generation of an artificial enzyme through transition state stabilization by antibodies was thus demonstrated. (
  • Catalytic antibodies have been developed by experimental approaches exploiting the analogy between antibody-antigen and enzyme-substrate interaction. (
  • Both the antibodies examined and the substrate, 7-EFC, were shown to be nonselective for this enzyme. (
  • This process yielded aldolase catalytic antibodies that approximated the rate acceleration of the natural enzyme used in glycolysis. (
  • Unlike the natural enzyme, however, the antibody aldolases catalyzed a variety of aldol reactions and decarboxylations. (
  • TERT is the catalytic component of the holoenzyme complex (TERT, DKC1, WDR79/TCAB1, NOP10, NHP2, GAR1, TEP1, EST1A, POT1 and TERC) that implicates in telomeres elongation by acting as a reverse transcriptase adding simple sequence repeats to chromosome ends by copying a template sequence within RNA component of the enzyme. (
  • Recently, antibodies, regardless of disposition or origin, have been shown to catalyze the oxidation of water, equipping the antibody with a mechanism for antigen decomposition. (
  • The Center for Disease Analysis Foundation (CDAF)* for treatment if costs are low, which can offset elimination developed a catalytic funding mechanism to allow low- and costs. (
  • Hussain S., Pinitglang S., Bailey T.S.F., Reid J.D., Noble M.A., Resmini M., Thomas E.W., Greaves R.B., Verma C.S. and Brocklehurst K. (2003) Variation in the pH-dependent pre-steady state and steady state kinetic characteristics of cysteine proteinase catalytic mechanism: evidence for electrostatic modulation of catalytic site function by the neighbouring carboxylate anion. (
  • This gene encodes a beta isoform of the catalytic subunit. (
  • CBE-labeled peptides containing the catalytic residue of lysosomal alpha-glucosidase were isolated and identified by microsequencing and amino acid analysis. (
  • The crystal structure of one of these antibodies identified the reactive lysine residue that was selected in the immunization process. (
  • The functional importance of Asp-518 and other residues around the catalytic site was studied by expression of in vitro mutagenized alpha-glucosidase cDNA in transiently transfected COS cells. (
  • The residues Trp-516 and Asp-518 are demonstrated to be critical for catalytic function. (
  • GENTAUR The Marketplace for Antibodies : Distinct binding determinants for ERK2/p38alpha and JNK map kinases mediate catalytic activation and substrate selectivity of map kinase phosphatase-1. (
  • Distinct binding determinants for ERK2/p38alpha and JNK map kinases mediate catalytic activation and substrate selectivity of map kinase phosphatase-1. (
  • An explanation for this disparity between measurement of mRNA and protein expression may be due to poor selectivity and sensitivity of antibodies used for detection of CYP2B6. (
  • The x-ray crystal structures of the sulfide oxidase antibody 28B4 and of antibody 28B4 complexed with hapten have been solved at 2.2-angstrom and 1.9-angstrom resolution, respectively. (
  • The animal produces antibodies with binding sites that are exactly complementary to some molecular feature of the invader. (
  • GCLC is the catalytic subunit of 637 amino acids with a calculated molecular weight of 72.773 kDa. (
  • Examples of such antibodies will be discussed here with emphasis on those used as probes for molecular imaging and other clinical trials. (
  • Class Ia phosphoinositide (PI) 3-kinase is a central component in growth factor signaling and is comprised of a p110 catalytic subunit and a regulatory subunit, the most common family of which is derived from the p85α gene ( Pik3r1 ). (
  • This locus encodes the catalytic subunit, while the regulatory subunit is derived from a different gene located on chromosome 1p22-p21. (
  • An antibody molecule consists of four polypeptide chains (two light and two heavy), which are joined by disulfide bonds. (
  • an immunoglobulin molecule having a specific amino acid sequence that gives each antibody the ability to adhere to and interact only with the antigen that induced its synthesis. (
  • The strategy selected for identifying the relevant catalytic domains of the molecule relies upon the production in COS-7 cells of carboxyl-terminal deletion mutants of CD38. (
  • A working dilution of 1:500 anti-TERT antibody was used followed by a 1:3,000 dilution of horseradish peroxidase- conjugated goat anti-rabbit IgG as the secondary antibody. (
  • For immunofluorescence microscopy staining, a working dilution of 1:500 was used followed by a 1:200 dilution of rhodamine-conjugated donkey anti-rabbit IgG as a secondary antibody. (
  • Immunocytochemistry/ Immunofluorescence: DNA Polymerase delta, catalytic subunit Antibody [NBP2-16184] - Immunofluorescence analysis of paraformaldehyde-fixed HeLa, using antibody at 1:200 dilution. (
  • ICC/IF Image Confocal immunofluorescence analysis (Olympus FV10i) of paraformaldehyde-fixed HeLa, using PP2A alpha, antibody (Green) at 1:500 dilution. (
  • IHC-P Image Immunohistochemical analysis of paraffin-embedded A549 xenograft, using PPP2CA , antibody at 1:100 dilution. (
  • Immunohistochemistry-Paraffin: PPP2R4 Antibody [NBP1-31266] - Paraffin-embedded A549 xenograft, using antibody at 1:100 dilution. (
  • Immunocytochemistry/Immunofluorescence: PPP2R4 Antibody [NBP1-31266] - Paraformaldehyde-fixed HeLa, using PP2A alpha antibody (Green) at 1:500 dilution. (
  • Blot was incubated in the primary antibody at a dilution of 1: 500 over night at 4°C with agitation. (
  • Western Blot: TERT Antibody [NB110-89471] - Detection of Telomerase reverse transcriptase in HeLa nuclear extracts using NB110-89471. (
  • This Telomerase reverse transcriptase antibody is useful in Immunocytochemistry/Immunofluorescence and Western blot, where a band is seen at ~120 kDa. (
  • Antibodies that can catalyze a wide variety of chemical reactions. (
  • Since that time antibodies have been generated that selectively catalyze a wide array of chemical reactions. (
  • Both being chemists and working independently of each other-- Lerner already at The Scripps Research Institute in La Jolla, Schultz at that time at the University of California at Berkeley-- they were looking for ways to use the binding energy between an antibody and its target structure to catalyze chemical reactions. (
  • Antibodies that are produced after immunization with the hapten-carrier protein conjugate are complementary to, and thus specifically bind, the hapten. (
  • The properties of the 2 antibodies are discussed with respect to their ability to bind compds. (
  • If a patient is in an emergency room with high methamphetamine levels and experiencing a cardiovascular crisis," says Vocci, "antibodies would bind the drug up and cause the individual to excrete it. (
  • Some of these new vaccines use antibodies that bind to the illegal drug, render it inactive, and then leave the bloodstream. (
  • Catalytic antibodies offer unique capabilities in a range of scenarios, including stereoselective organic synthesis, therapeutic potential in the treatment of disease, the elimination of toxins, the attenuation of agents used in chemical and biological warfare, and cessation of abused and/or addictive drugs. (
  • 17. A method for producing a monoclonal antibody according to claim 9, wherein said hapten-carrier conjugate comprises a protein carrier, a linker covalently bonded to the carrier, and a chemical moiety covalently bonded to the linker, wherein said chemical moiety has an affinity for the metal ion. (
  • This affinity purified antibody has been tested for use in immunoblotting, immunoprecipitation, and immunofluorescence microscopy. (
  • Combining-site hypermutation provides the variation in the antibody repertoire from which high-affinity clones are selected. (
  • Antibodies with catalytic properties can be obtained using stable transition state analogs (TSA) of chemical reactions as immunogens. (
  • An antibody that can cause useful chemical reactions. (
  • 5) employed this strategy, and since these seminal reports, more than 50 chemical reactions have been catalyzed by antibodies. (
  • Immunocytochemistry/ Immunofluorescence: TERT Antibody [NB110-89471] - Antibody was tested in V6.5 mouse embryonic stem cells (cat# NBP1-41162) against Dylight 488. (
  • GENTAUR The Marketplace for Antibodies : Human lysosomal alpha-glucosidase. (
  • download Catalytic within and go Human g at sheriff. (
  • When a foreign substance is introduced into the human body, the individual typically reacts by mounting an immune response by generating antibodies to this substance. (
  • With 10 recent FDA approvals of therapeutic antibody drugs and hundreds more in the biotechnology pipeline, it is clear that engineered antibodies will play a major role in treating human diseases in the 21st century. (
  • Human antibodies are of particular interest due to a lower immunogenicity response [ 1 ]. (
  • Antibody humanization bypasses this bottleneck, minimizing the HAMA response by replacing murine sequences with human framework homologous sequences [ 6 ]. (
  • The antibodies that have been generated in support of the Tissue and Cancer Atlas projects have been tested by immunohistochemistry against hundreds of normal and disease tissues and through the recent efforts of the Human Cell Atlas project, many have been characterized by immunofluorescence to map the human proteome not only at the tissue level but now at the subcellular level. (
  • Mapping of the catalytic and epitopic sites of human CD38/NAD+ glycohydrolase to a functional domain in the carboxyl terminus. (
  • N.R. Farid , Anti-idiotypic Antibodies as Probes of Hormone Receptor Structure and Function. (
  • M.B.H. Youdim, R.J. Barkey, T. Amit, and J. Guy , Anti-idiotypic Antibodies as Probes of Prolactin Receptor. (
  • Our specific aims i n this proposal are (1) to characterize the catalytic mechanisms and structures of three previously generated catalytic antibodies - a chorismate mutase, nucleoside acylase and cis-- trans enone isomerase. (
  • In contrast, bacterial chorismate mutases as e.g., chorismate mutase-prephenate dehydratase of Escherichia coli (P protein) and chorismate mutase of Salmonella typhimurium have highest catalytic activities at alkaline pH ( 4 , 5 ). (
  • Previous work had shown that AID was responsible for breaking antibody genes but not c-myc. (
  • We now know AID is causing damage in other parts of the genome, not just in antibody genes. (