Ligands: A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed)CD40 Ligand: A membrane glycoprotein and differentiation antigen expressed on the surface of T-cells that binds to CD40 ANTIGENS on B-LYMPHOCYTES and induces their proliferation. Mutation of the gene for CD40 ligand is a cause of HYPER-IGM IMMUNODEFICIENCY SYNDROME, TYPE 1.Fas Ligand Protein: A transmembrane protein belonging to the tumor necrosis factor superfamily that was originally discovered on cells of the lymphoid-myeloid lineage, including activated T-LYMPHOCYTES and NATURAL KILLER CELLS. It plays an important role in immune homeostasis and cell-mediated toxicity by binding to the FAS RECEPTOR and triggering APOPTOSIS.Protein Binding: 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.RANK Ligand: A transmembrane protein belonging to the tumor necrosis factor superfamily that specifically binds RECEPTOR ACTIVATOR OF NUCLEAR FACTOR-KAPPA B and OSTEOPROTEGERIN. It plays an important role in regulating OSTEOCLAST differentiation and activation.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Models, Molecular: Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.Molecular Sequence Data: 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.Amino Acid Sequence: 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.CD30 Ligand: A membrane-bound tumor necrosis family member found primarily on activated T-LYMPHOCYTES that binds specifically to CD30 ANTIGEN. It may play a role in INFLAMMATION and immune regulation.Membrane Glycoproteins: Glycoproteins found on the membrane or surface of cells.TNF-Related Apoptosis-Inducing Ligand: A transmembrane-protein belonging to the TNF family of intercellular signaling proteins. It is a widely expressed ligand that activates APOPTOSIS by binding to TNF-RELATED APOPTOSIS-INDUCING LIGAND RECEPTORS. The membrane-bound form of the protein can be cleaved by specific CYSTEINE ENDOPEPTIDASES to form a soluble ligand form.Signal Transduction: The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.OX40 Ligand: A membrane-bound tumor necrosis family member that is expressed on activated antigen-presenting cells such as B-LYMPHOCYTES and MACROPHAGES. It signals T-LYMPHOCYTES by binding the OX40 RECEPTOR.Protein Structure, Tertiary: The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.Protein Conformation: 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).Kinetics: The rate dynamics in chemical or physical systems.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Cells, Cultured: 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.Binding, Competitive: 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.Crystallography, X-Ray: The study of crystal structure using X-RAY DIFFRACTION techniques. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)4-1BB Ligand: A membrane bound member of the TNF superfamily that is expressed on activated B-LYMPHOCYTES; MACROPHAGES; and DENDRITIC CELLS. The ligand is specific for the 4-1BB RECEPTOR and may play a role in inducing the proliferation of activated peripheral blood T-LYMPHOCYTES.Receptors, Cell Surface: 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.Structure-Activity Relationship: The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.Membrane Proteins: 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.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Mice, Inbred C57BLMolecular Structure: The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds.Antigens, CD95: A tumor necrosis factor receptor subtype found in a variety of tissues and on activated LYMPHOCYTES. It has specificity for FAS LIGAND and plays a role in regulation of peripheral immune responses and APOPTOSIS. Multiple isoforms of the protein exist due to multiple ALTERNATIVE SPLICING. The activated receptor signals via a conserved death domain that associates with specific TNF RECEPTOR-ASSOCIATED FACTORS in the CYTOPLASM.CHO Cells: 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.Programmed Cell Death 1 Ligand 2 Protein: A costimulatory B7 antigen that has specificity for the T-CELL receptor PROGRAMMED CELL DEATH 1 RECEPTOR. It is closely-related to CD274 antigen; however, its expression is restricted to DENDRITIC CELLS and activated MACROPHAGES.Receptors, Immunologic: Cell surface molecules on cells of the immune system that specifically bind surface molecules or messenger molecules and trigger changes in the behavior of cells. Although these receptors were first identified in the immune system, many have important functions elsewhere.Transfection: 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.Receptors, TNF-Related Apoptosis-Inducing Ligand: Tumor necrosis factor receptor family members that are widely expressed and play a role in regulation of peripheral immune responses and APOPTOSIS. The receptors are specific for TNF-RELATED APOPTOSIS-INDUCING LIGAND and signal via conserved death domains that associate with specific TNF RECEPTOR-ASSOCIATED FACTORS in the CYTOPLASM.Radioligand Assay: Quantitative determination of receptor (binding) proteins in body fluids or tissue using radioactively labeled binding reagents (e.g., antibodies, intracellular receptors, plasma binders).Recombinant Fusion Proteins: 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.Peptides: 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.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.Cricetinae: A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.Apoptosis: One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Receptors, G-Protein-Coupled: The largest family of cell surface receptors involved in SIGNAL TRANSDUCTION. They share a common structure and signal through HETEROTRIMERIC G-PROTEINS.Receptors, Cytoplasmic and Nuclear: Intracellular receptors that can be found in the cytoplasm or in the nucleus. They bind to extracellular signaling molecules that migrate through or are transported across the CELL MEMBRANE. Many members of this class of receptors occur in the cytoplasm and are transported to the CELL NUCLEUS upon ligand-binding where they signal via DNA-binding and transcription regulation. Also included in this category are receptors found on INTRACELLULAR MEMBRANES that act via mechanisms similar to CELL SURFACE RECEPTORS.Mutagenesis, Site-Directed: Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.RNA, Messenger: 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.Cell Adhesion: Adherence of cells to surfaces or to other cells.Cell Line, Tumor: A cell line derived from cultured tumor cells.Mice, Knockout: Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.Antigens, CD: 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.Sequence Homology, Amino Acid: The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.Mutation: 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.Flow Cytometry: 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.Intercellular Signaling Peptides and Proteins: Regulatory proteins and peptides that are signaling molecules involved in the process of PARACRINE COMMUNICATION. They are generally considered factors that are expressed by one cell and are responded to by receptors on another nearby cell. They are distinguished from HORMONES in that their actions are local rather than distal.Receptors, sigma: A class of cell surface receptors recognized by its pharmacological profile. Sigma receptors were originally considered to be opioid receptors because they bind certain synthetic opioids. However they also interact with a variety of other psychoactive drugs, and their endogenous ligand is not known (although they can react to certain endogenous steroids). Sigma receptors are found in the immune, endocrine, and nervous systems, and in some peripheral tissues.Cell Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.Antibodies, Monoclonal: Antibodies produced by a single clone of cells.Thermodynamics: A rigorously mathematical analysis of energy relationships (heat, work, temperature, and equilibrium). It describes systems whose states are determined by thermal parameters, such as temperature, in addition to mechanical and electromagnetic parameters. (From Hawley's Condensed Chemical Dictionary, 12th ed)Oligopeptides: Peptides composed of between two and twelve amino acids.Lymphocyte Activation: 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.T-Lymphocytes: 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.Dimerization: The process by which two molecules of the same chemical composition form a condensation product or polymer.Molecular Conformation: The characteristic three-dimensional shape of a molecule.Drug Design: The molecular designing of drugs for specific purposes (such as DNA-binding, enzyme inhibition, anti-cancer efficacy, etc.) based on knowledge of molecular properties such as activity of functional groups, molecular geometry, and electronic structure, and also on information cataloged on analogous molecules. Drug design is generally computer-assisted molecular modeling and does not include pharmacokinetics, dosage analysis, or drug administration analysis.Proteins: Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.Protein Structure, Secondary: The level of protein structure in which regular hydrogen-bond interactions within contiguous stretches of polypeptide chain give rise to alpha helices, beta strands (which align to form beta sheets) or other types of coils. This is the first folding level of protein conformation.Tumor Cells, Cultured: 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.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Receptors, Notch: A family of conserved cell surface receptors that contain EPIDERMAL GROWTH FACTOR repeats in their extracellular domain and ANKYRIN repeats in their cytoplasmic domains. The cytoplasmic domain of notch receptors is released upon ligand binding and translocates to the CELL NUCLEUS where it acts as transcription factor.Models, Chemical: Theoretical representations that simulate the behavior or activity of chemical processes or phenomena; includes the use of mathematical equations, computers, and other electronic equipment.Models, Biological: Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.Gene Expression Regulation: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.COS Cells: CELL LINES derived from the CV-1 cell line by transformation with a replication origin defective mutant of SV40 VIRUS, which codes for wild type large T antigen (ANTIGENS, POLYOMAVIRUS TRANSFORMING). They are used for transfection and cloning. (The CV-1 cell line was derived from the kidney of an adult male African green monkey (CERCOPITHECUS AETHIOPS).)Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins.Receptors, Tumor Necrosis Factor: Cell surface receptors that bind TUMOR NECROSIS FACTORS and trigger changes which influence the behavior of cells.Peptide Fragments: Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.Apoptosis Regulatory Proteins: A large group of proteins that control APOPTOSIS. This family of proteins includes many ONCOGENE PROTEINS as well as a wide variety of classes of INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS such as CASPASES.Tumor Necrosis Factor Ligand Superfamily Member 13: A member of tumor necrosis factor superfamily found on MACROPHAGES; DENDRITIC CELLS and T-LYMPHOCYTES. It occurs as transmembrane protein that can be cleaved to release a secreted form that specifically binds to TRANSMEMBRANE ACTIVATOR AND CAML INTERACTOR PROTEIN; and B CELL MATURATION ANTIGEN.Magnetic Resonance Spectroscopy: Spectroscopic method of measuring the magnetic moment of elementary particles such as atomic nuclei, protons or electrons. It is employed in clinical applications such as NMR Tomography (MAGNETIC RESONANCE IMAGING).Antigens, CD40: A member of the tumor necrosis factor receptor superfamily with specificity for CD40 LIGAND. It is found on mature B-LYMPHOCYTES and some EPITHELIAL CELLS, lymphoid DENDRITIC CELLS. Evidence suggests that CD40-dependent activation of B-cells is important for generation of memory B-cells within the germinal centers. Mutations of the gene for CD40 antigen result in HYPER-IGM IMMUNODEFICIENCY SYNDROME, TYPE 3. Signaling of the receptor occurs through its association with TNF RECEPTOR-ASSOCIATED FACTORS.NK Cell Lectin-Like Receptor Subfamily K: An activating NK cell lectin-like receptor subfamily that regulates immune responses to INFECTION and NEOPLASMS. Members of this subfamily generally occur as homodimers.Endocytosis: Cellular uptake of extracellular materials within membrane-limited vacuoles or microvesicles. ENDOSOMES play a central role in endocytosis.Reverse Transcriptase Polymerase Chain Reaction: A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.Up-Regulation: A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.Allosteric Regulation: The modification of the reactivity of ENZYMES by the binding of effectors to sites (ALLOSTERIC SITES) on the enzymes other than the substrate BINDING SITES.Tumor Necrosis Factors: A family of proteins that were originally identified by their ability to cause NECROSIS of NEOPLASMS. Their necrotic effect on cells is mediated through TUMOR NECROSIS FACTOR RECEPTORS which induce APOPTOSIS.Mice, Inbred BALB CCarbon Monoxide: Carbon monoxide (CO). A poisonous colorless, odorless, tasteless gas. It combines with hemoglobin to form carboxyhemoglobin, which has no oxygen carrying capacity. The resultant oxygen deprivation causes headache, dizziness, decreased pulse and respiratory rates, unconsciousness, and death. (From Merck Index, 11th ed)Tumor Necrosis Factor-alpha: Serum glycoprotein produced by activated MACROPHAGES and other mammalian MONONUCLEAR LEUKOCYTES. It has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. Also known as TNF-alpha, it is only 30% homologous to TNF-beta (LYMPHOTOXIN), but they share TNF RECEPTORS.Dendritic Cells: Specialized cells of the hematopoietic system that have branch-like extensions. They are found throughout the lymphatic system, and in non-lymphoid tissues such as SKIN and the epithelia of the intestinal, respiratory, and reproductive tracts. They trap and process ANTIGENS, and present them to T-CELLS, thereby stimulating CELL-MEDIATED IMMUNITY. They are different from the non-hematopoietic FOLLICULAR DENDRITIC CELLS, which have a similar morphology and immune system function, but with respect to humoral immunity (ANTIBODY PRODUCTION).Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.Toll-Like Receptors: A family of pattern recognition receptors characterized by an extracellular leucine-rich domain and a cytoplasmic domain that share homology with the INTERLEUKIN 1 RECEPTOR and the DROSOPHILA toll protein. Following pathogen recognition, toll-like receptors recruit and activate a variety of SIGNAL TRANSDUCING ADAPTOR PROTEINS.Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.Cell Movement: The movement of cells from one location to another. Distinguish from CYTOKINESIS which is the process of dividing the CYTOPLASM of a cell.Coordination Complexes: Neutral or negatively charged ligands bonded to metal cations or neutral atoms. The number of ligand atoms to which the metal center is directly bonded is the metal cation's coordination number, and this number is always greater than the regular valence or oxidation number of the metal. A coordination complex can be negative, neutral, or positively charged.Blotting, Western: 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.Receptor Activator of Nuclear Factor-kappa B: A tumor necrosis factor receptor family member that is specific for RANK LIGAND and plays a role in bone homeostasis by regulating osteoclastogenesis. It is also expressed on DENDRITIC CELLS where it plays a role in regulating dendritic cell survival. Signaling by the activated receptor occurs through its association with TNF RECEPTOR-ASSOCIATED FACTORS.Organometallic Compounds: A class of compounds of the type R-M, where a C atom is joined directly to any other element except H, C, N, O, F, Cl, Br, I, or At. (Grant & Hackh's Chemical Dictionary, 5th ed)Integrins: A family of transmembrane glycoproteins (MEMBRANE GLYCOPROTEINS) consisting of noncovalent heterodimers. They interact with a wide variety of ligands including EXTRACELLULAR MATRIX PROTEINS; COMPLEMENT, and other cells, while their intracellular domains interact with the CYTOSKELETON. The integrins consist of at least three identified families: the cytoadhesin receptors(RECEPTORS, CYTOADHESIN), the leukocyte adhesion receptors (RECEPTORS, LEUKOCYTE ADHESION), and the VERY LATE ANTIGEN RECEPTORS. Each family contains a common beta-subunit (INTEGRIN BETA CHAINS) combined with one or more distinct alpha-subunits (INTEGRIN ALPHA CHAINS). These receptors participate in cell-matrix and cell-cell adhesion in many physiologically important processes, including embryological development; HEMOSTASIS; THROMBOSIS; WOUND HEALING; immune and nonimmune defense mechanisms; and oncogenic transformation.Cricetulus: A genus of the family Muridae consisting of eleven species. C. migratorius, the grey or Armenian hamster, and C. griseus, the Chinese hamster, are the two species used in biomedical research.Stereoisomerism: The phenomenon whereby compounds whose molecules have the same number and kind of atoms and the same atomic arrangement, but differ in their spatial relationships. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed)Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Cloning, Molecular: 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.Killer Cells, Natural: Bone marrow-derived lymphocytes that possess cytotoxic properties, classically directed against transformed and virus-infected cells. Unlike T CELLS; and B CELLS; NK CELLS are not antigen specific. The cytotoxicity of natural killer cells is determined by the collective signaling of an array of inhibitory and stimulatory CELL SURFACE RECEPTORS. A subset of T-LYMPHOCYTES referred to as NATURAL KILLER T CELLS shares some of the properties of this cell type.Cytokines: Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner.Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.Receptor Protein-Tyrosine Kinases: A class of cellular receptors that have an intrinsic PROTEIN-TYROSINE KINASE activity.Sequence Alignment: The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms.Surface Plasmon Resonance: 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.Solubility: The ability of a substance to be dissolved, i.e. to form a solution with another substance. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)DNA Primers: Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.Myoglobin: A conjugated protein which is the oxygen-transporting pigment of muscle. It is made up of one globin polypeptide chain and one heme group.Glycoproteins: Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins.Amino Acid Substitution: The naturally occurring or experimentally induced replacement of one or more AMINO ACIDS in a protein with another. If a functionally equivalent amino acid is substituted, the protein may retain wild-type activity. Substitution may also diminish, enhance, or eliminate protein function. Experimentally induced substitution is often used to study enzyme activities and binding site properties.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Molecular Docking Simulation: A computer simulation technique that is used to model the interaction between two molecules. Typically the docking simulation measures the interactions of a small molecule or ligand with a part of a larger molecule such as a protein.Cell Proliferation: All of the processes involved in increasing CELL NUMBER including CELL DIVISION.Receptors, Chemokine: Cell surface glycoproteins that bind to chemokines and thus mediate the migration of pro-inflammatory molecules. The receptors are members of the seven-transmembrane G protein-coupled receptor family. Like the CHEMOKINES themselves, the receptors can be divided into at least three structural branches: CR, CCR, and CXCR, according to variations in a shared cysteine motif.Histidine: An essential amino acid that is required for the production of HISTAMINE.Thiazolidinediones: THIAZOLES with two keto oxygens. Members are insulin-sensitizing agents which overcome INSULIN RESISTANCE by activation of the peroxisome proliferator activated receptor gamma (PPAR-gamma).Osteoprotegerin: A secreted member of the TNF receptor superfamily that negatively regulates osteoclastogenesis. It is a soluble decoy receptor of RANK LIGAND that inhibits both CELL DIFFERENTIATION and function of OSTEOCLASTS by inhibiting the interaction between RANK LIGAND and RECEPTOR ACTIVATOR OF NUCLEAR FACTOR-KAPPA B.L-Selectin: Cell adhesion molecule and CD antigen that serves as a homing receptor for lymphocytes to lymph node high endothelial venules.Jurkat Cells: A CELL LINE derived from human T-CELL LEUKEMIA and used to determine the mechanism of differential susceptibility to anti-cancer drugs and radiation.HEK293 Cells: A cell line generated from human embryonic kidney cells that were transformed with human adenovirus type 5.Phosphines: Inorganic or organic compounds derived from phosphine (PH3) by the replacement of H atoms. (From Grant & Hackh's Chemical Dictionary, 5th ed)Down-Regulation: A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.DNA: 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).Chemokines, CXC: Group of chemokines with paired cysteines separated by a different amino acid. CXC chemokines are chemoattractants for neutrophils but not monocytes.Cell Adhesion Molecules: Surface ligands, usually glycoproteins, that mediate cell-to-cell adhesion. Their functions include the assembly and interconnection of various vertebrate systems, as well as maintenance of tissue integration, wound healing, morphogenic movements, cellular migrations, and metastasis.Peptide Library: 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.Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.Catalysis: The facilitation of a chemical reaction by material (catalyst) that is not consumed by the reaction.Hemeproteins: Proteins that contain an iron-porphyrin, or heme, prosthetic group resembling that of hemoglobin. (From Lehninger, Principles of Biochemistry, 1982, p480)Stem Cell Factor: A hematopoietic growth factor and the ligand of the cell surface c-kit protein (PROTO-ONCOGENE PROTEINS C-KIT). It is expressed during embryogenesis and is a growth factor for a number of cell types including the MAST CELLS and the MELANOCYTES in addition to the HEMATOPOIETIC STEM CELLS.Intracellular Signaling Peptides and Proteins: Proteins and peptides that are involved in SIGNAL TRANSDUCTION within the cell. Included here are peptides and proteins that regulate the activity of TRANSCRIPTION FACTORS and cellular processes in response to signals from CELL SURFACE RECEPTORS. Intracellular signaling peptide and proteins may be part of an enzymatic signaling cascade or act through binding to and modifying the action of other signaling factors.Hydrogen-Ion Concentration: The normality of a solution with respect to HYDROGEN ions; H+. It is related to acidity measurements in most cases by pH = log 1/2[1/(H+)], where (H+) is the hydrogen ion concentration in gram equivalents per liter of solution. (McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)P-Selectin: Cell adhesion molecule and CD antigen that mediates the adhesion of neutrophils and monocytes to activated platelets and endothelial cells.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Receptor, Epidermal Growth Factor: A cell surface receptor involved in regulation of cell growth and differentiation. It is specific for EPIDERMAL GROWTH FACTOR and EGF-related peptides including TRANSFORMING GROWTH FACTOR ALPHA; AMPHIREGULIN; and HEPARIN-BINDING EGF-LIKE GROWTH FACTOR. The binding of ligand to the receptor causes activation of its intrinsic tyrosine kinase activity and rapid internalization of the receptor-ligand complex into the cell.Molecular Dynamics Simulation: A computer simulation developed to study the motion of molecules over a period of time.Amino Acid Motifs: Commonly observed structural components of proteins formed by simple combinations of adjacent secondary structures. A commonly observed structure may be composed of a CONSERVED SEQUENCE which can be represented by a CONSENSUS SEQUENCE.Electron Spin Resonance Spectroscopy: A technique applicable to the wide variety of substances which exhibit paramagnetism because of the magnetic moments of unpaired electrons. The spectra are useful for detection and identification, for determination of electron structure, for study of interactions between molecules, and for measurement of nuclear spins and moments. (From McGraw-Hill Encyclopedia of Science and Technology, 7th edition) Electron nuclear double resonance (ENDOR) spectroscopy is a variant of the technique which can give enhanced resolution. Electron spin resonance analysis can now be used in vivo, including imaging applications such as MAGNETIC RESONANCE IMAGING.DNA, Complementary: Single-stranded complementary DNA synthesized from an RNA template by the action of RNA-dependent DNA polymerase. cDNA (i.e., complementary DNA, not circular DNA, not C-DNA) is used in a variety of molecular cloning experiments as well as serving as a specific hybridization probe.Lectins, C-Type: A class of animal lectins that bind to carbohydrate in a calcium-dependent manner. They share a common carbohydrate-binding domain that is structurally distinct from other classes of lectins.Enzyme Activation: Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.PPAR gamma: A nuclear transcription factor. Heterodimerization with RETINOID X RECEPTOR ALPHA is important in regulation of GLUCOSE metabolism and CELL GROWTH PROCESSES. It is a target of THIAZOLIDINEDIONES for control of DIABETES MELLITUS.Receptors, CXCR3: CXCR receptors that are expressed on the surface of a number of cell types, including T-LYMPHOCYTES; NK CELLS; DENDRITIC CELLS; and a subset of B-LYMPHOCYTES. The receptors are activated by CHEMOKINE CXCL9; CHEMOKINE CXCL10; and CHEMOKINE CXCL11.Escherichia coli: 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.Retinoid X Receptors: A subtype of RETINOIC ACID RECEPTORS that are specific for 9-cis-retinoic acid which function as nuclear TRANSCRIPTION FACTORS that regulate multiple signaling pathways.Cysteine: A thiol-containing non-essential amino acid that is oxidized to form CYSTINE.Nuclear Magnetic Resonance, Biomolecular: NMR spectroscopy on small- to medium-size biological macromolecules. This is often used for structural investigation of proteins and nucleic acids, and often involves more than one isotope.Spectrometry, Fluorescence: Measurement of the intensity and quality of fluorescence.Cell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.Macrophages: 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.)Cattle: 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.Bacterial Proteins: Proteins found in any species of bacterium.B-Lymphocytes: 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.Toll-Like Receptor 2: A pattern recognition receptor that forms heterodimers with other TOLL-LIKE RECEPTORS. It interacts with multiple ligands including PEPTIDOGLYCAN, bacterial LIPOPROTEINS, lipoarabinomannan, and a variety of PORINS.Inducible T-Cell Co-Stimulator Ligand: A B7 antigen that binds specifically to INDUCIBLE T-CELL CO-STIMULATOR PROTEIN on T-CELLS. It provides a costimulatory signal for T-cell proliferation and cytokine secretion.Receptors, Antigen, T-Cell: Molecules on the surface of T-lymphocytes that recognize and combine with antigens. The receptors are non-covalently associated with a complex of several polypeptides collectively called CD3 antigens (ANTIGENS, CD3). Recognition of foreign antigen and the major histocompatibility complex is accomplished by a single heterodimeric antigen-receptor structure, composed of either alpha-beta (RECEPTORS, ANTIGEN, T-CELL, ALPHA-BETA) or gamma-delta (RECEPTORS, ANTIGEN, T-CELL, GAMMA-DELTA) chains.Oxidation-Reduction: A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471).Palladium: A chemical element having an atomic weight of 106.4, atomic number of 46, and the symbol Pd. It is a white, ductile metal resembling platinum, and following it in abundance and importance of applications. It is used in dentistry in the form of gold, silver, and copper alloys.Receptors, Retinoic Acid: Proteins in the nucleus or cytoplasm that specifically bind RETINOIC ACID or RETINOL and trigger changes in the behavior of cells. Retinoic acid receptors, like steroid receptors, are ligand-activated transcription regulators. Several types have been recognized.Asialoglycoproteins: Endogenous glycoproteins from which SIALIC ACID has been removed by the action of sialidases. They bind tightly to the ASIALOGLYCOPROTEIN RECEPTOR which is located on hepatocyte plasma membranes. After internalization by adsorptive ENDOCYTOSIS they are delivered to LYSOSOMES for degradation. Therefore receptor-mediated clearance of asialoglycoproteins is an important aspect of the turnover of plasma glycoproteins. They are elevated in serum of patients with HEPATIC CIRRHOSIS or HEPATITIS.Receptors, Natural Killer Cell: Receptors that are specifically found on the surface of NATURAL KILLER CELLS. They play an important role in regulating the cellular component of INNATE IMMUNITY.CD4-Positive T-Lymphocytes: A critical subpopulation of T-lymphocytes involved in the induction of most immunological functions. The HIV virus has selective tropism for the T4 cell which expresses the CD4 phenotypic marker, a receptor for HIV. In fact, the key element in the profound immunosuppression seen in HIV infection is the depletion of this subset of T-lymphocytes.Epidermal Growth Factor: A 6-kDa polypeptide growth factor initially discovered in mouse submaxillary glands. Human epidermal growth factor was originally isolated from urine based on its ability to inhibit gastric secretion and called urogastrone. Epidermal growth factor exerts a wide variety of biological effects including the promotion of proliferation and differentiation of mesenchymal and EPITHELIAL CELLS. It is synthesized as a transmembrane protein which can be cleaved to release a soluble active form.Lectins: Proteins that share the common characteristic of binding to carbohydrates. Some ANTIBODIES and carbohydrate-metabolizing proteins (ENZYMES) also bind to carbohydrates, however they are not considered lectins. PLANT LECTINS are carbohydrate-binding proteins that have been primarily identified by their hemagglutinating activity (HEMAGGLUTININS). However, a variety of lectins occur in animal species where they serve diverse array of functions through specific carbohydrate recognition.Selectins: Transmembrane proteins consisting of a lectin-like domain, an epidermal growth factor-like domain, and a variable number of domains that are homologous to complement regulatory proteins. They are important cell adhesion molecules which help LEUKOCYTES attach to VASCULAR ENDOTHELIUM.Calorimetry: The measurement of the quantity of heat involved in various processes, such as chemical reactions, changes of state, and formations of solutions, or in the determination of the heat capacities of substances. The fundamental unit of measurement is the joule or the calorie (4.184 joules). (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)Protein Multimerization: The assembly of the QUATERNARY PROTEIN STRUCTURE of multimeric proteins (MULTIPROTEIN COMPLEXES) from their composite PROTEIN SUBUNITS.E-Selectin: Cell adhesion molecule and CD antigen that mediates neutrophil, monocyte, and memory T-cell adhesion to cytokine-activated endothelial cells. E-selectin recognizes sialylated carbohydrate groups related to the Lewis X or Lewis A family.Computer Simulation: Computer-based representation of physical systems and phenomena such as chemical processes.Circular Dichroism: A change from planar to elliptic polarization when an initially plane-polarized light wave traverses an optically active medium. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)Ephrin-B1: A transmembrane domain containing ephrin that is specific for EPHB1 RECEPTOR; EPHB2 RECEPTOR and EPHB3 RECEPTOR. It is widely expressed in a variety of developing and adult tissues.Receptors, Eph Family: A large family of receptor protein-tyrosine kinases that are structurally-related. The name of this family of proteins derives from original protein Eph (now called the EPHA1 RECEPTOR), which was named after the cell line it was first discovered in: Erythropoietin-Producing human Hepatocellular carcinoma cell line. Members of this family have been implicated in regulation of cell-cell interactions involved in nervous system patterning and development.Receptors, Aryl Hydrocarbon: Cytoplasmic proteins that bind certain aryl hydrocarbons, translocate to the nucleus, and activate transcription of particular DNA segments. AH receptors are identified by their high-affinity binding to several carcinogenic or teratogenic environmental chemicals including polycyclic aromatic hydrocarbons found in cigarette smoke and smog, heterocyclic amines found in cooked foods, and halogenated hydrocarbons including dioxins and polychlorinated biphenyls. No endogenous ligand has been identified, but an unknown natural messenger with a role in cell differentiation and development is suspected.Aptamers, Nucleotide: Nucleotide sequences, generated by iterative rounds of SELEX APTAMER TECHNIQUE, that bind to a target molecule specifically and with high affinity.Allosteric Site: A site on an enzyme which upon binding of a modulator, causes the enzyme to undergo a conformational change that may alter its catalytic or binding properties.Ephrin-B2: A transmembrane domain containing ephrin that binds with high affinity to EPHB1 RECEPTOR; EPHB3 RECEPTOR; and EPHB4 RECEPTOR. Expression of ephrin-B2 occurs in a variety of adult tissues. During embryogenesis, high levels of ephrin-B2 is seen in the PROSENCEPHALON; RHOMBENCEPHALON; developing SOMITES; LIMB BUD; and bronchial arches.Protein Structure, Quaternary: The characteristic 3-dimensional shape and arrangement of multimeric proteins (aggregates of more than one polypeptide chain).ThiazolesReceptors, Opioid: Cell membrane proteins that bind opioids and trigger intracellular changes which influence the behavior of cells. The endogenous ligands for opioid receptors in mammals include three families of peptides, the enkephalins, endorphins, and dynorphins. The receptor classes include mu, delta, and kappa receptors. Sigma receptors bind several psychoactive substances, including certain opioids, but their endogenous ligands are not known.Osteoclasts: A large multinuclear cell associated with the BONE RESORPTION. An odontoclast, also called cementoclast, is cytomorphologically the same as an osteoclast and is involved in CEMENTUM resorption.Iodine Radioisotopes: Unstable isotopes of iodine that decay or disintegrate emitting radiation. I atoms with atomic weights 117-139, except I 127, are radioactive iodine isotopes.Receptor, Notch1: A notch receptor that interacts with a variety of ligands and regulates SIGNAL TRANSDUCTION PATHWAYS for multiple cellular processes. It is widely expressed during EMBRYOGENESIS and is essential for EMBRYONIC DEVELOPMENT.Chemokines, CC: Group of chemokines with adjacent cysteines that are chemoattractants for lymphocytes, monocytes, eosinophils, basophils but not neutrophils.Chromatography, Affinity: 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)Cercopithecus aethiops: A species of CERCOPITHECUS containing three subspecies: C. tantalus, C. pygerythrus, and C. sabeus. They are found in the forests and savannah of Africa. The African green monkey (C. pygerythrus) is the natural host of SIMIAN IMMUNODEFICIENCY VIRUS and is used in AIDS research.Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.Antibodies: 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).Drosophila Proteins: Proteins that originate from insect species belonging to the genus DROSOPHILA. The proteins from the most intensely studied species of Drosophila, DROSOPHILA MELANOGASTER, are the subject of much interest in the area of MORPHOGENESIS and development.Antigens, CD274: An inhibitory B7 antigen that has specificity for the T-CELL receptor PROGRAMMED CELL DEATH 1 PROTEIN. CD274 antigen provides negative signals that control and inhibit T-cell responses and is found at higher than normal levels on tumor cells, suggesting its potential role in TUMOR IMMUNE EVASION.Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.Monocytes: Large, phagocytic mononuclear leukocytes produced in the vertebrate BONE MARROW and released into the BLOOD; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles.Spectrum Analysis, Raman: Analysis of the intensity of Raman scattering of monochromatic light as a function of frequency of the scattered light.Spectrophotometry: The art or process of comparing photometrically the relative intensities of the light in different parts of the spectrum.Spectrum Analysis: The measurement of the amplitude of the components of a complex waveform throughout the frequency range of the waveform. (McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)Copper: A heavy metal trace element with the atomic symbol Cu, atomic number 29, and atomic weight 63.55.Transcription, Genetic: The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.Coculture Techniques: A technique of culturing mixed cell types in vitro to allow their synergistic or antagonistic interactions, such as on CELL DIFFERENTIATION or APOPTOSIS. Coculture can be of different types of cells, tissues, or organs from normal or disease states.

Regulation of body length and male tail ray pattern formation of Caenorhabditis elegans by a member of TGF-beta family. (1/24796)

We have identified a new member of the TGF-beta superfamily, CET-1, from Caenorhabditis elegans, which is expressed in the ventral nerve cord and other neurons. cet-1 null mutants have shortened bodies and male tail abnormal phenotype resembling sma mutants, suggesting cet-1, sma-2, sma-3 and sma-4 share a common pathway. Overexpression experiments demonstrated that cet-1 function requires wild-type sma genes. Interestingly, CET-1 appears to affect body length in a dose-dependent manner. Heterozygotes for cet-1 displayed body lengths ranging between null mutant and wild type, and overexpression of CET-1 in wild-type worms elongated body length close to lon mutants. In male sensory ray patterning, lack of cet-1 function results in ray fusions. Epistasis analysis revealed that mab-21 lies downstream and is negatively regulated by the cet-1/sma pathway in the male tail. Our results show that cet-1 controls diverse biological processes during C. elegans development probably through different target genes.  (+info)

Dominant activity of activation function 1 (AF-1) and differential stoichiometric requirements for AF-1 and -2 in the estrogen receptor alpha-beta heterodimeric complex. (2/24796)

Estrogenic responses are now known to be mediated by two forms of estrogen receptors (ER), ERalpha and ERbeta, that can function as homodimers or heterodimers. As homodimers the two have been recently shown to exhibit distinct transcriptional responses to estradiol (E2), antiestrogens, and coactivators, suggesting that the ER complexes are not functionally equivalent. However, because the three possible configurations of ER complexes all recognize the same estrogen response element, it has not been possible to evaluate the transcriptional properties of the ER heterodimer complex by transfection assays. Using ER subunits with modified DNA recognition specificity, we were able to measure the transcriptional properties of ERalpha-ERbeta heterodimers in transfected cells without interference from the two ER homodimer complexes. We first demonstrated that the individual activation function 1 (AF-1) domains act in a dominant manner within the ERalpha-ERbeta heterodimer: the mixed agonist-antagonist 4-hydroxytamoxifen acts as an agonist in a promoter- and cell context-dependent manner via the ERalpha AF-1, while activation of the complex by the mitogen-activated protein kinase (MAPK) pathway requires only the ERalpha- or ERbeta-responsive MAPK site. Using ligand-binding and AF-2-defective mutants, we further demonstrated that while the ERalpha-ERbeta heterodimer can be activated when only one E2-binding competent partner is present per dimer, two functional AF-2 domains are required for transcriptional activity. Taken together, the results of this study of a retinoid X receptor-independent heterodimer complex, the first such study, provide evidence of different stoichiometric requirements for AF-1 and -2 activity and demonstrate that AF-1 receptor-specific properties are maintained within the ERalpha-ERbeta heterodimer.  (+info)

Neu differentiation factor stimulates phosphorylation and activation of the Sp1 transcription factor. (3/24796)

Neu differentiation factors (NDFs), or neuregulins, are epidermal growth factor-like growth factors which bind to two tyrosine kinase receptors, ErbB-3 and ErbB-4. The transcription of several genes is regulated by neuregulins, including genes encoding specific subunits of the acetylcholine receptor at the neuromuscular junction. Here, we have examined the promoter of the acetylcholine receptor epsilon subunit and delineated a minimal CA-rich sequence which mediates transcriptional activation by NDF (NDF-response element [NRE]). Using gel mobility shift analysis with an NRE oligonucleotide, we detected two complexes that are induced by treatment with neuregulin and other growth factors and identified Sp1, a constitutively expressed zinc finger phosphoprotein, as a component of one of these complexes. Phosphatase treatment, two-dimensional gel electrophoresis, and an in-gel kinase assay indicated that Sp1 is phosphorylated by a 60-kDa kinase in response to NDF-induced signals. Moreover, Sp1 seems to act downstream of all members of the ErbB family and thus may funnel the signaling of the ErbB network into the nucleus.  (+info)

Ligand substitution of receptor targeted DNA complexes affects gene transfer into hepatoma cells. (4/24796)

We have targeted the serpin enzyme complex receptor for gene transfer in human hepatoma cell lines using peptides < 30 amino acids in length which contain the five amino acid recognition sequence for this receptor, coupled to poly K of average chain length 100 K, using the heterobifunctional coupling reagent sulfo-LC SPDP. The number of sulfo-LC SPDP modified poly-L-lysine residues, as well as the degree of peptide substitution was assessed by nuclear magnetic resonance spectroscopy. Conjugates were prepared in which 3.5%, 7.8% or 26% of the lysine residues contained the sulfo-LC SPDP moiety. Each of these conjugates was then coupled with ligand peptides so that one in 370, one in 1039, or one in 5882 lysines were substituted with receptor ligand. Electron microscopy and atomic force microscopy were used to assess complex structure and size. HuH7 human hepatoma cells were transfected with complexes of these conjugates with the plasmid pGL3 and luciferase expression measured 2 to 16 days after treatment. All the protein conjugates in which 26% of the K residues were modified with sulfo-LC SPDP were poor gene transfer reagents. Complexes containing less substituted poly K, averaged 17 +/- 0.5 nm in diameter and gave peak transgene expression of 3-4 x 10(6) ILU/mg which persisted (> 7 x 10(5) ILU) at 16 days. Of these, more substituted polymers condensed DNA into complexes averaging 20 +/- 0.7 nm in diameter and gave five-fold less luciferase than complexes containing less substituted conjugates. As few as eight to 11 ligands per complex are optimal for DNA delivery via the SEC receptor. The extent of substitution of receptor-mediated gene transfer complexes affects the size of the complexes, as well as the intensity and duration of transgene expression. These observations may permit tailoring of complex construction for the usage required.  (+info)

p27 is involved in N-cadherin-mediated contact inhibition of cell growth and S-phase entry. (5/24796)

In this study the direct involvement of cadherins in adhesion-mediated growth inhibition was investigated. It is shown here that overexpression of N-cadherin in CHO cells significantly suppresses their growth rate. Interaction of these cells and two additional fibroblastic lines with synthetic beads coated with N-cadherin ligands (recombinant N-cadherin ectodomain or specific antibodies) leads to growth arrest at the G1 phase of the cell cycle. The cadherin-reactive beads inhibit the entry into S phase and the reduction in the levels of cyclin-dependent kinase (cdk) inhibitors p21 and p27, following serum-stimulation of starved cells. In exponentially growing cells these beads induce G1 arrest accompanied by elevation in p27 only. We propose that cadherin-mediated signaling is involved in contact inhibition of growth by inducing cell cycle arrest at the G1 phase and elevation of p27 levels.  (+info)

Thymic selection by a single MHC/peptide ligand: autoreactive T cells are low-affinity cells. (6/24796)

In H2-M- mice, the presence of a single peptide, CLIP, bound to MHC class II molecules generates a diverse repertoire of CD4+ cells. In these mice, typical self-peptides are not bound to class II molecules, with the result that a very high proportion of H2-M- CD4+ cells are responsive to the various peptides displayed on normal MHC-compatible APC. We show here, however, that such "self" reactivity is controlled by low-affinity CD4+ cells. These cells give spectacularly high proliferative responses but are virtually unreactive in certain other assays, e.g., skin graft rejection; responses to MHC alloantigens, by contrast, are intense in all assays. Possible explanations for why thymic selection directed to a single peptide curtails self specificity without affecting alloreactivity are discussed.  (+info)

Calorimetric studies on the stability of the ribosome-inactivating protein abrin II: effects of pH and ligand binding. (7/24796)

The effects of pH and ligand binding on the stability of abrin II, a heterodimeric ribosome-inactivating protein, and its subunits have been studied using high-sensitivity differential scanning calorimetry. At pH7.2, the calorimetric scan consists of two transitions, which correspond to the B-subunit [transition temperature (Tm) 319.2K] and the A-subunit (Tm 324.6K) of abrin II, as also confirmed by studies on the isolated A-subunit. The calorimetric enthalpy of the isolated A-subunit of abrin II is similar to that of the higher-temperature transition. However, its Tm is 2.4K lower than that of the higher-temperature peak of intact abrin II. This indicates that there is some interaction between the two subunits. Abrin II displays increased stability as the pH is decreased to 4.5. Lactose increases the Tm values as well as the enthalpies of both transitions. This effect is more pronounced at pH7.2 than at pH4.5. This suggests that ligand binding stabilizes the native conformation of abrin II. Analysis of the B-subunit transition temperature as a function of lactose concentration suggests that two lactose molecules bind to one molecule of abrin II at pH7.2. The presence of two binding sites for lactose on the abrin II molecule is also indicated by isothermal titration calorimetry. Plotting DeltaHm (the molar transition enthalpy at Tm) against Tm yielded values for DeltaCp (change in excess heat capacity) of 27+/-2 kJ.mol-1.K-1 for the B-subunit and 20+/-1 kJ.mol-1.K-1 for the A-subunit. These values have been used to calculate the thermal stability of abrin II and to surmise the mechanism of its transmembrane translocation.  (+info)

The integrin alpha v beta 6 binds and activates latent TGF beta 1: a mechanism for regulating pulmonary inflammation and fibrosis. (8/24796)

Transforming growth factor beta (TGF beta) family members are secreted in inactive complexes with a latency-associated peptide (LAP), a protein derived from the N-terminal region of the TGF beta gene product. Extracellular activation of these complexes is a critical but incompletely understood step in regulation of TGF beta function in vivo. We show that TGF beta 1 LAP is a ligand for the integrin alpha v beta 6 and that alpha v beta 6-expressing cells induce spatially restricted activation of TGF beta 1. This finding explains why mice lacking this integrin develop exaggerated inflammation and, as we show, are protected from pulmonary fibrosis. These data identify a novel mechanism for locally regulating TGF beta 1 function in vivo by regulating expression of the alpha v beta 6 integrin.  (+info)

Clearly, the reliability of the relative affinity of a candidate ligand relies on the validity of Eq.(6), and requires the simultaneous satisfaction of the following prerequisites for the pair of the candidate ligand and its reference ligand. (a) The candidate ligand and its reference ligand bind to the same site(s) on the target. In practice, the binding site(s) of the candidate ligand can be judged based on its competitive binding against a reference ligand but can not be optimized. (b) The candidate ligand and its reference ligand, in both the PMFS and the concentrated extract, produce peak areas within their own linear ranges. (c) The candidate ligand and its reference ligand, in both the PMFS and the concentrated extract, produce peak areas over five times the absolute values of their own intercepts of linear response. (d) The candidate ligand and its reference ligand have binding ratios of below 10% in the competitive binding system. All the later three prerequisites should be met by ...
Ligand binding assays (LBA) is an assay, or an analytic procedure, whose procedure or method relies on the binding of ligand molecules to receptors, antibodies or other macromolecules. A detection method is used to determine the presence and extent of the ligand-receptor complexes formed, and this is usually determined electrochemically or through a fluorescence detection method. This type of analytic test can be used to test for the presence of target molecules in a sample that are known to bind to the receptor. There are numerous types of ligand binding assays, both radioactive and non-radioactive. As such, ligand binding assays are a superset of radiobinding assays, which are the conceptual inverse of radioimmunoassays (RIA). Some newer types are called "mix-and-measure" assays because they do not require separation of bound ligands. Ligand binding assays are used primarily in pharmacology for various demands. Specifically, despite the human bodys endogenous receptors, hormones, and other ...
TY - CHAP. T1 - Induction of cell adhesion and cell spreading by various cell surface ligands. AU - Grinnell, F.. PY - 1977. Y1 - 1977. UR - http://www.scopus.com/inward/record.url?scp=17344391658&partnerID=8YFLogxK. UR - http://www.scopus.com/inward/citedby.url?scp=17344391658&partnerID=8YFLogxK. M3 - Chapter. AN - SCOPUS:17344391658. VL - 6. BT - Journal of Supramolecular and Cellular Biochemistry. ER - ...
Glyconanomaterials, nanomaterials carrying multiple carbohydrate ligands, provide an excellent platform for sensitive protein recognition. Using nanomaterials as the scaffold, multivalent interactions between glycan ligands and proteins have been demonstrated. However, the quantitative analysis of the binding affinity of these glyconanomaterials has been lacking. In this Article, we report a new method to measure the binding affinity of glyconanoparticle (GNP)-protein interactions based on a fluorescent competition binding assay, which yielded the apparent dissociation constant (K-d) of GNPs with the interacting protein. Au nanoparticles conjugated with underivatized mono-, oligo-, and polysaccharides were synthesized using our recently developed photocoupling chemistry. The affinities of these GNPs with lectins were measured and were several orders of magnitude higher than the corresponding free ligands with lectins. The effect of ligand display on the binding affinity of GNPs was, furthermore, ...
PREFACE TO THE SIXTH EDITION. ABBREVIATIONS.. 1. Applications in Coordination Chemistry.. 1.1. Ammine, Amido, and Related Complexes.. 1.2. Complexes of Ethylenediamine and Related Ligands.. 1.3. Complexes of Pyridine and Related Ligands.. 1.4. Complexes of Bipyridine and Related Ligands.. 1.5. Metalloporphyrins.. 1.6. Metallochlorins, Chlorophylls, and Metallophthalocyanines.. 1.7. Nitro and Nitrito Complexes.. 1.8. Lattice Water and Aquo and Hydroxo Complexes.. 1.9. Complexes of Alkoxides, Alcohols, Ethers, Ketones, Aldehydes, Esters, and Carboxylic Acids.. 1.10. Complexes of Amino Acids, EDTA, and Related Ligands.. 1.11. Infrared Spectra of Aqueous Solutions.. 1.12. Complexes of Oxalato and Related Ligands.. 1.13. Complexes of Sulfate, Carbonate, and Related Ligands.. 1.14. Complexes of b-Diketones.. 1.15. Complexes of Urea, Sulfoxides, and Related Ligands.. 1.16. Cyano and Nitrile Complexes.. 1.17. Thiocyanato and Other Pseudohalogeno Complexes.. 1.18. Complexes of Carbon Monoxide.. 1.19. ...
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Multivalency achieves strong, yet reversible binding by the simultaneous formation of multiple weak bonds. It is a key interaction principle in biology and promising for the synthesis of high-affinity inhibitors of pathogens. We present a molecular model for the binding affinity of synthetic multivalent ligands onto multivalent receptors consisting of n receptor units arranged on a regular polygon. Ligands consist of a geometrically matching rigid polygonal core to which monovalent ligand units are attached via flexible linker polymers, closely mimicking existing experimental designs. The calculated binding affinities quantitatively agree with experimental studies for cholera toxin (n = 5) and anthrax receptor (n = 7) and allow to predict optimal core size and optimal linker length. Maximal binding affinity is achieved for a core that matches the receptor size and for linkers that have an equilibrium end-to-end distance that is slightly longer than the geometric separation between ligand core ...
This invention is directed to a ligand-receptor assay for determining the presence of at least one target ligand, capable of competing with a ligand analogue conjugate for binding sites available on a ligand receptor, said ligand analogue conjugate comprising at least one ligand analogue coupled to a colloidal gold particle, in a fluid sample suspected of containing said target ligand comprising the steps of: a. contacting said fluid sample with said ligand analogue conjugate and said ligand receptor to form a homogeneous reaction mixture, the relative amounts of said ligand analogue conjugate and said ligand receptor being selected such that in the absence of said target ligand and subsequent to substantially equilibrium binding in said reaction mixture, substantially all of said ligand analogue conjugate is bound to said ligand receptor such that no unbound ligand analogue conjugate is detected as a result of the assay method; b. detecting unbound ligand analogue conjugates in said reaction mixture by
Antagonist-bound closed state GluA2 density map quality and resolutiona,b, GluA2em antagonist-bound closed state density map with coordinates for ATD dimers, LB
The new β2 Adrenoceptor (β2AR) crystal structures provide a high-resolution snapshot of receptor interactions with two particular partial inverse agonists, (−)-carazolol and timolol. However, both...
article{8565564, abstract = {Currently, there is mounting evidence that intermolecular receptor-receptor interactions may result in altered receptor recognition, pharmacology and signaling. Heterobivalent ligands have been proven useful as molecular probes for confirming and targeting heteromeric receptors. This report describes the design and synthesis of novel heterobivalent ligands for dopamine D-2-like receptors (D-2-likeR) and the -opioid receptor (OR) and their evaluation using ligand binding and functional assays. Interestingly, we identified a potent bivalent ligand that contains a short 18-atom linker and combines good potency with high efficacy both in -arrestin2 recruitment for OR and MAPK-P for D4R. Furthermore, this compound was characterized by a biphasic competition binding curve for the D4R-OR heterodimer, indicative of a bivalent binding mode. As this compound possibly bridges the D4R-OR heterodimer, it could be used as a pharmacological tool to further investigate the ...
In case functional assays are available TriCEPS coupled ligands can also be tested to see if a similar output is achievable with a TriCEPS coupled ligand compared to a ligand that is not coupled to TriCEPS.. In addition, TriCEPS V2.0 can be utilized as Flow Cytometry (FACS) reagent for detecting binding of primary amine containing molecules to cells.. As first step, the TriCEPS v.2.0 molecule is coupled to the ligand of interest (peptide, protein, Antibody, ADC or other primary amine containing molecules) and to the positive control ligand (e.g. transferrin) and negative control ligand (e.g. glycine). This coupling reaction is tested with Dot blot to assess if the coupling worked.. Then, the TriCEPS coupled ligands are then added to the non-oxidized cells to show that the ligand binds to the unknown targets at the cell surface and TriCEPS does not interfere with the ligand receptor interaction.. Flow Cytometry tests with TriCEPS coupled ligand on oxidized cells can be further performed to test ...
Binding Affinity Prediction of Protein-Ligand complex containing Zinc [ BAPPL-Z ] server computes the binding free energy of a zinc containing metalloprotein-ligand complex using an all atom energy based empirical scoring function
Recently the first community-wide assessments of the prediction of the structures of complexes between proteins and small molecule ligands have been reported in the so-called GPCR Dock 2008 and 2010 assessments. In the current review we discuss the different steps along the protein-ligand modeling workflow by critically analyzing the modeling strategies we used to predict the structures of protein-ligand complexes we submitted to the recent GPCR Dock 2010 challenge. These representative test cases, focusing on the pharmaceutically relevant G Protein-Coupled Receptors, are used to demonstrate the strengths and challenges of the different modeling methods. Our analysis indicates that the proper performance of the sequence alignment, introduction of structural adjustments guided by experimental data, and the usage of experimental data to identify protein-ligand interactions are critical steps in the protein-ligand modeling protocol.
Background: Using the popular program AutoDock, computer-aided docking of small ligands with 6 or fewer rotatable bonds, is reasonably fast and accurate. However, docking large ligands using AutoDocks recommended standard docking protocol is less accurate and computationally slow. Results: In our earlier work, we presented a novel AutoDock-based incremental protocol (DINC) that addresses the limitations of AutoDocks standard protocol by enabling improved docking of large ligands. Instead of docking a large ligand to a target protein in one single step as done in the standard protocol, our protocol docks the large ligand in increments. In this paper, we present three detailed examples of docking using DINC and compare the docking results with those obtained using AutoDocks standard protocol. We summarize the docking results from an extended docking study that was done on 73 protein-ligand complexes comprised of large ligands. We demonstrate not only that DINC is up to 2 orders of magnitude ...
While human and mouse genetics consistently have unveiled various physiological roles of members of the pGC family, overall the mode of ligand‐dependent as well as ligand‐independent activation of these transmembrane enzymes leading to intracellular cGMP synthesis remains enigmatic. The intracellular region of pGCs consists of a juxtamembranous protein kinase-homology domain, an amphipathic α‐helical or hinge region, and the C‐terminal cyclase catalytic domain (Fig 1) (reviewed by Potter, 2011). The hinge region is involved in higher order oligomerization. Hence, although pGCs contain a single cyclase site per polypeptide chain, receptor dimerization is essential for the activation of this cGMP‐synthesizing domain (Potter, 2011). The crystal structures of the extracellular domain of GC‐A, in complex with atrial natriuretic peptide, or in absence of the ligand, suggested that hormone binding induces a rotation of the juxtamembrane domains, which is transmitted across the ...
The use of surrogates either as native orthologous proteins or as optimized chimeras, which can be readily crystallized and soaked with small molecules, has been validated by its success in other fields, particularly in guiding kinase inhibitor development (Ikuta et al., 2001; Breitenlechner et al., 2004). One should bear in mind, however, that the surrogate approach has its limitations, and local structural differences may have considerable effect on ligand binding (Davies et al., 2007). HIV-1 and PFV INs are fully orthologous, with identical canonical domain folds and stoichiometry. Fortuitously, all intasome atoms (protein, DNA, metal ions) that are in contact with the soaked INSTI molecules are invariant between HIV-1 and PFV (Hare et al., 2010a). Thus, we expect that structural differences between HIV-1 and PFV intasomes that are directly relevant to INSTI binding will be small. An unbiased test of this idea can be made by comparing the active sites in isolated catalytic core domains from ...
Recently, N,N-trans Re(O)(LN-O)2X (LN-O = monoanionic N-O chelates; X = Cl or Br prior to being replaced by solvents or alkoxides) complexes have been found to be superior to the corresponding N,N-cis isomers in the catalytic reduction of perchlorate via oxygen atom transfer. However, reported methods for Re(O)(LN-O)2X synthesis often yield only the N,N-cis complex or a mixture of trans and cis isomers. This study reports a geometry-inspired ligand design rationale that selectively yields N,N-trans Re(O)(LN-O)2Cl complexes. Analysis of the crystal structures revealed that the dihedral angles (DAs) between the two LN-O ligands of N,N-cis Re(O)(LN-O)2Cl complexes are less than 90°, whereas the DAs in most N,N-trans complexes are greater than 90°. Variably sized alkyl groups (−Me, −CH2Ph, and −CH2Cy) were then introduced to the 2-(2′-hydroxyphenyl)-2-oxazoline (Hhoz) ligand to increase steric hindrance in the N,N-cis structure, and it was found that substituents as small as −Me ...
In the case of the CaM-CaMKK complex, we obtained a set of desired near-native decoys with lowest interaction energy (Figure 3) and high Tc-IFPs (Figure 4). These results are explained by the structure of the CaM-CaMKK complex, which is different from those of the CaM-CNG and CaM-PMCA complexes. The globular cognate structure of CaM in the CaM-CaMKK complex differed only slightly from that of the CaM-CNG complex, indicating that the cavity of the CaM-CaMKK complex is narrower than that of the CaM-CNG complex, as shown in Figure 2. In contrast to the simple alpha helical structure of the CNG and PMCA ligand peptides, the CaMKK ligand peptide has an additional loop region in the C-terminal end. These structural features of the ligand have contributed in obtaining a set of near-native decoys for the CaM-CaMKK complex. In context with the shape of the ligand peptide, it is noteworthy that we found CaM-CNG b-decoys in which the CNG was bound to the CaM cavity in an inverse manner as compared to the ...
A soluble factor produced by HTU-34 cells is responsible for αvβ3 ligand-binding activity and recruitment to FCs. (A) Adhesion assay. Treatment of HTU-34 cel
Hi, When you say wrong postion, what does it mean? are the 2 ligands you are trying to refine being pushed away from each other? If that is the case first thing I would check is the ALTLOC comlumn of their pdb file entries. Make sure one is ALTLOC A and the other ALTLOC B. I have refined with ligands in four different positions before using phenix before and got satisfactory results... Hope this helps, -- Yuri Pompeu ...
The fact that over 30% of current pharmaceuticals target heptahelical G protein-coupled receptors (GPCRs) attests to their tractability as drug targets. While GPCR drug development has traditionally focused on conventional agonists and antagonists, the growing appreciation that GPCRs mediate physiologically relevant effects via both G protein and non-G protein effectors has prompted the search for ligands that can bias downstream signaling in favor of one or the other process. Biased ligands are novel entities with distinct signaling profiles dictated by ligand structure, and the potential prospect of biased ligands as better drugs has been pleonastically proclaimed. Indeed, preclinical proof-of-concept studies have demonstrated that both G protein and arrestin pathway-selective ligands can promote beneficial effects in vivo while simultaneously antagonizing deleterious ones. But along with opportunity comes added complexity and new challenges for drug discovery. If ligands can be biased, then ...
Carroll, F., Blough, B., Mascarella, S., Xu, H., Goodman, C. B., & Rothman, R. B. (1993). Synthesis and Ligand Binding at PCP Sites 1 and 2 for Hexahydro-2-substituted-1-methylindeno[1,2-b]pyrroles. Medicinal Chemistry Research, 3, 178 ...
The Rho GTPases are known regulators of the actin cytoskeleton and affect multiple cellular activities including cell morphology, polarity, migration, proliferation and apoptosis, phagocytosis, cytokinesis, adhesion, vesicular transport, transcription, and neurite extension and retraction. Like DOCK2, DOCK8 is likely to regulate the activity of GTPases and thus be involved in cytoskeletal changes associated with various cellular processes. DOCK8 is proposed to serve as an effector downstream of CD19 and PI3K to promote G protein signaling events critical for integrin polarization at the synapse and for the survival of marginal zone B cells and germinal center (GC) B cells. During a T cell-dependent humoral immune response, CD4+ T helper cell subsets including TFH, Th1 and Th2 cells migrate to the T cell/B cell borders in secondary lymphoid organs, and interact with cognate antigen-specific B cells through the pairing of T cell and B cell surface ligands and receptors such as CD40 with its ligand ...
Low-affinity ligands can be efficiently optimized into high-affinity drug leads by structure based drug design when atomic-resolution structural information on the protein/ligand complexes is availabl
The problem with method #1 is that it is very labor intensive, and that any compound proposed may be difficult and/or expensive to acquire. The problem with approach #2 is that the compounds may still be difficult to acquire, although there are strategies to overcome this limitation. It can also be, relatively speaking, slow. The third approach, docking, is the one taken by DOCK and its graphical user interface, DOCK Blaster. It is particularly pragmatic when used to screen a database of compounds that can be acquired rapidly, such as those in ZINC, because the time from hypothesis to experimental test can be very short, and the project can progress rapidly. ...
Ligand binding affinities at G-protein coupled receptors (GPCRs) have historically been determined using a radioligand that competes for receptor binding sites against an unlabeled drug-like compound. But the potential hazards of open-source radioisotope handling, and the environmental impact of radioisotope disposal, make this a less desirable and costly technology. Therefore, new fluorescent based alternatives have been developed to replace radioligands.
Photoaffinity cross‐linking is a rapidly developing technology for studying biomolecular interactions, including protein ligand‐receptor binding
One of the major challenges in the field of system biology is to understand the interaction between a wide range of proteins and ligands. In the past, methods have been developed for predicting binding sites in a protein for a limited number of ligands.. ...
A method is disclosed for coupling a ligand within a porous support. The method involves mixing ligand and porous support under conditions sufficient to suppress coupling conditions of the ligand to the porous support while enhancing the relative rate of diffusion, to the rate of reaction, of the ligand into and within the porous support, and then altering the conditions to enhance rapid coupling of the ligand within the porous support. The alteration from diffusion conditions to coupling conditions involves a change in the reaction solution of pH, ionic strength, temperature, coupling competitor, such that a relatively lower Thiele Modulus during diffusion conditions changes to a relatively higher Thiele Modulus during coupling conditions. Derivatized porous supports produced according to the method are also disclosed. The derivatized porous support has enhanced functional efficiency. Derivatized porous supports prepared from azlactone-functional porous supports are also disclosed ...
Users can interactively analyze protein-small ligand binding modes with statistically determined interaction patterns rather than relying on a priori knowledge of the users.
Bishwa I am using Phenix 1.0-1069 for refinement and coot 0.7-pre-1 for , visualization , and rebuilding. I used SMILES in coot to build the ligand and then merged , them , with PDB.I had to do this as a separate step for both chains and the .cif , file , so produced was not accepted for refinement. , Why? Can you send me the files directly? , , I used readyset to obtain the restrains for refinement using .pdb file, , even , though my refinement works, when i try to run real build refine in coot I , get , this error message: , It would be better to generate the restraints using the SMILES in eLBOW and then pass the restraints file to ReadySet!. Send me the file and we can fix them Nigel NB. Any files sent to me will be held in strictest confidence. , , Failed to match (to the dictionary) the following model atom names: , HB3 , "O6" "C10" "C11" "C12" "O7" "C13" "O5" "C8" "C9" ...... , That would cause exploding atoms, so the refinement didnt start. , , Could someone help me with fixing this ...
Reactome is pathway database which provides intuitive bioinformatics tools for the visualisation, interpretation and analysis of pathway knowledge.
Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Cell and Molecular Biology. ...
The interaction between cells and extracellular matrix HA is clearly of fundamental importance both during embryonic limb development and in processes such as wound healing and inflammation in later adult life (19-22). Such importance predicts that many receptors must be involved in HA adhesion, and that complex mechanisms must exist to regulate both their expression and their ligand-binding affinity. Yet at present, the list of professional cell surface HA receptors is small and includes only the CD44 molecule, RHAMM, and the LEC HA receptors. Furthermore, deletion of the gene for CD44, the most abundant and widely expressed of these, has little if any deleterious effects on the embryo (43). Thus, it has become increasingly clear to many workers in the field that additional receptors for HA are likely to exist within the genome.. In this paper we have described the primary structure and biological function of one such receptor, termed LYVE-1, which is present within vessels of the lymphatic ...
We developed models for physically realistic consecutive and independent binding schemes and compared them with the Hill equation (Figure 1). It follows from this comparison that the "half-effect" concentration may significantly differ from the conventional Hill equation depending on the binding mechanism. We used our models to rigorously investigate mechanisms for second messenger activation by multisite proteins. We show that differential and selective activation of different targets by the same protein-ligand complex (Ca2+ and calmodulin, for example) can be achieved by biologically active non-saturated intermediate multisite protein-ligand complexes. ...
For downstream processes that utilize a Praesto® Jetted A50 capture step, Repligen offers the only kit on the market that includes the NGL-Impact™ A Ligand standard for the most accurate quantitation. Exact matched Protein A reference standard (NGL-Impact™ A Ligand) Sensitivity of 0.1 ng/mL Recovery: 80-120% Accuracy &
Binding Affinity Prediction of Protein-Ligand complex containing Zinc [ BAPPL-Z ] server computes the binding free energy of a zinc containing metalloprotein-ligand complex using an all atom energy based empirical scoring function
As for primary fragment screening, I encourage a project teams to use bio-assay when possible. Certainly not all assays are able to reliably detect weak ligands and many suffer from background interference of colored or fluorescent compounds at high concentration. In some cases the use of a "kinetic read" helps with this. I then advocate follow-up with a biophysical assay such as NMR-STD, biacore, or ITD-calorimetry. In cases where the bioassay is not reliable and protein is abundantly available, you can reverse the order to put the biophysical assay first. In both cases, keep the X-ray step toward the end when there is a short list of validated hits with high ligand efficency, and solubility about 10-times above Kd. ...
2M0P: Gentamicin binds to the megalin receptor as a competitive inhibitor using the common ligand binding motif of complement type repeats: insight from the nmr structure of the 10th complement type repeat domain alone and in complex with gentamicin.
In downstream purification of monoclonal antibodies (MAbs), the single greatest contributor to manufacturing costs is the expensive capture step typically based on protein A affinity chromatography. Almost since its introduction to bioprocessing, efforts have been made to reduce the cost of this step. Several alternative ligands have been promulgated as potential replacements for protein A, but they have proven difficult to adopt and scale up. Supplier companies have pushed for increases in capacity and economics, but those are always accompanied…. ...
DI-fusion, le Dépôt institutionnel numérique de lULB, est loutil de référencementde la production scientifique de lULB.Linterface de recherche DI-fusion permet de consulter les publications des chercheurs de lULB et les thèses qui y ont été défendues.
Hamster Monoklonal CD40 Ligand Antikörper für BP, FACS, Neut. Jetzt diesen anti-CD40 Ligand Antikörper bestellen. | Produkt ABIN4260972
most probably you have not selected the first ligand in the first step of the protein setup in the Heteroatoms box in the second docking. You must select the ligand if you want it to keep it during the docking. If it is not the problem, please share the url of the docking in question ...
NOTE: The prediction model might be improved by removing some chemicals from the superposition in Step 1. It might be a subjective call as to which chemicals are good for the model and which ones should be removed. In some cases a crystal structure of a protein-ligand complex is available and the ligand pose would be a good template to superimpose onto ...
2ZQ1: Congeneric but still distinct: how closely related trypsin ligands exhibit different thermodynamic and structural properties
Here we report on the structure-based optimization of antibody-recruiting molecules targeting HIV gp120 (ARM-H). These studies have leveraged a combination of medicinal chemistry, biochemical and cellular assay analysis, and computation. Our findings have afforded an optimized analog of ARM-H, which is ∼1000
A new series of platinacyclopentanes (2a-2f) and platinacycloheptanes (3a-3f) of the type [Pt(N^P)(CH2)n] (n = 4, 6) were obtained by the reaction of [Pt(COD)(CH2)n] with the appropriate iminophosphine ligand (1a-1f). These complexes were characterised using a variety of spectroscopic and analytical techniqu
Gentaur molecular products has all kinds of products like :search , Reliatech \ Anti_Mouse, mab Flt_3 Ligand Source Rat \ 103-M383 for more molecular products just contact us
Cool! By the way - The experimental names result of generating the name based on the 3d-prepared ligand, yes? Why not use the unprepared 2d-model, then the name would be correct and not interfered with the PM6 calculations ...
reference: Conformation of a peptide ligand bound to its G-protein coupled receptor., Inooka H, Ohtaki T, Kitahara O, Ikegami T, Endo S, Kitada C, Ogi K, Onda H, Fujino M, Shirakawa M, Nat Struct Biol 2001 Feb;8(2):161-5. PMID: 11175907 ...
A free platform for explaining your research in plain language, and managing how you communicate around it - so you can understand how best to increase its impact.
Looks for amino acid and/or nucleotide patterns and/or small ligands coordinated to a given prosthetic centre. Files have to be in the local file system and contain proper extension.. ...
Note that if all you are doing is simulating some weird ligand in water, or some weird ligand with a normal protein, then the above is more work than generating a standalone .itp file containing a [moleculetype] (for example, by modifying the .top produced by some parameterization server), and inserting an #include of that .itp file into a .top generated for the system without that weird ligand.. ...
A free platform for explaining your research in plain language, and managing how you communicate around it - so you can understand how best to increase its impact.
... Column Selection - Variety Gives You The Power Of Optimization Rezex columns utilize different ligands.
EGFR is the cell-surface receptor for members of the epidermal growth factorfamily (EGF-family) of extracellular protein ligands.
This form allows you to request diffs between any two revisions of this file. For each of the two "sides" of the diff, select a symbolic revision name using the selection box, or choose Use Text Field and enter a numeric revision. ...
This form allows you to request diffs between any two revisions of this file. For each of the two "sides" of the diff, select a symbolic revision name using the selection box, or choose Use Text Field and enter a numeric revision. ...
We perform a large-scale study of intrinsically disordered regions in proteins and protein complexes using a nonredundant set of hundreds of different protein complexes. has been associated with particular functions including cell regulation; signaling; and protein, DNA, and ligand binding. Many proteins are intrinsically disordered in native form and fold upon binding, following the conventional […]. ...
Inorganic self-assembly through sequential complexation in the formation of bimetallic and trimetallic architectures from multisite ligands based on 5,5-disubstituted 2,2-bipyridines ...
Atomically precise gold nanoclusters are ideal model catalysts with well-defined compositions and tunable structures. Determination of the ligand effect on catalysis requires the use of gold nanoclusters with protecting ligands as the only variable. Two isostructural Au38 nanoclusters, [Au38(L)20(Ph3P)4]2+ (L = alkynyl or thiolate), have been synthesized by a direct reduction method, and they have an unprecedented face-centered cubic (fcc)-type Au34 kernel surrounded by 4 AuL2 staple motifs, 4 Ph3P, and 12 bridging L ligands. The Au34 kernel can be derived from the fusion of two fcc-type Au20 via sharing a Au6 face. Catalytic performance was studied with these two nanoclusters supported on TiO2 (1/TiO2 and 2/TiO2) as catalysts. The alkynyl-protected Au38 are very active (,97%) in the semihydrogenation of alkynes (including terminal and internal ones) to alkenes, whereas the thiolated Au38 showed a very low conversion (,2%). This fact suggests that the protecting ligands play an important role in ...
Protein-ligand binding site prediction from a 3D protein structure plays a pivotal role in rational drug design and can be helpful in drug side-effects prediction or elucidation of protein function. Embedded within the binding site detection problem is the problem of pocket ranking - how to score and sort candidate pockets so that the best scored predictions correspond to true ligand binding sites. Although there exist multiple pocket detection algorithms, they mostly employ a fairly simple ranking function leading to sub-optimal prediction results. We have developed a new pocket scoring approach (named PRANK) that prioritizes putative pockets according to their probability to bind a ligand. The method first carefully selects pocket points and labels them by physico-chemical characteristics of their local neighborhood. Random Forests classifier is subsequently applied to assign a ligandability score to each of the selected pocket point. The ligandability scores are finally merged into the resulting
The Gpr1 G protein-coupled receptor regulates filamentous growth: Our studies reveal that the G protein-coupled receptor Gpr1 regulates pseudohyphal differentiation in S. cerevisiae (Figure 9). The Gpr1 receptor also regulates invasive growth of haploid strains and is required for expression of the FLO11 gene encoding a cell surface flocculin. The phenotypes of mutant strains lacking the Gpr1 receptor are similar to those of mutant strains lacking the Gα protein Gpa2, and genetic evidence supports a model in which ligand binding to the Gpr1 receptor activates Gpa2p via a direct interaction. The downstream elements of this signaling pathway consist of adenylyl cyclase, which is activated by Gpa2p to produce cAMP (Nakafukuet al. 1988; Colomboet al. 1998), resulting in activation of PKA (Figure 9). Recent studies have revealed that the Tpk2 catalytic subunit of PKA regulates pseudohyphal differentiation via the Sfl1 and Flo8 transcription factors that regulate expression of the cell surface ...
Easily label your own tag ligands & other small molecules. Mix-n-Stain™ CF® dye small ligand labeling kits are designed for rapid labeling of small (MW ~ 150 - 5,000) and relatively high affinity biological ligands (or substrates). Labeling takes about 30 minutes, without a final purification step. The ligands to be labeled must contain an aliphatic amine group that is not required for biological activity of the ligand. The amine group will form a covalent linkage with the reactive CF® dye provided in the kit. For example, suitable ligands or substrates include SNAP-tag®, CLIP-tag™ and HaloTag® ligands with an aliphatic amine. Many other small ligands are also possible candidates if they meet the criteria described above.. Simply mix your small molecule ligand with the reaction buffer and the optimally formulated dye provided, and incubate for 30 minutes, followed by a brief 5 minute quenching step. No reactive Mix-n-Stain™ dye is available at the end of labeling; therefore the ...
Studies to date have shown that EGFR activation by GPCRs represents a paradigm of potential cross-talk between tyrosine kinase receptors and GPCRs (31) . Although the biological significance of the initial studies performed in fibroblasts was undetermined, subsequent investigations in cancer cells have shown that activation of EGFR by GPCR ligands leads to downstream MAPK activation, tumor cell invasion, and DNA synthesis (13 , 32) . We previously reported that HNSCC cell lines and tissues express increased levels of GRP and GRPR when the levels of GRPR in the primary tumor were correlated with patient survival (16) . Additional investigation showed that blockade of GRP using the neutralizing antibody 2A11 inhibited HNSCC growth in vitro and in vivo, thus implicating an autocrine regulatory pathway involving this GPCR ligand and receptor in HNSCC (16) . The importance of EGFR up-regulation in HNSCC carcinogenesis has been well documented (5 , 6 , 33 , 34) . Additional investigation showed that ...
BioAssay record AID 353554 submitted by ChEMBL: Inhibition of DHT binding to human recombinant androgen receptor ligand binding domain at 15 uM by fluorescence polarization.
The results of the present work showed that administration of ERα-subtype-selective ligand PPT (Stauffer et al. 2000) in ovariectomized rats had oestrogen activity on all parameters of gonadotrope function analysed, whereas administration of ERβ-subtype-selective ligand DPN (Meyers et al. 2001) mimicked all actions of PPT except the reduction of pituitary content and serum concentration of LH. The latter action, however, was the only one not affected when both ER ligands were administered simultaneously. Morphological parameters of gonadotrope function evaluated were qualitative characteristics of the membrane-enclosed intracellular organelles, gonadotrope size, and PR expression status. In fact, due to the pivotal role of PR in gonadotrope function in the rat (Fink 2000), we used the immunohistochemical expression of PR in gonadotropes to classify them as activated (with PR expression) or hypertrophied (without PR expression).. In the rat, the presence of PR in gonadotropes is an absolute ...
Conference Call Ligand management will host a conference call today beginning at 4:30 p.m. Eastern time (1:30 p.m. Pacific time) to discuss this announcement and answer questions. To participate via telephone, please dial (877) 407-4019 from the U.S. or (201) 689-8337 from outside the U.S., using the passcode "Ligand." A replay of the call will be available until June 4, 2010 at 5:30 p.m. Eastern time by dialing (877) 660-6853 from the U.S. or (201) 612-7415 from outside the U.S. The account number is 361 and the passcode is 349820. Individual investors can access the Webcast through Ligands web site at www.ligand.com. Ligand Analyst Day Ligand will hold an Analyst Day event on June 24, 2010 in New York City. Ligand will announce full details regarding the event including program agenda by the end of May. Additional event details and webcast information will be posted closer to the event on Ligands investor Web site at www.ligand.com. About Ligand Pharmaceuticals Ligand discovers and develops ...
5-iodo-3-(2(S)-azetidinylmethoxy)pyridine (5-iodo-A-85380) and labeled it with 125I and123I. Here we present the results of experiments characterizing this radioiodinated ligand in vitro. The affinity of 5-[125I]iodo-A-85380 for α4β2 nAChRs in rat and human brain is defined by K d values of 10 and 12 pM, respectively, similar to that of epibatidine (8 pM). In contrast to epibatidine, however, 5-iodo-A-85380 is more selective in binding to the α4β2 subtype than to other nAChR subtypes. In rat adrenal glands, 5-iodo-A-85380 binds to nAChRs containing α3 and β4 subunits with 1/1000th the affinity of epibatidine, and exhibits 1/60th and 1/190th the affinity of epibatidine at α7 and muscle-type nAChRs, respectively. Moreover, unlike epibatidine and cytisine, 5-[125I]iodo-A-85380 shows no binding in any brain regions in mice homozygous for a mutation in the β2 subunit of nAChRs. Binding of 5-[125I]iodo-A-85380 in rat brain is reversible, and is characterized by high specificity and a slow rate ...
Kevin Pfleger (University of Western Australia) talks about his experience with BRET-based ligand binding on BMG LABTECH Microplate readers. Watch here.
OPUS (Open Publications of UTS Scholars) is the UTS institutional repository. It showcases the research of UTS staff and postgraduate students to a global audience. For you, as a researcher, OPUS increases the visibility and accessibility of your research by making it openly available regardless of where you choose to publish.. Items in OPUS are enhanced with high quality metadata and seeded to search engines such as Google Scholar as well as being linked to your UTS research profile, increasing discoverability and opportunities for citation of your work and collaboration. In addition, works in OPUS are preserved for long-term access and discovery.. The UTS Open Access Policy requires UTS research outputs to be openly available via OPUS. Depositing your work in OPUS also assists you in complying with ARC, NHMRC and other funder Open Access policies. Providing Open Access to your research outputs through OPUS not only ensures you comply with these important policies, but increases opportunities ...
The hematopoietic compartment is one of the most severely damaged after chemotherapy, radiotherapy or accidental irradiations. Whatever its origin, the resulting damage to the bone marrow remains difficult to evaluate. Thus, it would be of great interest to get a biological indicator of residual hematopoiesis in order to adapt the treatment to each clinical situation. Recent results indicated that the plasma Flt3 ligand concentration was increased in patients suffering from either acquired or induced aplasia, suggesting that Flt3 ligand might be useful as a biological indicator of bone marrow status. We thus followed in a mouse model as well as in several clinical situations the variations in plasma Flt3 ligand concentration, after either homogeneous or heterogeneous irradiations. These variations were correlated to the number of hematopoietic progenitors and to other parameters such as duration and depth of pancytopenia ...
diss/z2006/0801 Prediction of protonation states in ligand-protein complexes upon ligand binding Recent hardware development increase the computing power, in consequence many biological and chemical processes can now be successfully modelled in a way which was not to imagine 20 years ago. Examples of such processes are molecular dynamics studies of large biomolecules, the prediction of free energy of binding for protein-ligand complexes, investigations of reaction paths in enzymes, to mention only a few. One issue which is still unresolved concerns the accurate estimation of protonation states in protein-ligand complexes. In this thesis, we present the development of a novel charge assignment procedure named PEOE_PB (Partial Equalisation of Orbital Electronegativities - optimized for Poisson-Boltzmann calculations), which represents a method for the assignment of atomic partial charges. It works reliably with both proteins and small organic molecules using a consistent approach. Such charges are ...
Title:Class A GPCRs: Structure, Function, Modeling and Structure-based Ligand Design. VOLUME: 23 ISSUE: 29. Author(s):Xiaojing Cong*, Jeremie Topin and Jerome Golebiowski*. Affiliation:Institute of Chemistry - Nice, UMR 7272 CNRS - University Nice - Sophia Antipolis, 06108 Nice cedex 2, Institute of Chemistry - Nice, UMR 7272 CNRS - University Nice - Sophia Antipolis, 06108 Nice Cedex 2, Institute of Chemistry - Nice, UMR 7272 CNRS - University Nice - Sophia Antipolis, 06108 Nice cedex 2. Keywords:GPCR, ligand design, allosteric modulation, ligand bias, homology modeling, molecular dynamics.. Abstract:G protein-coupled receptors (GPCRs), especially the class A, are the most heavily investigated drug targets in the pharmaceutical industry. Tremendous efforts have been made by both industry and academia to understand the molecular structure and function of this large family of transmembrane proteins. Our understanding in GPCR activation has evolved from the classical inactive-active two-state ...
Our study demonstrates for the first time that treatment with RTL after onset of MCAO reduces cortical and total infarct size, inhibits infiltrating inflammatory cells, particularly activated macrophages/microglial cells and DCs, into postischemic brain, and partially preserves spleen cell numbers that are typically ablated after MCAO. This result was specific to RTL551 treatment in C57BL/6 male mice and verified using a "humanized" RTL1000 construct to treat MCAO in HLA-DR2-Tg mice. The results clearly show that the therapeutic activity of RTL requires a neuroantigen peptide (mouse or human MOG-35-55) tethered to an MHC moiety that closely matches the Class II of the treated mouse strain (I-Ab for C57BL/6 mice and HLA-DR2 for DR2-Tg mice). In contrast, treatment of C57BL/6 mice with RTL553 comprised of I-Ab coupled to I-Ea-52-68 (a nonneuroantigen peptide) and RTL342M comprised of HLA-DR2 (nonmatched MHC Class II) coupled to mMOG-35-55 peptide did not have therapeutic effects.. Beyond the ...
Tyrosine phosphorylation plays a critical role in the control of many cellular processes including cell proliferation, differentiation, metabolism, as well as cell survival and migration. Receptor tyrosine kinases undergo ligand dependent dimerization which activates their intrinsic protein tyrosine kinase (PTK) domains. We have determined the crystal structure of Stem cell factor (SCF) and fibroblast growth factor (FGF), two ligands of receptor tyrosine kinases. In addition, we have determined the crystal structure of FGF in complex with the extracellular ligand binding domain of FGF-receptor (FGFR) and with a heparin sulfate oligosacchride. The structure of the ternary FGF/heparin/FGFR complex provides a molecular view of how FGF acts in concert with heparin to induce the dimerization and activation of FGF-receptors. We have also determined the crystal structure of the catalytic PTK domain of FGFR in complex with an ATP analogue or in complex with specific PTK inhibitors of FGFR activity and ...
It has been suggested that receptor-ligand complexes segregate or co-localise within immune synapses according to their size, and this is important for receptor signaling. Here, we set out to test the importance of receptor-ligand complex dimensions for immune surveillance of target cells by human Natural Killer (NK) cells. NK cell activation is regulated by integrating signals from activating receptors, such as NKG2D, and inhibitory receptors, such as KIR2DL1. Elongating the NKG2D ligand MICA reduced its ability to trigger NK cell activation. Conversely, elongation of KIR2DL1 ligand HLA-C reduced its ability to inhibit NK cells. Whereas normal-sized HLA-C was most effective at inhibiting activation by normal-length MICA, only elongated HLA-C could inhibit activation by elongated MICA. Moreover, HLA-C and MICA that were matched in size co-localised, whereas HLA-C and MICA that were different in size were segregated. These results demonstrate that receptor-ligand dimensions are important in NK ...
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The goal of our ligand-centric approach is to facilitate discovery of protein function by providing detailed information about ligand binding sites and ligand-specific binding motifs, aiding in structure-based modeling efforts and helping crystallographers identify unexpected molecular commonalities and similarities with other protein-ligand systems.. Carrying out comparative analysis on binding sites of similar ligands yields valuable information about conserved and non-conserved interactions. While the conserved interactions are determinants of ligand affinity, the non-conserved interactions govern the specificity. For example, similarities between the ligand binding sites of an odorant receptor and metabotropic glutamate receptors defined the motif for ligand recognition in the G-protein coupled receptor superfamily [52]. Our ligand conformational and classification analysis will aid in choosing the right conformation of the ligand for docking studies. For example, if only an unbound ...
An increasing number of therapeutic antibodies targeting tumors that express the epidermal growth factor receptor (EGFR) are in clinical use or late stages of clinical development. Here we investigate the molecular basis for inhibition of EGFR activation by the therapeutic antibody matuzumab (EMD72000). We describe the X-ray crystal structure of the Fab fragment of matuzumab (Fab72000) in complex with isolated domain III from the extracellular region of EGFR. Fab72000 interacts with an epitope on EGFR that is distinct from the ligand-binding region on domain III and from the cetuximab/Erbitux epitope. Matuzumab blocks ligand-induced receptor activation indirectly by sterically preventing the domain rearrangement and local conformational changes that must occur for high-affinity ligand binding and receptor dimerization. Matuzumab binding to EGFR prevents the conformational rearrangement required for dimerization.,Schmiedel J, Blaukat A, Li S, Knochel T, Ferguson KM Cancer Cell. 2008 ...
The Notch receptor is part of a core signalling pathway which is highly conserved in all metazoan species. It is required for various cell fate decisions at multiple stages of development and in the adult organism, with dysregulation of the pathway associated with genetic and acquired diseases including cancer. Although cellular and in vivo studies have provided considerable insight into the downstream consequences of Notch signalling, relatively little is known about the molecular basis of the receptor/ligand interaction and initial stages of activation. Recent advances in structure determination of the extracellular regions of human Notch-1 and one of its ligands Jagged-1 have given new insights into docking events occurring at the cell surface which may facilitate the development of new highly specific therapies. We review the structural data available for receptor and ligands and identify the challenges ahead.
Neurodegenerative diseases feature neurochemical and neuropathological changes which are intimately linked with excitotoxicity. PSD-95 a post-synaptic scaffold protein of the NMDA receptor complex, containing PDZ domains coupling to a PMCa2B calcium channel, NMDAR2, and i-nos, has been found to mediate Glutamate induced excitotoxicity. Neuronal damage may be mediated by calcium intrusion and oxidative stress and PSD-95 is a potential therapeutic target. PDZ binding ligands have been designed based on the C-terminal sequence of the PMCa2b calcium channel sub-unit in order to disrupt its interaction with PSD95 via PDZ domain 1. Current PDZ binding ligands currently have Kd constants in the micromolar range and tighter binding is required (Kd constants in nanomolar range) for therapeutic use. Structural alterations have been proposed by various researchers to this end including cyclisation of PDZ peptide ligands. Putative PDZ binding ligands were modeled in Silico based on existing structures but ...
Chemical Thermodynamics of Compounds and Complexes of U, Np, Pu, Am, Tc, Se, Ni and Zr With Selected Organic Ligands Physics Science Ebook by Wolfgang Hummel, Federico J. Mompean, Myriam IllemassèNe, Myriam Illemassne,
Serotonin or 5-hydroxytryptamine subtype 2C (5-HT2C) receptor belongs to class A amine subfamily of Gprotein- coupled receptor (GPCR) super family and its ligands has therapeutic promise as anti-depressant and -obesity agents. So far, bovine rhodopsin from class A opsin subfamily was the mostly used X-ray crystal template to model this receptor. Here, we explained homology model using beta 2 adrenergic receptor (β2AR), the model was energetically minimized and validated by flexible ligand docking with known agonists and antagonists. In the active site Asp134, Ser138 of transmembrane 3 (TM3), Arg195 of extracellular loop 2 (ECL2) and Tyr358 of TM7 were found as important residues to interact with agonists. In addition to these, V208 of ECL2 and N351 of TM7 was found to interact with antagonists. Several conserved residues including Trp324, Phe327 and Phe328 were also found to contribute hydrophobic interaction. The predicted ligand binding mode is in good agreement with published mutagenesis and ...
Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 4. Protein Tyrosine Kinase (PTK) family; Fibroblast Growth Factor Receptor 4 (FGFR4); catalytic (c) domain. The PTKc family is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, and phosphoinositide 3-kinase (PI3K). PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. FGFR4 is part of the FGFR subfamily, which are receptor tyr kinases (RTKs) containing an extracellular ligand-binding region with three immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of FGFRs to their ligands, the FGFs, results in receptor dimerization and activation, and intracellular signaling. The binding of FGFs to FGFRs is promiscuous, in that a receptor may be activated by several ligands and a ligand may bind to more that one type of ...
Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 2. Protein Tyrosine Kinase (PTK) family; Fibroblast Growth Factor Receptor 2 (FGFR2); catalytic (c) domain. The PTKc family is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, and phosphoinositide 3-kinase (PI3K). PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. FGFR2 is part of the FGFR subfamily, which are receptor tyr kinases (RTKs) containing an extracellular ligand-binding region with three immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of FGFRs to their ligands, the FGFs, results in receptor dimerization and activation, and intracellular signaling. The binding of FGFs to FGFRs is promiscuous, in that a receptor may be activated by several ligands and a ligand may bind to more that one type of ...
This is a pretty good hit rate. Generally virtual screening campaigns are lucky to have a hit rate of a few percent. Curiously, the authors also found a similarly high hit rate during a past VS campaign against the well-known β2 adrenergic receptor. What could be responsible for this high hit rate against GPCRs? The reasons are interesting. One reason could be that GPCRs are very well adapted to bind small molecules in compact pockets, enclosing them and forming many kinds of productive interactions. But more intriguingly, as the authors have noted earlier, there is "biogenic bias" in favor of certain target-specific chemotypes in commercial libraries that are screened, both during VS as well as HTS. This in turn reflects the biases of medicinal chemists in picking and synthesizing certain kinds of chemotypes based on the importance of drug targets and past successes in hitting these targets. GPCRs clearly are enormously important, and GPCR-friendly ligand chemotypes thus constitute a large ...
The modification of medical device surface with adhesive ligands has been recently shown to be an effective means for making a bioselective surface which can inhibit bacterial adhesion while promoting host cell adhesion on device materials. Currently, the lack of quantitative correlation between the adhesion strength of bacteria, nature of adhesive ligand and adhesion kinetics of mammalian cells hinders the development of such device surface. In this study, the biophysical responses of bacteria and mammalian cells towards adhesive ligand on model device surfaces formed by the chemisorption of dopamine (a moderate antibiotic) on glass are elucidated. The effects of RGD, collagen and dopamine modification on the adhesion strength of two clinically significant bacteria including Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) were investigated by the determination of minimum lateral forces for bacterial detachment and the density of adhering bacteria. The result indicates that RGD ...
Factors that govern specificity-promiscuity will be examined using an ensemble of ligand-receptor systems that span a specificity-affinity continuum. Through the comparative analyses of the structurally homologous protein-ligand pairs, factors that influence specificity will be illuminated as enhancing features will become enriched and diminishing ones will be "washed away," thus providing deeper understanding of how the structural properties of ligand pockets relates to ligand-binding properties. The ensemble will be derived from the BmrR transcription factor, which recognizes numerous structurally unrelated cationic lipophilic ligands and regulates the expression of a multidrug efflux pump. A convergent molecular library will be generated using phage display and biopanning selective pressures designed to enforce increases in binding specificity and affinity. The binding properties of the variants will be characterized using thermodynamic, kinetic, and structural methods. Some specific issues ...
The mechanism by which low affinity adhesion molecules function to produce stable cell-cell adhesion is unknown. In solution, the interaction of human CD2 with its ligand CD58 is of low affinity (500 mM-1) and the interaction of rat CD2 with its ligand CD48 is of still lower affinity (40 mM-1). At the molecular level, however, the two systems are likely to be topologically identical. Fluorescently labeled glycosylphosphatidylinositol-anchored CD48 and CD58 were prepared and incorporated into supported phospholipid bilayers, in which the ligands were capable of free lateral diffusion. Quantitative fluorescence imaging was used to study the binding of cell surface human and rat CD2 molecules to the fluorescent ligands in contact areas between Jurkat cells and the bilayers. These studies provide two major conclusions. First, CD2/ligand interactions cooperate to align membranes with nanometer precision leading to a physiologically effective two-dimensional affinity. This process does not require the intact
Denticity (represented by κ) refers to the number of times a ligand bonds to a metal through noncontiguous donor sites. Many ligands are capable of binding metal ions through multiple sites, usually because the ligands have lone pairs on more than one atom. Ligands that bind via more than one atom are often termed chelating. A ligand that binds through two sites is classified as bidentate, and three sites as tridentate. The "bite angle" refers to the angle between the two bonds of a bidentate chelate. Chelating ligands are commonly formed by linking donor groups via organic linkers. A classic bidentate ligand is ethylenediamine, which is derived by the linking of two ammonia groups with an ethylene (−CH2CH2−) linker. A classic example of a polydentate ligand is the hexadentate chelating agent EDTA, which is able to bond through six sites, completely surrounding some metals. The number of times a polydentate ligand binds to a metal centre is symbolized by "κn", where n indicates the number ...
Title: ParDOCK: An All Atom Energy Based Monte Carlo Docking Protocol for Protein-Ligand Complexes. VOLUME: 14 ISSUE: 7. Author(s): A. Gupta, A. Gandhimathi, P. Sharma and B. Jayaram. Affiliation:Dept. of Chemistry&Supercomputing Facility for Bioinformatics&Computational Biology, Indian Institute of Technology, Hauz Khas, New Delhi-110016, India.. Keywords:Energy based scoring, Computer aided drug design (CADD), Monte Carlo docking, Binding affinity, Cluster computing.. Abstract: We report here an all-atom energy based Monte Carlo docking procedure tested on a dataset of 226 proteinligand complexes. Average root mean square deviation (RMSD) from crystal conformation was observed to be ∼ 0.53 Å. The correlation coefficient (r2) for the predicted binding free energies calculated using the docked structures against experimental binding affinities was 0.72. The docking protocol is web-enabled as a free software at www.scfbioiitd. res.in/dock. ...
Glucagon-like peptide-1 (GLP-1) is a key incretin peptide that promotes insulin secretion in response to nutrient ingestion, but also has a range of other actions including preservation of b-cell mass, reduction in gastric emptying and reduction in appetite that make it a desirable target for treatment of type II diabetes. GLP-1 exerts its effects by binding to the GLP-1 receptor (GLP-1R), a Class B G protein-coupled receptor (GPCR). In recent years, it has become clear that individual GPCRs can exist in multiple receptor conformations and can elicit numerous functional responses, both G protein- and non-G protein-mediated. This has led to the discovery that different ligands can stabilize distinct subsets of receptor conformations that can "traffic" stimulus to diverse functional outputs with varying prominence, a concept referred to as biased agonism (also known as functional selectivity, stimulus bias or ligand-directed signaling). I will discuss the concept of ligand-directed signal bias as ...
In the Au34 kernel of 1, the Au-Au distances from the four centered Au atoms (fig. S4B, highlighted in pink) to the peripheral Au atoms can be classified into two groups: shorter distances ranging from 2.7325(12) to 2.9138(9) Å and longer ones ranging from 2.9493(11) to 3.3017(12) Å with an average distance of 2.925 Å. It is comparable to the average Au-Au distance of 2.926 Å in 2. The Au-Au distances of the peripheral Au atoms range from 2.6992(11) to 2.8340(2) Å and 2.9085(12) to 3.4160(12) Å, giving an average distance of 2.940 Å. A comparable average distance of 2.958 Å is found in 2. The average Au-Au distances of Au34 kernel in 1 and 2 are 2.940 and 2.946 Å, respectively, which are slightly longer than the 2.88 Å bond length in bulk gold, indicating that the interaction between Au atoms in Au34 is strong. The four Au atoms of staples are linked to the double Au20 cores, with an average Au-Au distance of 3.147 Å for 1 and 3.217 Å for 2. As shown in Fig. 3 (A and E), the SR ...
see article for more reactions. Abstract. The stereochemical outcome of Negishi coulings of Z-alkenyl halides is highly ligand dependent. A modified method solves the stereochemical issue and significantly improves yields of Negishi couplings in general even at ambient temperature.. ...
The characterization of protein stability changes and protein-ligand interactions on the proteomic scale is important for understanding the biology of cellular processes. The identification and quantification of protein-ligand binding affinities is critical for disease state analyses and drug discovery. A mass spectrometry-based technique, Stability of Proteins from Rates of Oxidation (SPROX), has been established for the thermodynamic analysis of protein stability and protein-ligand interactions. In the first part of this dissertation, a previously published iTRAQ-SPROX protocol is improved by incorporating a filter assisted sample preparation (FASP) protocol to significantly reduce sample loss during the experiment. Also, in order to eliminate methionine as a potential contaminant that can cause signal suppression during LC-MS/MS analysis, TCEP•HCl is used to quench the H2O2 oxidation instead of methionine. This avoids the potential reaction between the free methionine and the iTRAQ ...
NOTCH1 is known as an oncogenic or tumor suppressive gene in solid cancer. NOTCH1 mutations in oral squamous cell carcinoma (OSCC) frequently occur near the ligand-binding region. These mutations change the domain structure of this protein and affect the ligand binding activity. When NOTCH1 is activated by ligand binding, NOTCH1 intracellular domain (NICD) is cleaved from the cell membrane. This study investigated the functional change induced by a NOTCH1 mutation detected in OSCC clinical samples using stable transformant analysis. HEK293 cell lines expressing NOTCH1 wild-type (WT cells) or p.A465T NOTCH1 (A465T cells) were established. NOTCH1 expression was analyzed by flow cytometry, western blotting, and immunofluorescence using an anti-human NOTCH1 antibody. mRNA expression levels in WT and A465T cells were determined by quantitative real-time PCR (qPCR). Cell proliferation was analyzed by using cell growth assays and a xenograft tumor assay. Flow cytometry indicated that NOTCH1 expression ...
TY - JOUR. T1 - G protein-coupled receptor Gpr4 senses amino acids and activates the cAMP-PKA pathway in Cryptococcus neoformans. AU - Xue, Chaoyang. AU - Bahn, Yong Sun. AU - Cox, Gary M.. AU - Heitman, Joseph. PY - 2006/2/1. Y1 - 2006/2/1. N2 - The Gα protein Gpa1 governs the cAMP-PKA signaling pathway and plays a central role in virulence and differentiation in the human fungal pathogen Cryptococcus neoformans, but the signals and receptors that trigger this pathway were unknown. We identified seven putative proteins that share identity with known G protein-coupled receptors (GPCRs). One protein, Gpr4, shares limited sequence identity with the Dictyostelium discoideum cAMP receptor cAR1 and the Aspergillus nidulans GPCR protein GprH and also shares structural similarity with the Saccharomyces cerevisiae receptor Gpr1. gpr4 mutants exhibited reduced capsule production and mating defects, similar to gpa1 mutants, and exogenous cAMP suppressed both gpr4 mutant phenotypes. Epistasis analysis ...
TY - JOUR. T1 - Effects of μ- and δ-opioid receptors ligands on rhythm and contractility disorders of isolated rat heart in postischemic period. AU - Maslov, L. N.. AU - Lishmanov, Yu B.. PY - 1998. Y1 - 1998. N2 - Selective μ-opioid receptor agonist DAGO increased tolerance of isolated perfused rat heart to total ischemia (45 min) and reperfusion (60 min). Intravenous administration of DAGO (0,1 mg/kg) before of the heart isolation or direct pertusion by a solution containing DAGO (1 mg/l) prior of ischemia induction prevented reperfusion arrhythmias and subpression of cardiac contractility but had no effect on magnitude of contracture. Selective δ-opioid receptor agonist DSLET did not affect arrhythmias and cardiac contractility during postischemic period.. AB - Selective μ-opioid receptor agonist DAGO increased tolerance of isolated perfused rat heart to total ischemia (45 min) and reperfusion (60 min). Intravenous administration of DAGO (0,1 mg/kg) before of the heart isolation or ...
The CdSe quantum dots (QDs) with bidentate ligands: a-diimine (NN) and dihydrolipoic acid (DHLA) were synthesized and characterized by UV-Vis, particle size and capillary electrophoretic techniques. Two systems were analyzed: CdSe with one ligand (CdSe/ligand) and CdSe with two different ligands (CdSe//ligand1/ligand2), where ligand = α-diimine or DHLA. Hydrodynamic features of functionalized QDs were characterized by zone capillary electrophoretic (CZE), and particle size techniques and these methods were consistent. It was established that CZE, micellar (MEKC) and microemulsion (MEEKC) modes were suitable for separating charged CdSe QDs and that no peaks were obtained for QDs passivated with electrically neutral ligands. For CdSe QDs with neutral (NN) ligands, a preconcentration method with the use of a micellar plug was introduced for visualizing these QDs. A sharp peak representing neutral QDs was obtained within the zone of micellar plug of a non-ionic surfactant, Here, a ligand character ...
The Eph family is the largest family of receptor tyrosine kinases, at least, 14 different Eph kinases have been identified so far[1, 2]. These receptors can be divided into two subclasses (EphB and EphA) based on the cell surface ligand which they interact with. Ligands that interact with EphA receptors are generally attached to the cell surface via glycosylphosphatidylinositol (ephrinA ligands), while ligands that activate EphB receptors are transmembrane proteins (ephrinB ligands)[1, 2]. Eph receptor kinases and their ligands (ephrins) play a critical role in embryonic patterning, angiogenesis and neuronal targeting[2-4]. In the nervous system, EphB receptor kinases are enriched at excitatory synapses and are important during synapse and spine formation and maintenance[2].. Adaptor proteins, composed almost entirely of well-defined interaction domains, serve to link two functional members of a signaling pathway[5]. Nck family of adaptors comprising of SH2 and SH3 domains are implicated in the ...
CD1d-restricted natural killer T cells (NKT cells) possess a wide range of effector and regulatory activities that are related to their ability to secrete both T helper 1 (Th1) cell- and Th2 cell-type cytokines. We analyzed presentation of NKT cell activating α galactosylceramide (αGalCer) analogs that give predominantly Th2 cell-type cytokine responses to determine how ligand structure controls the outcome of NKT cell activation. Using a monoclonal antibody specific for αGalCer-CD1d complexes to visualize and quantitate glycolipid presentation, we found that Th2 cell-type cytokine-biasing ligands were characterized by rapid and direct loading of cell-surface CD1d proteins. Complexes formed by association of these Th2 cell-type cytokine-biasing αGalCer analogs with CD1d showed a distinctive exclusion from ganglioside-enriched, detergent-resistant plasma membrane microdomains of antigen-presenting cells. These findings help to explain how subtle alterations in glycolipid ligand structure can ...
Ligands[edit]. Ligands containing a chiral 2-oxazoline ring are used in asymmetric catalysis due to their facile synthesis, ... Trisoxazolinylborate ligands. Polymers[edit]. 2-Oxazolines, such as 2-ethyl-2-oxazoline, can undergo living cationic ring- ... McManus, Helen A.; Guiry, Patrick J. (2004). "Recent Developments in the Application of Oxazoline-Containing Ligands in ... Hargaden, Gráinne C.; Guiry, Patrick J. (2009). "Recent Applications of Oxazoline-Containing Ligands in Asymmetric Catalysis". ...
Phosphine ligands are usually "spectator" rather than "actor" ligands. They generally do not participate in reactions, except ... also function as ligands. Such ligands are less basic and have small cone angles. These complexes are susceptible to ... 1973). Transition Metal Complexes of Phosphorus, Arsenic, and Antimony Ligands. J. Wiley. ISBN 0-470-58117-4. .. . ... Phosphine ligands are also π-acceptors. Their π-acidity arises from overlap of P-C σ* anti-bonding orbitals with filled metal ...
Ligand[edit]. The primary ligand for P-selectin is P-selectin glycoprotein ligand-1 (PSGL-1) which is expressed on almost all ... However, PSGL-1 is not specific for P-selectin, as it can also function as a ligand for both E- and L-selectin.[17] ... Ligands for P-selectin on eosinophils and neutrophils are similar sialylated, protease-sensitive, endo-beta-galactosidase- ... Vestweber D, Blanks JE (January 1999). "Mechanisms that regulate the function of the selectins and their ligands". Physiol. Rev ...
Binding for ligands other than oxygen[edit]. Besides the oxygen ligand, which binds to hemoglobin in a cooperative manner, ... hemoglobin ligands also include competitive inhibitors such as carbon monoxide (CO) and allosteric ligands such as carbon ... A sixth position can reversibly bind oxygen by a coordinate covalent bond,[39] completing the octahedral group of six ligands. ... and fungi all have hemoglobin-like proteins whose known and predicted roles include the reversible binding of gaseous ligands. ...
Ligand chemistry[edit]. Water's Lewis base character makes it a common ligand in transition metal complexes, examples of which ... In solid hydrates, water can be either a ligand or simply lodged in the framework, or both. Thus, FeSO. 4·7H. 2O consists of [ ... Fe2(H2O)6]2+ centers and one "lattice water". Water is typically a monodentate ligand, i.e., it forms only one bond with the ...
Ligands[edit]. A number of ligands for FXR are known, of both natural and synthetic origin.[11][12][13] ... ligand-dependent nuclear receptor binding. • transcription factor activity, RNA polymerase II distal enhancer sequence-specific ... Chenodeoxycholic acid and other bile acids are natural ligands for FXR. Similar to other nuclear receptors, when activated, FXR ... RNA polymerase II transcription factor activity, ligand-activated sequence-specific DNA binding. • bile acid receptor activity ...
Ligands[edit]. Two of the primary active constituents responsible for the antidepressant and anxiolytic benefits of Hypericum ...
Ligands[edit]. GPER binds estradiol though not other endogenous estrogens, such as estrone or estriol, nor for other endogenous ...
Selective ligands[edit]. A number of selective ligands are available for NK3. NK3 receptor antagonists are being investigated ... Neurokinin B - endogenous peptide ligand, also interacts with other neurokinin receptors but has highest affinity for NK3 ... "Expression cloning of cDNA encoding a seven-helix receptor from human placenta with affinity for opioid ligands". Proceedings ...
The metal to ligand chemical bond is largely ionic. Ligands[edit]. Most organoscandium compounds have at least one ... 2 two allyl ligands are η3 coordinated and one allyl ligand is η1 coordinated. ... Chlorine can be replaced by a host of other ligands for example by an allyl group in reaction with allylmagnesium bromide: ScCp ... Cp2ScX compounds are dimers with X forming a bridging ligand. Dimerization is avoided in presence of coordinating solvent such ...
One of the ligands phenyl-groups can be replaced by propene, and the resulting diphenylpropylphosphine ligand can inhibit the ... Catalyst and ligands[edit]. The triphenylphosphine complexes are under reaction conditions potentially subject to hydrogenation ... Using chiral phosphine ligands, the hydroformylation can be tailored to favor one enantiomer.[11] Thus, for example, ... Bulky ligands exacerbate this steric hindrance. Hence, the mixed carbonyl/phosphine complexes offer a greater selectivity for ...
Many complexes feature coordination bonds between a metal and organic ligands. The organic ligands often bind the metal through ... However, if any of the ligands form a direct M-C bond, then complex is usually considered to be organometallic, e.g., [(C6H6)Ru ... For highly electropositive elements, such as lithium and sodium, the carbon ligand exhibits carbanionic character, but free ... refers to metal-containing compounds lacking direct metal-carbon bonds but which contain organic ligands. Metal β-diketonates, ...
... pyridine-based dopamine D4 receptor ligands: discovery of an inverse agonist radioligand for PET". Journal of Medicinal ... azines as selective D4-ligands. Induction of penile erection by 2-[4-(2-methoxyphenyl)piperazin-1-ylmethyl]imidazo[1,2-a] ...
Ligands[edit]. Activating ligands[edit]. The following standard prostaglandins have the following relative affinities and ... Inhibiting ligands[edit]. The following compounds are selective receptor antagonists of and thereby inhibit the activation of ... Ligands that activate DP2 stimulate the in vitro chemotaxis (i.e. directed migration) of leukocytes active in mediating ... G protein-coupled receptors (GPCRs) such as DP2 are integral membrane proteins that, when bound by their cognate ligands (or, ...
Many ligand transport proteins bind particular small biomolecules and transport them to other locations in the body of a ... The canonical example of a ligand-binding protein is haemoglobin, which transports oxygen from the lungs to other organs and ... These proteins must have a high binding affinity when their ligand is present in high concentrations, but must also release the ... Transmembrane proteins can also serve as ligand transport proteins that alter the permeability of the cell membrane to small ...
Ligands[edit]. The following is a table of selected substrates, inducers and inhibitors of CYP2C19. Where classes of agents are ...
Integrin ligands (collagens, fibrinogen, fibronectin, laminins, ICAM-1, ICAM-2, osteopontin, VCAM-1, vitronectin) ...
Selective Ligands[edit]. Several selective ligands for NK2 are now available, and although most of the compounds developed so ... Bhogal N, Donnelly D, Findlay JB (Nov 1994). "The ligand binding site of the neurokinin 2 receptor. Site-directed mutagenesis ...
Selective ligands[edit]. A range of selective ligands for the GHS-R receptor are now available and are being developed for ... One transcript, 1a, excises an intron and encodes the functional protein; this protein is the receptor for the ghrelin ligand ...
Organofluorine ligands in transition metal chemistry[edit]. Organofluorine ligands have long been featured in organometallic ... 5.7 Organofluorine ligands in transition metal chemistry *5.7.1 C-F bond activation ... The organofluorine compounds can serve as a "sigma-donor ligand," as illustrated by the titanium(III) derivative [(C5Me5)2Ti(FC ... In an area where coordination chemistry and materials science overlap, the fluorination of organic ligands is used to tune the ...
2008). "Novel High-Affinity and Selective Biaromatic 4-Substituted gamma-Hydroxybutyric Acid (GHB) Analogues as GHB Ligands: ... November 2003). "Selective gamma-hydroxybutyric acid receptor ligands increase extracellular glutamate in the hippocampus, but ...
Ligands[edit]. Antagonists. *A-315456[6]. *BMY 7378 (also α2C antagonist)[7] ...
... (abbreviated as en when a ligand) is the organic compound with the formula C2H4(NH2)2. This colorless liquid ... The salen ligands, some of which are used in catalysis, are derived from the condensation of salicylaldehydes and ... Related ligands[edit]. Related derivatives of ethylenediamine include tetramethylethylenediamine (TMEDA) and ... Ethylenediamine is a well-known bidentate chelating ligand for coordination compounds, with the two nitrogen atoms donating ...
Selective Ligands[edit]. The cholecystokinin B receptor responds to a number of ligands. ... Integrin ligands (collagens, fibrinogen, fibronectin, laminins, ICAM-1, ICAM-2, osteopontin, VCAM-1, vitronectin) ...
Ligands[edit]. Agonists[edit]. *Ergotamine (vasoconstrictor in migraine). *Oxymetazoline. *Sumatriptan (vasoconstrictor in ...
Ligands[edit]. Until comparatively recently, there were few pharmacological tools for the study of δ receptors. As a ... A showing of selective delta opioid ligands. Blue represents a common phenolic moiety, yellow a basic nitrogen, and red a ... Recent work indicates that exogenous ligands that activate the δ receptors mimic the phenomenon known as ischemic ... In the rat model, introduction of δ active ligands results in significant cardioprotection.[23] ...
Increased expression of A Proliferation-inducing Ligand (APRIL) in lung leukocytes and alveolar epithelial cells in COPD ... One of the key promoters of B cell expansion is A PRoliferation-Inducing Ligand (APRIL). APRIL has been strongly linked to non ... Increased expression of A Proliferation-inducing Ligand (APRIL) in lung leukocytes and alveolar epithelial cells in COPD ... Increased expression of A Proliferation-inducing Ligand (APRIL) in lung leukocytes and alveolar epithelial cells in COPD ...
This article is about ligands in biochemistry. For ligands in inorganic chemistry, see Ligand. For other uses, see Ligand ( ... Bivalent ligand[edit]. Bivalent ligands consist of two drug-like molecules (pharmacophores or ligands) connected by an inert ... High-affinity ligand binding implies that a relatively low concentration of a ligand is adequate to maximally occupy a ligand- ... In the example shown to the left, ligand-binding curves are shown for two ligands with different binding affinities. Ligand ...
4-1BB+Ligand at the US National Library of Medicine Medical Subject Headings (MeSH) ... 4-1BBL (4-1BB ligand) is found on APCs (antigen presenting cells) and binds to 4-1BB. ... Retrieved from "https://en.wikipedia.org/w/index.php?title=4-1BB_ligand&oldid=842807712" ...
EGF like ligands; Growth Factors Epidermal growth factor (EGF-)-like family members bind to and activate EGF receptor tyrosine ... Harris RC, Chung E, Coffey RJ (2003) EGF receptor ligands. Exp Cell Res 284:2-13CrossRefPubMedGoogle Scholar ... Wu WK, Tse TT, Sung JJ, Li ZJ, Yu L, Cho CH (2009) Expression of ErbB receptors and their cognate ligands in gastric and colon ... Dong J, Wiley HS (2000) Trafficking and proteolytic release of epidermal growth factor receptor ligands are modulated by their ...
... is concerned with the identification of ligands (drugs) that bind nucleic acids (NA) and provide users with sets of specific ... The nucleic acids and ligands database (NALD) is concerned with the identification of ligands (drugs) that bind nucleic acids ( ... classes and links to diseases may be in association with the ligands. These were calculated from entries of NA/Ligand complexes ... Bioinformatics Database Data mining Data integration Nucleic acids Binding motifs Ligands Drugs Diseases ...
Definition of addressin ligands. Provided by Stedmans medical dictionary and Drugs.com. Includes medical terms and definitions ...
ligand, pioglitazone, in rats," Redox Report, vol. 7, no. 5, pp. 294-299, 2002. View at Publisher · View at Google Scholar ... ligand, provides protection from dextran sulfate sodium-induced colitis in mice in association with inhibition of the NF-κB- ... ligand-induced apoptosis through a p53-dependent mechanism in human gastric cancer cells," Cancer Science, vol. 94, no. 4, pp. ... ligand, inhibits aspirin-induced gastric mucosal injury in rats," Alimentary Pharmacology and Therapeutics, vol. 15, no. 6, pp ...
Ligand "noninnocence" in coordination complexes vs. kinetic, mechanistic, and selectivity issues in electrochemical catalysis ...
The Eph family receptors and ligands.. Zhou R1.. Author information. 1. Laboratory for Cancer Research, College of Pharmacy, ... The Eph family is the largest of all known tyrosine kinase receptor-ligand systems. They are expressed in distinct, but ...
... N. V. Kostiuk,1 M. B. Belyakova,2 D. V. Leshchenko,2 V. V. ...
... An important aspect of simple Crystal Field Theory is the orientation of the d-orbital lobes with respect ... If you know the author of Ligand Field Theory, please help us out by filling out the form below and clicking Send. ... Note that the lobes point towards either the centres of the faces (where the ligands would sit for an octahedral complex) or ... You just viewed Ligand Field Theory. Please take a moment to rate this material. ...
Therefore, iron-haem complexes are ligands in the biochemical sense for the globin; and the oxygen is a ligand in the chemical ... providing some of its ligands.. Haem molecules occupy four ligand positions around the central iron atom, in a plane. When ...
Landis Ligands. By: William Sommer and Daniel Weibel, Aldrich ChemFiles 2008, 8.2, 84. ... Two of the essential components for highly active and selective catalysts are the ligand and the metal. Professor Landis and co ... Utilizing this newly developed ligand, Thomas and coworkers synthesized a series of oxazolines and imidazoles.1 Reacting vinyl ... Professor Landis and coworkers developed a new family of ligands based on 2,5‑disubstituted phospholane addressing these issues ...
Synthesis and ligand-based reduction chemistry of boron difluoride complexes with redox-active formazanate ligands M.-C. Chang ... From the themed collection: Non-Innocent Ligands The article was first published on 23 Dec 2014. Chem. Commun., 2015,51, 1553- ... From the themed collection: Non-Innocent Ligands The article was first published on 22 Jul 2014. Chem. Commun., 2014,50, 14290- ... From the themed collection: Non-Innocent Ligands The article was first published on 27 May 2014. Chem. Commun., 2014,50, 11440- ...
Ligand Efficacy.. In the functional assay, 5 of the 6 ligands behaved as inverse agonists (Fig. 5); the activity of the sixth ... The combination of potent new ligands that resemble known antagonists and structures dissimilar to previously explored ligands ... for kinase-like ligands, 0.9% for LGIC-like ligands, and an even smaller proportion that resembles biogenic molecules such as ... using ligand probe charges in an electrostatic potential calculated by DelPhi (13, 21, 22)], corrected for ligand desolvation ( ...
These chelating ligands form catalytically active complexes with Pd and Pt and can efficiently be utilized in the ... Only recently, have sp2-hybridized phosphorus compounds been utilized as ligands for transition metals in catalysis. The ... Even polysubstituted alkenes can be converted which is not possible using classical lambda3-sigma3-phosphane ligands. ... Our research is aimed at the synthesis on development of novel chelating ligands that exhibit low-coordinate trivalent ...
Dr James Firth, lead chemist on the project, said: "Our approach to the family of sparteine chiral ligands allows synthesis of ... Their route uses common feedstock chemicals to make these chiral ligands on an unprecedented scale, moving away from the ... Sparteine and the sparteine surrogate, developed in York in 2002, are chiral ligands with the potential to synthesise mirror- ... York chemists solve long-term supply issues of sparteine chiral ligands. Posted on 30 January 2018 ...
Overall, 800 ligand-target predictions of prospectively designed ligands were tested experimentally, of which 75% were ... Automated design of ligands to polypharmacological profiles.. Besnard J1, Ruda GF, Setola V, Abecassis K, Rodriguiz RM, Huang ... a) Closed loop of automated ligand design algorithm by multi-objective evolutionary optimisation. (b) Multi-objective ... Here we describe a new approach for the automated design of ligands against profiles of multiple drug targets. The method is ...
Novel compounds show high affinity for specific cocainereceptors in the brain, particularly dopamine transporter sites,and have the formula ##STR1## Wherein Y=CH.sub.2 R.sub.3, CO.sub.2R.sub.2 or ##STR2## R.sub.1 =hydrogen, C.sub.1-5 alkyl, R.sub.2=hydrogen, C.sub.1-6 alkyl, C.sub.3-8 cycloalkyl, C.sub.1-4 alkoxy,C.sub.1-6 alkynyl, halogen or amine, R.sub.3 =OH,
The ligand chosen for the reaction has showed outstanding results in a variety of cross-coupling transformations. Utilizing P(t ... Since the late 1990s several research groups have shown the versatility and efficiency of trialkyl phosphine ligands for a ... of ligand and 1.5 mol% of Pd2(dba)3, the reaction produced the desired biaryls with good to excellent yields (Table 1). It is ... Fu and coworkers explored the Hiyama transformation using one of their most versatile ligands, P(t-Bu)2Me.3 The Hiyama coupling ...
The invention relates to novel compounds which show highaffinity for cocaine receptors in the brain, particularly dopamineand serotonin transporter sites. The compounds may be used asimaging or pharmaceutical agents, in the diagnosis and treatment ofdrug addiction, depression, anorexia and neurodegenerativediseases.
... Dr E. Buxbaum EB15 at le.ac.uk Mon Mar 2 13:22:52 EST 1998 *Previous message: Algal Biliproteins ... Louis Hom wrote: , , Basic question: , Is there an activation energy associated with ligand binding? Yes, there is, and it is ...
Ligand Expo An RCSB PDB resource for searching, exploring, and downloading information and coordinates about the chemical ... GET as free ligands, exist in 10 entries. Examples include 1MWL, 1NJJ, 3TD1 ... An encyclopedia dedicated to a ligand oriented view that integrates different information about drug-likeness or binding ...
TA8 as free ligands, exist in 1 entries. Examples include 4A6R, Find related ligands: Stereoisomers Similar ligands Chemical ... Ligand Expo An RCSB PDB resource for searching, exploring, and downloading information and coordinates about the chemical ... An encyclopedia dedicated to a ligand oriented view that integrates different information about drug-likeness or binding ...
... and Welfare gave its approval to Ligand partner GlaxoSmithKlines ... San Diegos Ligand Pharmaceuticals (NASDAQ: LGND) says Japans ... San Diegos Ligand Pharmaceuticals (NASDAQ: ]) says Japans Ministry of Health, Labor, ... Ligand says eltrombopag is the first oral treatment that stimulates the production of blood platelets, considered essential to ... Ministry of Health, Labor, and Welfare gave its approval to Ligand partner GlaxoSmithKlines (NYSE: GSK) application for ...
  • Ligands whose orbitals interact only weakly with the metal cation's orbitals are called weak-field ligands. (britannica.com)
  • For transition metal ions with electron configurations d 0 through d 3 and d 8 through d 10 , only one configuration is possible, so the net spin of the electrons in the complex is the same for both strong-field and weak-field ligands. (britannica.com)
  • Ligands that produce a small Δ are called weak-field ligands and lie at the left end of the series. (davidson.edu)
  • Under the new accounting standard ASC 606, adopted at the start of this year, Ligand said that third-quarter 2018 royalties should be compared with fourth-quarter 2017 royalties due to the timing of revenue recognition. (nasdaq.com)
  • Ligand increased its guidance for 2018 for the second consecutive quarter. (nasdaq.com)
  • He showed, among other things, that the formulas of many cobalt(III) and chromium(III) compounds can be understood if the metal has six ligands in an octahedral geometry. (wikipedia.org)
  • The magnitude of Δ t is smaller than for Δ o , because in a tetrahedral complex only 4 ligands influence the d-orbitals, whereas in an octahedral complex the d-orbitals are influenced by 6 ligands. (wikipedia.org)
  • The orbital splitting between the two sets of orbitals ( t 2 g and e g ) is designated as the orbital ligand field parameter , δ o (where o stands for octahedral). (britannica.com)
  • Our research is aimed at the synthesis on development of novel chelating ligands that exhibit low-coordinate trivalent phosphorus moieties. (yorku.ca)
  • High-affinity binding of ligands to receptors is often physiologically important when some of the binding energy can be used to cause a conformational change in the receptor, resulting in altered behavior of an associated ion channel or enzyme . (wikipedia.org)
  • We show that DNA-based hairpin ligands, which undergo well-defined conformational changes upon binding of effector oligonucleotides, can be used to alter the bonding properties of the nanoparticles to which they are anchored. (sciencemag.org)
  • The conformational change in the ligands due to thisinteraction may explain the different selectivities observed inthe catalytic reaction. (diva-portal.org)
  • Ligand-in-duced conformational changes in r IucD were assessed by monitoring its CD spectra, DSC profile, and susceptibility to both endo- as well as exopeptidases. (umich.edu)
  • We have developed five ligands for PET imaging of metabotropic glutamate subgroup 5 receptors and investigated mGluR functions in animal models of different neurodegenerative disorders. (ingentaconnect.com)
  • We thus followed in a mouse model as well as in several clinical situations the variations in plasma Flt3 ligand concentration, after either homogeneous or heterogeneous irradiations. (irsn.fr)
  • The TmMe anion is a tridentate, tripodal ligand topologically similar to the more common Tp ligands, but the two classes of ligands differ in several ways. (wikipedia.org)
  • GET as free ligands, exist in 10 entries . (rcsb.org)
  • TA8 as free ligands, exist in 1 entries . (rcsb.org)
  • For sparteine, these were then recombined to generate the complexity required in the target ligand. (york.ac.uk)
  • c. relating the detectable signal to the presence of said target ligand in said fluid sample. (google.ca)
  • Their route uses common feedstock chemicals to make these chiral ligands on an unprecedented scale, moving away from the precarious use of naturally occurring compounds, and hence allowing supply issues to be addressed. (york.ac.uk)
  • Dr James Firth, lead chemist on the project, said: "Our approach to the family of sparteine chiral ligands allows synthesis of either mirror-image form on a gram-scale for the first time. (york.ac.uk)
  • Privileged Chiral Ligands and Catalysts Qi-Lin Zhou 2011 H-U. Blaser, W. Brieden, B. Pugin, F. Spindler, M. Studer and A. Togni, Top. (wikipedia.org)
  • Although there are many known ligands for main olfactory receptor neurons, our understanding of the natural ligands for VSNs is woefully incomplete. (jneurosci.org)
  • Myoglobin (blue) with its ligand heme (orange) bound. (wikipedia.org)
  • Metals and metalloids are bound to ligands in virtually all circumstances, although gaseous "naked" metal ions can be generated in a high vacuum. (wikipedia.org)
  • designed a series of gold colloids with DNA ligands that reversibly bound to or released neighboring particles via DNA strands that opened or closed hairpin loops. (sciencemag.org)
  • Soluble Fas ligand is generated by cleaving membrane-bound FasL at a conserved cleavage site by the external serine matrix metalloproteinase MMP-7. (bionity.com)
  • Metals bound to so-called triply bonded carbyne , imide , nitride ( nitrido ), and oxide ( oxo ) ligands are generally assigned to high oxidation states with low d electron counts. (wikipedia.org)
  • In the case of the ligand bound with iron, a two-step process emerges that places the hole on the iron, again at rates much faster than band gap recombination. (osti.gov)
  • Ligands are classified in many ways, including: charge, size (bulk), the identity of the coordinating atom(s), and the number of electrons donated to the metal ( denticity or hapticity ). (wikipedia.org)
  • This is because the ligand and central metal are bonded to one another, and the ligand is providing both electrons to the bond (lone pair of electrons) instead of the metal and ligand each providing one electron. (wikipedia.org)
  • Ligands should have minimum one lone pair of electron, where it donates two electrons to the metal. (bartleby.com)
  • Monodentate ligand is ligands which donate only one pair of electrons to form bond with metal. (bartleby.com)
  • The essential feature of a coordination compound is the donation of a pair of electrons by the ligand to form a coordinate covalent bond with the metal. (davidson.edu)
  • Ligand did not receive any Promacta royalties in the third quarter of 2019 and will not receive any Promacta royalties going forward. (benzinga.com)
  • As of September 30, 2019, Ligand had cash, cash equivalents and short-term investments of $1.1 billion. (benzinga.com)
  • ligands on cells for specific homing receptors on lymphocytes. (drugs.com)
  • Moreover, we showed that T lymphocytes are not the main regulator of plasma Flt3 ligand concentration as previously suggested, and that other cell types, possibly including bone marrow stromal cells, might be strongly implicated. (irsn.fr)
  • Excluding items, Ligand Pharmaceuticals Inc reported adjusted earnings of $13.89 million or $0.68 per share for the period. (rttnews.com)
  • With Icagen in line to generate income from services and license and milestone fees in the near term, Ligand thinks the deal will be immediately accretive to revenues and earnings. (fiercebiotech.com)
  • Sometimes reaction can be very slow, and even if the stability constants dictate that one ligand should be replaced with the other, it takes so long complex with lower stability constant may behave as a more stable one. (physicsforums.com)
  • As of December 31, 2012, Ligand had cash, cash equivalents, short-term investments and restricted investments of $15.1 million and accounts receivable of $4.6 million. (thestreet.com)
  • Ligand primarily earned royalties on sales of Novartis' NVS Promacta, Amgen's AMGN Kyprolis and Spectrum Pharmaceuticals' SPPI Evomela, which were developed using Ligand's Captisol technology. (nasdaq.com)
  • Ligand needs Promacta approved to juice up its revenue. (fool.com)
  • We are very pleased with the continued revenue growth of Promacta ® , partnered with GlaxoSmithKline, and believe the approval of Onyx's drug Kyprolis ® in 2012 is a significant event for Ligand and our Captisol ® business. (thestreet.com)
  • In this review we evaluate our data in comparison to the theoretical and experimental aspects of developing selective and sensitive imaging ligands for in vivo imaging. (ingentaconnect.com)
  • However, there are also organic species that can chelate a metal, providing some of its ligands. (everything2.com)
  • A particularly fruitful synthetic avenue has been the deployment of multi-dentate ancillary ligands bearing one or more substituents containing additional functionality, capable of weakly binding to the metal. (mendeley.com)
  • Coordination supramolecules (CSs), constructed by assembly of metal ions/clusters (referred as nodes) and organic bridging ligands (referred as linkers), are a class of inorganic-organic hybrid materials. (rsc.org)
  • The nature of metal-ligand bonding can range from covalent to ionic . (wikipedia.org)
  • Furthermore, the metal-ligand bond order can range from one to three. (wikipedia.org)
  • This ordering of ligands is almost invariable for all metal ions and is called spectrochemical series . (wikipedia.org)
  • Polydentate ligand forms two or more coordination bond with metal ions to form a complex. (bartleby.com)
  • The six ligand donor orbitals are grouped into two sets, one of which has appropriate symmetry for interacting with the metal d z 2 orbital and the other with appropriate symmetry for interacting with the metal d x 2 -y 2 orbital. (davidson.edu)
  • The Lewis acid-base reaction between the metal and the ligand results in a set of low energy, fully occupied (because the original ligand donor orbitals were fully occupied) σ bonding orbitals that are primarily localized on the ligand and a set of high energy σ* orbitals that are primarily localized on the metal. (davidson.edu)
  • Three of the metal orbitals (d xy , d xz , and d yz ) do not interact with the ligand orbitals and remain as nonbonding orbitals completely centered on the metal. (davidson.edu)
  • The occupied ligand orbitals are lower in energy than the metal orbitals. (davidson.edu)
  • As a cautionary note, the classification of a metal ligand bond as being "multiple" bond order is ambiguous and even arbitrary because bond order is a formalism. (wikipedia.org)
  • The term 'metal ligand multiple bond" is often reserved for ligands of the type CR n and NR n (n = 0, 1, 2) and OR n (n = 0, 1) where R is H or an organic substituent, or pseudohalide. (wikipedia.org)
  • A ligand described in ionic terms can bond to a metal through however many lone pairs it has available. (wikipedia.org)
  • The dithiocarbamate$-$bipyridine ligand system facilitates hole transfer through energetic overlap at the inorganic$-$organic interface and conjugation through the organic ligand to a chelated metal center. (osti.gov)
  • These ligands are highly active for enantioselective hydroformylation and enantioselective allylic alkylation reactions. (sigmaaldrich.com)
  • Figure 2: Xyliphos ligand The ligands are also used in non-enantioselective reactions. (wikipedia.org)
  • Coupling with Grignards and Negishi coupling reactions A variety of Josiphos ligands are commercially available, under licence from Solvias. (wikipedia.org)
  • Are ALL ligand exchange reactions reversible? (physicsforums.com)
  • In biochemistry and pharmacology , a ligand is a substance that forms a complex with a biomolecule to serve a biological purpose. (wikipedia.org)
  • Measurably irreversible covalent bonding between a ligand and target molecule is atypical in biological systems. (wikipedia.org)
  • Recent results indicated that the plasma Flt3 ligand concentration was increased in patients suffering from either acquired or induced aplasia, suggesting that Flt3 ligand might be useful as a biological indicator of bone marrow status. (irsn.fr)
  • Nevertheless, the clinical use of Flt3 ligand as a biological indicator of bone marrow damage require the knowledge of the mechanisms regulating the variations in plasma Flt3 ligand concentration. (irsn.fr)
  • To examine whether CDCA mediates its transcriptional effects through an orphan member of the steroid-retinoid-thyroid hormone receptor family ( 4 ), we used a chimeric receptor system in which the putative ligand-binding domain (LBD) of the human orphan receptor is fused to the DNA binding domain of the yeast transcription factor GAL4 ( 5 ). (sciencemag.org)
  • Ligand is a BioPharma company with a business model that is based upon the concept of developing or acquiring royalty revenue generating assets and coupling them to an efficiently lean corporate cost structure. (annualreports.com)
  • US biopharma Ligand Pharmaceuticals has announced its intention to buy UK biotech Vernalis for approximately $43 million. (bioportfolio.com)