Aspartic Acid Endopeptidases: A sub-subclass of endopeptidases that depend on an ASPARTIC ACID residue for their activity.Aspartic Acid: One of the non-essential amino acids commonly occurring in the L-form. It is found in animals and plants, especially in sugar cane and sugar beets. It may be a neurotransmitter.Endopeptidases: A subclass of PEPTIDE HYDROLASES that catalyze the internal cleavage of PEPTIDES or PROTEINS.Neprilysin: Enzyme that is a major constituent of kidney brush-border membranes and is also present to a lesser degree in the brain and other tissues. It preferentially catalyzes cleavage at the amino group of hydrophobic residues of the B-chain of insulin as well as opioid peptides and other biologically active peptides. The enzyme is inhibited primarily by EDTA, phosphoramidon, and thiorphan and is reactivated by zinc. Neprilysin is identical to common acute lymphoblastic leukemia antigen (CALLA Antigen), an important marker in the diagnosis of human acute lymphocytic leukemia. There is no relationship with CALLA PLANT.Aspartic Acid Proteases: A subclass of peptide hydrolases that depend on an ASPARTIC ACID residue for their activity.Serine Endopeptidases: Any member of the group of ENDOPEPTIDASES containing at the active site a serine residue involved in catalysis.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.Thiorphan: A potent inhibitor of membrane metalloendopeptidase (ENKEPHALINASE). Thiorphan potentiates morphine-induced ANALGESIA and attenuates naloxone-precipitated withdrawal symptoms.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.Protease Inhibitors: Compounds which inhibit or antagonize biosynthesis or actions of proteases (ENDOPEPTIDASES).PHEX Phosphate Regulating Neutral Endopeptidase: A membrane-bound metalloendopeptidase that may play a role in the degradation or activation of a variety of PEPTIDE HORMONES and INTERCELLULAR SIGNALING PEPTIDES AND PROTEINS. Genetic mutations that result in loss of function of this protein are a cause of HYPOPHOSPHATEMIC RICKETS, X-LINKED DOMINANT.Cysteine Endopeptidases: ENDOPEPTIDASES which have a cysteine involved in the catalytic process. This group of enzymes is inactivated by CYSTEINE PROTEINASE INHIBITORS such as CYSTATINS and SULFHYDRYL REAGENTS.Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (-COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins.Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.Mutagenesis, Site-Directed: Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.Asparagine: A non-essential amino acid that is involved in the metabolic control of cell functions in nerve and brain tissue. It is biosynthesized from ASPARTIC ACID and AMMONIA by asparagine synthetase. (From Concise Encyclopedia Biochemistry and Molecular Biology, 3rd ed)Metalloendopeptidases: ENDOPEPTIDASES which use a metal such as ZINC in the catalytic mechanism.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Kinetics: The rate dynamics in chemical or physical systems.Glycopeptides: Proteins which contain carbohydrate groups attached covalently to the polypeptide chain. The protein moiety is the predominant group with the carbohydrate making up only a small percentage of the total weight.Pepstatins: N-acylated oligopeptides isolated from culture filtrates of Actinomycetes, which act specifically to inhibit acid proteases such as pepsin and renin.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.Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water.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.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Oligopeptides: Peptides composed of between two and twelve amino acids.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.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)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.Glutamates: Derivatives of GLUTAMIC ACID. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain the 2-aminopentanedioic acid structure.Peptide Fragments: Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.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.Models, Molecular: Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.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.Isoaspartic Acid: An ASPARTIC ACID residue in polypeptide chains that is linked at the beta-carboxyl group instead of at the normal, alpha-carboxyl group, polypeptide linkage. It is a result of the spontaneous decomposition of aspartic acid or ASPARAGINE residues.Cathepsin E: An aspartic endopeptidase that is similar in structure to CATHEPSIN D. It is found primarily in the cells of the immune system where it may play a role in processing of CELL SURFACE ANTIGENS.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).Chromatography, High Pressure Liquid: Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed.Histidine: An essential amino acid that is required for the production of HISTAMINE.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.Neurotensin: A biologically active tridecapeptide isolated from the hypothalamus. It has been shown to induce hypotension in the rat, to stimulate contraction of guinea pig ileum and rat uterus, and to cause relaxation of rat duodenum. There is also evidence that it acts as both a peripheral and a central nervous system neurotransmitter.Alanine: A non-essential amino acid that occurs in high levels in its free state in plasma. It is produced from pyruvate by transamination. It is involved in sugar and acid metabolism, increases IMMUNITY, and provides energy for muscle tissue, BRAIN, and the CENTRAL NERVOUS SYSTEM.Lysostaphin: A 25-kDa peptidase produced by Staphylococcus simulans which cleaves a glycine-glcyine bond unique to an inter-peptide cross-bridge of the STAPHYLOCOCCUS AUREUS cell wall. EC 3.4.24.75.Serine Proteinase Inhibitors: Exogenous or endogenous compounds which inhibit SERINE ENDOPEPTIDASES.Pepsin A: Formed from pig pepsinogen by cleavage of one peptide bond. The enzyme is a single polypeptide chain and is inhibited by methyl 2-diaazoacetamidohexanoate. It cleaves peptides preferentially at the carbonyl linkages of phenylalanine or leucine and acts as the principal digestive enzyme of gastric juice.Catalysis: The facilitation of a chemical reaction by material (catalyst) that is not consumed by the reaction.Electrophoresis, Polyacrylamide Gel: Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.Cathepsin D: An intracellular proteinase found in a variety of tissue. It has specificity similar to but narrower than that of pepsin A. The enzyme is involved in catabolism of cartilage and connective tissue. EC 3.4.23.5. (Formerly EC 3.4.4.23).Glycine: A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter.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.Dipeptides: Peptides composed of two amino acid units.Serine: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from GLYCINE or THREONINE. It is involved in the biosynthesis of PURINES; PYRIMIDINES; and other amino acids.Molecular Weight: The sum of the weight of all the atoms in a molecule.Peptide Hydrolases: Hydrolases that specifically cleave the peptide bonds found in PROTEINS and PEPTIDES. Examples of sub-subclasses for this group include EXOPEPTIDASES and ENDOPEPTIDASES.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.Catalytic Domain: The region of an enzyme that interacts with its substrate to cause the enzymatic reaction.Carboxypeptidases: Enzymes that act at a free C-terminus of a polypeptide to liberate a single amino acid residue.Protein Processing, Post-Translational: Any of various enzymatically catalyzed post-translational modifications of PEPTIDES or PROTEINS in the cell of origin. These modifications include carboxylation; HYDROXYLATION; ACETYLATION; PHOSPHORYLATION; METHYLATION; GLYCOSYLATION; ubiquitination; oxidation; proteolysis; and crosslinking and result in changes in molecular weight and electrophoretic motility.Trypsin: A serine endopeptidase that is formed from TRYPSINOGEN in the pancreas. It is converted into its active form by ENTEROPEPTIDASE in the small intestine. It catalyzes hydrolysis of the carboxyl group of either arginine or lysine. EC 3.4.21.4.Atrial Natriuretic Factor: A potent natriuretic and vasodilatory peptide or mixture of different-sized low molecular weight PEPTIDES derived from a common precursor and secreted mainly by the HEART ATRIUM. All these peptides share a sequence of about 20 AMINO ACIDS.Point Mutation: A mutation caused by the substitution of one nucleotide for another. This results in the DNA molecule having a change in a single base pair.Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid is the most common excitatory neurotransmitter in the CENTRAL NERVOUS SYSTEM.Chromatography, Gel: Chromatography on non-ionic gels without regard to the mechanism of solute discrimination.Cell Line: Established cell cultures that have the potential to propagate indefinitely.ThiazepinesProtein 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.Aspartate-tRNA Ligase: An enzyme that activates aspartic acid with its specific transfer RNA. EC 6.1.1.12.Protein PrecursorsThermolysin: A thermostable extracellular metalloendopeptidase containing four calcium ions. (Enzyme Nomenclature, 1992) 3.4.24.27.Proline: A non-essential amino acid that is synthesized from GLUTAMIC ACID. It is an essential component of COLLAGEN and is important for proper functioning of joints and tendons.Bacterial Proteins: Proteins found in any species of bacterium.Enzyme Stability: The extent to which an enzyme retains its structural conformation or its activity when subjected to storage, isolation, and purification or various other physical or chemical manipulations, including proteolytic enzymes and heat.Cathepsin B: A lysosomal cysteine proteinase with a specificity similar to that of PAPAIN. The enzyme is present in a variety of tissues and is important in many physiological and pathological processes. In pathology, cathepsin B has been found to be involved in DEMYELINATION; EMPHYSEMA; RHEUMATOID ARTHRITIS, and NEOPLASM INVASIVENESS.Enzyme Precursors: Physiologically inactive substances that can be converted to active enzymes.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.PeptidoglycanChromatography, Ion Exchange: Separation technique in which the stationary phase consists of ion exchange resins. The resins contain loosely held small ions that easily exchange places with other small ions of like charge present in solutions washed over the resins.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.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.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.Carbohydrates: The largest class of organic compounds, including STARCH; GLYCOGEN; CELLULOSE; POLYSACCHARIDES; and simple MONOSACCHARIDES. Carbohydrates are composed of carbon, hydrogen, and oxygen in a ratio of Cn(H2O)n.Conserved Sequence: A sequence of amino acids in a polypeptide or of nucleotides in DNA or RNA that is similar across multiple species. A known set of conserved sequences is represented by a CONSENSUS SEQUENCE. AMINO ACID MOTIFS are often composed of conserved sequences.Cathepsins: A group of lysosomal proteinases or endopeptidases found in aqueous extracts of a variety of animal tissues. They function optimally within an acidic pH range. The cathepsins occur as a variety of enzyme subtypes including SERINE PROTEASES; ASPARTIC PROTEINASES; and CYSTEINE PROTEASES.Aminopeptidases: A subclass of EXOPEPTIDASES that act on the free N terminus end of a polypeptide liberating a single amino acid residue. EC 3.4.11.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.Plasmids: Extrachromosomal, usually CIRCULAR DNA molecules that are self-replicating and transferable from one organism to another. They are found in a variety of bacterial, archaeal, fungal, algal, and plant species. They are used in GENETIC ENGINEERING as CLONING VECTORS.Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of PAIN, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses.Chromatography: Techniques used to separate mixtures of substances based on differences in the relative affinities of the substances for mobile and stationary phases. A mobile phase (fluid or gas) passes through a column containing a stationary phase of porous solid or liquid coated on a solid support. Usage is both analytical for small amounts and preparative for bulk amounts.Threonine: An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins.Crystallography, X-Ray: The study of crystal structure using X-RAY DIFFRACTION techniques. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)Exopeptidases: A sub-class of PEPTIDE HYDROLASES that act only near the ends of polypeptide chains.Enkephalin, Leucine: One of the endogenous pentapeptides with morphine-like activity. It differs from MET-ENKEPHALIN in the LEUCINE at position 5. Its first four amino acid sequence is identical to the tetrapeptide sequence at the N-terminal of BETA-ENDORPHIN.Kidney: Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.Bradykinin: A nonapeptide messenger that is enzymatically produced from KALLIDIN in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from MAST CELLS during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter.Hypophosphatemia: A condition of an abnormally low level of PHOSPHATES in the blood.Botulinum Toxins, Type A: A serotype of botulinum toxins that has specificity for cleavage of SYNAPTOSOMAL-ASSOCIATED PROTEIN 25.Aspartate-Semialdehyde Dehydrogenase: An enzyme that catalyzes the conversion of L-aspartate 4-semialdehyde, orthophosphate, and NADP+ to yield L-4-aspartyl phosphate and NADPH. EC 1.2.1.11.Cell Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.Indans: Aryl CYCLOPENTANES that are a reduced (protonated) form of INDENES.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.Flavobacterium: A genus of gram-negative, aerobic, rod-shaped bacteria widely distributed in SOIL and WATER. Its organisms are also found in raw meats, MILK and other FOOD, hospital environments, and human clinical specimens. Some species are pathogenic in humans.Bacillus: A genus of BACILLACEAE that are spore-forming, rod-shaped cells. Most species are saprophytic soil forms with only a few species being pathogenic.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)Molecular 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.Arginine: An essential amino acid that is physiologically active in the L-form.Chemistry: A basic science concerned with the composition, structure, and properties of matter; and the reactions that occur between substances and the associated energy exchange.Chemical Phenomena: The composition, conformation, and properties of atoms and molecules, and their reaction and interaction processes.Forensic Sciences: Disciplines that apply sciences to law. Forensic sciences include a wide range of disciplines, such as FORENSIC TOXICOLOGY; FORENSIC ANTHROPOLOGY; FORENSIC MEDICINE; FORENSIC DENTISTRY; and others.Swine: Any of various animals that constitute the family Suidae and comprise stout-bodied, short-legged omnivorous mammals with thick skin, usually covered with coarse bristles, a rather long mobile snout, and small tail. Included are the genera Babyrousa, Phacochoerus (wart hogs), and Sus, the latter containing the domestic pig (see SUS SCROFA).Sequence Homology, Nucleic Acid: The sequential correspondence of nucleotides in one nucleic acid molecule with those of another nucleic acid molecule. Sequence homology is an indication of the genetic relatedness of different organisms and gene function.ATP-Dependent Endopeptidases: Endoproteases that contain proteolytic core domains and ATPase-containing regulatory domains.Castor Bean: Common name for Ricinus communis, a species in the family EUPHORBIACEAE. It is the source of CASTOR OIL.Keratin-2: A type II keratin found expressed in the upper spinous layer of epidermal KERATINOCYTES. Mutations in genes that encode keratin-2A have been associated with ICHTHYOSIS BULLOSA OF SIEMENS.Plant Proteins: Proteins found in plants (flowers, herbs, shrubs, trees, etc.). The concept does not include proteins found in vegetables for which VEGETABLE PROTEINS is available.Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.Chromatography, Paper: An analytical technique for resolution of a chemical mixture into its component compounds. Compounds are separated on an adsorbent paper (stationary phase) by their varied degree of solubility/mobility in the eluting solvent (mobile phase).Lysine: An essential amino acid. It is often added to animal feed.Zinc: A metallic element of atomic number 30 and atomic weight 65.38. It is a necessary trace element in the diet, forming an essential part of many enzymes, and playing an important role in protein synthesis and in cell division. Zinc deficiency is associated with ANEMIA, short stature, HYPOGONADISM, impaired WOUND HEALING, and geophagia. It is known by the symbol Zn.Cysteine: A thiol-containing non-essential amino acid that is oxidized to form CYSTINE.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.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)Mass Spectrometry: An analytical method used in determining the identity of a chemical based on its mass using mass analyzers/mass spectrometers.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.Carboxypeptidases A: Carboxypeptidases that are primarily found the DIGESTIVE SYSTEM that catalyze the release of C-terminal amino acids. Carboxypeptidases A have little or no activity for hydrolysis of C-terminal ASPARTIC ACID; GLUTAMIC ACID; ARGININE; LYSINE; or PROLINE. This enzyme requires ZINC as a cofactor and was formerly listed as EC 3.4.2.1 and EC 3.4.12.2.Papain: A proteolytic enzyme obtained from Carica papaya. It is also the name used for a purified mixture of papain and CHYMOPAPAIN that is used as a topical enzymatic debriding agent. EC 3.4.22.2.Rabbits: The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.Mutation, Missense: A mutation in which a codon is mutated to one directing the incorporation of a different amino acid. This substitution may result in an inactive or unstable product. (From A Dictionary of Genetics, King & Stansfield, 5th ed)Propionates: Derivatives of propionic acid. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain the carboxyethane structure.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.Chymotrypsin: A serine endopeptidase secreted by the pancreas as its zymogen, CHYMOTRYPSINOGEN and carried in the pancreatic juice to the duodenum where it is activated by TRYPSIN. It selectively cleaves aromatic amino acids on the carboxyl side.Subtilisins: A family of SERINE ENDOPEPTIDASES isolated from Bacillus subtilis. EC 3.4.21.-2S Albumins, Plant: A major class of water-soluble seed storage proteins. Many proteins from this class are major PLANT ALLERGENS.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).)Peptide Mapping: Analysis of PEPTIDES that are generated from the digestion or fragmentation of a protein or mixture of PROTEINS, by ELECTROPHORESIS; CHROMATOGRAPHY; or MASS SPECTROMETRY. The resulting peptide fingerprints are analyzed for a variety of purposes including the identification of the proteins in a sample, GENETIC POLYMORPHISMS, patterns of gene expression, and patterns diagnostic for diseases.Radiometric Dating: Techniques used to determine the age of materials, based on the content and half-lives of the RADIOACTIVE ISOTOPES they contain.Cyanogen Bromide: Cyanogen bromide (CNBr). A compound used in molecular biology to digest some proteins and as a coupling reagent for phosphoroamidate or pyrophosphate internucleotide bonds in DNA duplexes.Leucine: An essential branched-chain amino acid important for hemoglobin formation.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.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).Macromolecular Substances: Compounds and molecular complexes that consist of very large numbers of atoms and are generally over 500 kDa in size. In biological systems macromolecular substances usually can be visualized using ELECTRON MICROSCOPY and are distinguished from ORGANELLES by the lack of a membrane structure.Restriction Mapping: Use of restriction endonucleases to analyze and generate a physical map of genomes, genes, or other segments of DNA.Homoserine Dehydrogenase: An enzyme that catalyzes the reduction of aspartic beta-semialdehyde to homoserine, which is the branch point in biosynthesis of methionine, lysine, threonine and leucine from aspartic acid. EC 1.1.1.3.Familial Hypophosphatemic Rickets: A hereditary disorder characterized by HYPOPHOSPHATEMIA; RICKETS; OSTEOMALACIA; renal defects in phosphate reabsorption and vitamin D metabolism; and growth retardation. Autosomal and X-linked dominant and recessive variants have been reported.Hydrogen Bonding: A low-energy attractive force between hydrogen and another element. It plays a major role in determining the properties of water, proteins, and other compounds.Angiotensin-Converting Enzyme Inhibitors: A class of drugs whose main indications are the treatment of hypertension and heart failure. They exert their hemodynamic effect mainly by inhibiting the renin-angiotensin system. They also modulate sympathetic nervous system activity and increase prostaglandin synthesis. They cause mainly vasodilation and mild natriuresis without affecting heart rate and contractility.Chymosin: The predominant milk-clotting enzyme from the true stomach or abomasum of the suckling calf. It is secreted as an inactive precursor called prorennin and converted in the acid environment of the stomach to the active enzyme. EC 3.4.23.4.Cell Wall: The outermost layer of a cell in most PLANTS; BACTERIA; FUNGI; and ALGAE. The cell wall is usually a rigid structure that lies external to the CELL MEMBRANE, and provides a protective barrier against physical or chemical agents.Mutagenesis: Process of generating a genetic MUTATION. It may occur spontaneously or be induced by MUTAGENS.Peptidyl-Dipeptidase A: A peptidyl-dipeptidase that catalyzes the release of a C-terminal dipeptide, -Xaa-*-Xbb-Xcc, when neither Xaa nor Xbb is Pro. It is a Cl(-)-dependent, zinc glycoprotein that is generally membrane-bound and active at neutral pH. It may also have endopeptidase activity on some substrates. (From Enzyme Nomenclature, 1992) EC 3.4.15.1.Chromatography, DEAE-Cellulose: A type of ion exchange chromatography using diethylaminoethyl cellulose (DEAE-CELLULOSE) as a positively charged resin. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)Ketosteroids: Steroid derivatives formed by oxidation of a methyl group on the side chain or a methylene group in the ring skeleton to form a ketone.Temperature: The property of objects that determines the direction of heat flow when they are placed in direct thermal contact. The temperature is the energy of microscopic motions (vibrational and translational) of the particles of atoms.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.Phenylalanine: An essential aromatic amino acid that is a precursor of MELANIN; DOPAMINE; noradrenalin (NOREPINEPHRINE), and THYROXINE.Isoflurophate: A di-isopropyl-fluorophosphate which is an irreversible cholinesterase inhibitor used to investigate the NERVOUS SYSTEM.Sequence Analysis, DNA: A multistage process that includes cloning, physical mapping, subcloning, determination of the DNA SEQUENCE, and information analysis.Isoelectric Focusing: Electrophoresis in which a pH gradient is established in a gel medium and proteins migrate until they reach the site (or focus) at which the pH is equal to their isoelectric point.Pepsinogens: Proenzymes secreted by chief cells, mucous neck cells, and pyloric gland cells, which are converted into pepsin in the presence of gastric acid or pepsin itself. (Dorland, 28th ed) In humans there are 2 related pepsinogen systems: PEPSINOGEN A (formerly pepsinogen I or pepsinogen) and PEPSINOGEN C (formerly pepsinogen II or progastricsin). Pepsinogen B is the name of a pepsinogen from pigs.Leucyl Aminopeptidase: A zinc containing enzyme of the hydrolase class that catalyzes the removal of the N-terminal amino acid from most L-peptides, particularly those with N-terminal leucine residues but not those with N-terminal lysine or arginine residues. This occurs in tissue cell cytosol, with high activity in the duodenum, liver, and kidney. The activity of this enzyme is commonly assayed using a leucine arylamide chromogenic substrate such as leucyl beta-naphthylamide.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.Oligodeoxyribonucleotides: A group of deoxyribonucleotides (up to 12) in which the phosphate residues of each deoxyribonucleotide act as bridges in forming diester linkages between the deoxyribose moieties.Kinins: A generic term used to describe a group of polypeptides with related chemical structures and pharmacological properties that are widely distributed in nature. These peptides are AUTACOIDS that act locally to produce pain, vasodilatation, increased vascular permeability, and the synthesis of prostaglandins. Thus, they comprise a subset of the large number of mediators that contribute to the inflammatory response. (From Goodman and Gilman's The Pharmacologic Basis of Therapeutics, 8th ed, p588)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.Electrophoresis: An electrochemical process in which macromolecules or colloidal particles with a net electric charge migrate in a solution under the influence of an electric current.Codon: A set of three nucleotides in a protein coding sequence that specifies individual amino acids or a termination signal (CODON, TERMINATOR). Most codons are universal, but some organisms do not produce the transfer RNAs (RNA, TRANSFER) complementary to all codons. These codons are referred to as unassigned codons (CODONS, NONSENSE).Aminocaproates: Amino derivatives of caproic acid. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain the amino caproic acid structure.Seed Storage Proteins: One or more types of plant seed proteins providing the large amounts of AMINO ACIDS utilized in GERMINATION and SEEDLING growth. As seeds are the major food source from AGRICULTURAL CROPS, seed storage proteins are a major source of DIETARY PROTEINS.Neuraminic AcidsHydroxylamines: Organic compounds that contain the (-NH2OH) radical.Isoelectric Point: The pH in solutions of proteins and related compounds at which the dipolar ions are at a maximum.Cathepsin C: A papain-like cysteine protease that has specificity for amino terminal dipeptides. The enzyme plays a role in the activation of several pro-inflammatory serine proteases by removal of their aminoterminal inhibitory dipeptides. Genetic mutations that cause loss of cathepsin C activity in humans are associated with PAPILLON-LEFEVRE DISEASE.Saccharomyces cerevisiae: A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as "baker's" or "brewer's" yeast. The dried form is used as a dietary supplement.Muramidase: A basic enzyme that is present in saliva, tears, egg white, and many animal fluids. It functions as an antibacterial agent. The enzyme catalyzes the hydrolysis of 1,4-beta-linkages between N-acetylmuramic acid and N-acetyl-D-glucosamine residues in peptidoglycan and between N-acetyl-D-glucosamine residues in chitodextrin. EC 3.2.1.17.

Stabilization from autoproteolysis and kinetic characterization of the human T-cell leukemia virus type 1 proteinase. (1/2015)

We have developed a system for expression and purification of wild-type human T-cell leukemia virus type 1 (HTLV-1) proteinase to attain sufficient quantities for structural, kinetic, and biophysical investigations. However, similar to the human immunodeficiency virus type 1 (HIV-1) proteinase, HTLV-1 proteinase also undergoes autoproteolysis rapidly upon renaturation to produce two products. The site of this autoproteolytic cleavage was mapped, and a resistant HTLV-1 proteinase construct (L40I) as well as another construct, wherein the two cysteine residues were exchanged to alanines, were expressed and purified. Oligopeptide substrates representing the naturally occurring cleavage sites in HTLV-1 were good substrates of the HTLV-1 proteinase. The kinetic parameters kcat and Km were nearly identical for all the three enzymes. Although three of four peptides representing HTLV-1 proteinase cleavage sites were fairly good substrates of HIV-1 proteinase, only two of nine peptides representing HIV-1 proteinase cleavage sites were hydrolyzed by the HTLV-1 proteinase, suggesting substantial differences in the specificity of the two enzymes. The large difference in the specificity of the two enzymes was also demonstrated by inhibition studies. Of the several inhibitors of HIV-1 or other retroviral proteinases that were tested on HTLV-1 proteinase, only two inhibit the enzyme with a Ki lower than 100 nM.  (+info)

Fus3p and Kss1p control G1 arrest in Saccharomyces cerevisiae through a balance of distinct arrest and proliferative functions that operate in parallel with Far1p. (2/2015)

In Saccharomyces cerevisiae, mating pheromones activate two MAP kinases (MAPKs), Fus3p and Kss1p, to induce G1 arrest prior to mating. Fus3p is known to promote G1 arrest by activating Far1p, which inhibits three Clnp/Cdc28p kinases. To analyze the contribution of Fus3p and Kss1p to G1 arrest that is independent of Far1p, we constructed far1 CLN strains that undergo G1 arrest from increased activation of the mating MAP kinase pathway. We find that Fus3p and Kss1p both control G1 arrest through multiple functions that operate in parallel with Far1p. Fus3p and Kss1p together promote G1 arrest by repressing transcription of G1/S cyclin genes (CLN1, CLN2, CLB5) by a mechanism that blocks their activation by Cln3p/Cdc28p kinase. In addition, Fus3p and Kss1p counteract G1 arrest through overlapping and distinct functions. Fus3p and Kss1p together increase the expression of CLN3 and PCL2 genes that promote budding, and Kss1p inhibits the MAP kinase cascade. Strikingly, Fus3p promotes proliferation by a novel function that is not linked to reduced Ste12p activity or increased levels of Cln2p/Cdc28p kinase. Genetic analysis suggests that Fus3p promotes proliferation through activation of Mcm1p transcription factor that upregulates numerous genes in G1 phase. Thus, Fus3p and Kss1p control G1 arrest through a balance of arrest functions that inhibit the Cdc28p machinery and proliferative functions that bypass this inhibition.  (+info)

Pregnancy detection and the effects of age, body weight, and previous reproductive performance on pregnancy status and weaning rates of farmed fallow deer (Dama dama). (3/2015)

Fallow does (n = 502) of different ages (mature, 2-yr-old, and yearling) were maintained with bucks for a 60-d breeding season to determine whether previous reproductive performance and changes in BW affect doe pregnancy rates and to compare the effectiveness of ultrasonography and serum pregnancy-specific protein B (PSPB) for the detection of pregnancy in fallow does. Ultrasonography was performed, blood samples collected, and BW recorded at buck removal (d 0) and at 30 and 90 d after buck removal. Lactational status (lactating = WET; nonlactating = DRY) were determined from farm records taken at weaning prior to each breeding season (autumn 1990 through autumn 1994). Ultrasonography and PSPB for determining pregnancy were in agreement 93% of the time. Overall pregnancy rates did not differ (P>.10) relative to age of the doe; the combined pregnancy rate was 92%. We also determined that 82.9% of does conceived early in the breeding season and that the incidence of embryonal-fetal mortality during the first 90 d after buck removal was 2.8%. In general, mature and 2-yr-old DRY does were heavier and had lower pregnancy rates than WET does. The overall weaning rate for all does was 77.9%. Loss in the number of fawns from pregnancy detection to weaning was equivalent to 14.8% for mature does, 24.7% for 2 yr old does, and 42.5% for yearling does. These data indicate that even though pregnancy rates were relatively high, further study is needed to determine the causes associated with subsequent fawn losses, particularly among yearling does. As a production tool, lactational WET/ DRY status testing was found to be an acceptable means for determining the reproductive potential of individual does within the herd. In addition, serum PSPB may be used in place of ultrasonography for pregnancy diagnosis in fallow deer as early as d 30 after buck removal.  (+info)

Endothelin-1 and its mRNA in the wall layers of human arteries ex vivo. (4/2015)

BACKGROUND: The participation of endothelin-1 (ET-1) in the control of vascular tone in humans has been questioned, on the basis of the finding of subthreshold immunoreactive (ir) ET-1 plasma levels. However, because most ET-1 is secreted abluminally, it might attain a higher concentration in the tunica media than in plasma. Furthermore, evidence indicates that vascular smooth muscle cells (VSMCs) can synthesize ET-1 on stimulation in vitro. We therefore looked for irET-1 in the different layers of the wall of human arteries, including renal, gastric, and internal thoracic artery wall, obtained ex vivo from consenting patients with coronary artery disease and/or high blood pressure undergoing surgery, as well as from young organ donors. METHODS AND RESULTS: We performed immunohistochemistry with specific anti-ET-1 and anti-vWF antibodies followed by detection with an avidin-biotin complex ultrasensitive kit. The presence of preproET-1 and human endothelin-converting enzyme-1 (hECE-1) mRNA was also investigated by reverse transcription-polymerase chain reaction in homogenates of vessel wall, including preparations deprived of both endothelium and adventitia, and in isolated VSMCs. We detected irET-1 in the endothelium of all arteries and in the tunica media of internal thoracic artery from most patients with coronary artery disease. PreproET-1 and hECE-1 mRNA was also detected in VSMCs isolated from these vessels. irET-1 and irvWF staining in endothelium and tunica media was measured by use of microscope-coupled computer-assisted technology. Significant correlations between the amount of irET-1 in the tunica media and mean blood pressure (P<0.05), total serum cholesterol (P<0.05), and number of atherosclerotic sites (P<0.001) were found. Thus, in organ donors, irET-1 was detectable almost exclusively in endothelial cells, whereas in patients with coronary artery disease and/or arterial hypertension, sizable amounts of irET-1 were detectable in the tunica media of different types of arteries. In addition, VSMCs isolated from these vessels coexpressed the preproET-1 and hECE-1 genes. CONCLUSIONS: Collectively, these findings are consistent with the contention that endothelial damage occurs in most patients with atherosclerosis and/or hypertension and that ET-1 is synthesized in VSMCs of these patients.  (+info)

Intranephron distribution and regulation of endothelin-converting enzyme-1 in cyclosporin A-induced acute renal failure in rats. (5/2015)

Endothelin-1 (ET-1) is thought to play a significant role in acute renal failure induced by cyclosporin A (CsA). The cDNA sequence encoding endothelin-converting enzyme-1 (ECE-1), which produces the active form of ET-1 from big ET-1, was recently reported. To elicit the role of ECE-1 in the glomerular and tubular dysfunction induced by CsA, the effects of CsA on mRNA and protein expression of ECE-1 in rat kidney and on mRNA expression of prepro-ET-1 and ET A- and B-type receptors in glomeruli were studied. ECE-1 mRNA was detected in glomeruli and in whole nephron segments. ECE-1 mRNA expression was downregulated in all nephron segments at 24 h after CsA injection. Protein levels were also downregulated in glomeruli and in the outer and inner medulla. CsA rapidly increased prepro-ET-1 mRNA expression in glomeruli at 30 to 60 min after injection; this rapid increase was followed by an increase in plasma ET-1 levels. These increases were followed by decreased expression of ECE-1, ET A-type receptor, and ET B-type receptor mRNA at 6 h after injection, and serum creatinine levels were increased at 24 h after CsA injection. It is suggested that downregulation of glomerular and tubular ECE-1 expression may be caused by increased ET-1 synthesis in CsA-induced acute renal failure.  (+info)

Renin inhibition by substituted piperidines: a novel paradigm for the inhibition of monomeric aspartic proteinases? (6/2015)

BACKGROUND: The aspartic proteinase renin catalyses the first and rate-limiting step in the conversion of angiotensinogen to the hormone angiotensin II, and therefore plays an important physiological role in the regulation of blood pressure. Numerous potent peptidomimetic inhibitors of this important drug target have been developed, but none of these compounds have progressed past clinical phase II trials. Limited oral bioavailability or excessive production costs have prevented these inhibitors from becoming new antihypertensive drugs. We were interested in developing new nonpeptidomimetic renin inhibitors. RESULTS: High-throughput screening of the Roche compound library identified a simple 3, 4-disubstituted piperidine lead compound. We determined the crystal structures of recombinant human renin complexed with two representatives of this new class. Binding of these substituted piperidine derivatives is accompanied by major induced-fit adaptations around the enzyme's active site. CONCLUSIONS: The efficient optimisation of the piperidine inhibitors was facilitated by structural analysis of the renin active site in two renin-inhibitor complexes (some of the piperidine derivatives have picomolar affinities for renin). These structural changes provide the basis for a novel paradigm for inhibition of monomeric aspartic proteinases.  (+info)

Mechanism of the cleavage specificity of Alzheimer's disease gamma-secretase identified by phenylalanine-scanning mutagenesis of the transmembrane domain of the amyloid precursor protein. (7/2015)

Proteolytic processing of the amyloid precursor protein by beta-secretase yields A4CT (C99), which is cleaved further by the as yet unknown gamma-secretase, yielding the beta-amyloid (Abeta) peptide with 40 (Abeta40) or 42 residues (Abeta42). Because the position of gamma-secretase cleavage is crucial for the pathogenesis of Alzheimer's disease, we individually replaced all membrane-domain residues of A4CT outside the Abeta domain with phenylalanine, stably transfected the constructs in COS7 cells, and determined the effect of these mutations on the cleavage specificity of gamma-secretase (Abeta42/Abeta40 ratio). Compared with wild-type A4CT, mutations at Val-44, Ile-47, and Val-50 led to decreased Abeta42/Abeta40 ratios, whereas mutations at Thr-43, Ile-45, Val-46, Leu-49, and Met-51 led to increased Abeta42/Abeta40 ratios. A massive effect was observed for I45F (34-fold increase) making this construct important for the generation of animal models for Alzheimer's disease. Unlike the other mutations, A4CT-V44F was processed mainly to Abeta38, as determined by mass spectrometry. Our data provide a detailed model for the active site of gamma-secretase: gamma-secretase interacts with A4CT by binding to one side of the alpha-helical transmembrane domain of A4CT. Mutations in the transmembrane domain of A4CT interfere with the interaction between gamma-secretase and A4CT and, thus, alter the cleavage specificity of gamma-secretase.  (+info)

In vivo expression and localization of Candida albicans secreted aspartyl proteinases during oral candidiasis in HIV-infected patients. (8/2015)

Isoforms of aspartyl proteinase (Sap), which are encoded by at least nine related SAP genes, have been implicated to be a major virulence factor of the opportunistic yeast Candida albicans in experimental infections. Although it is generally assumed that proteinases are important for infections, detailed information on the pathogenetic role of Saps is still lacking. The same applies to the question whether the genes and corresponding isoforms of the enzyme are expressed during oral infection. For in vivo investigations, parts of the lesional oral epithelium were collected from three HIV-infected patients with oropharyngeal candidiasis. Immunoelectron microscopy was performed (pre- and post-embedding gold labeling with silver enhancement) using an anti-Sap murine monoclonal antibody directed against the gene products Sap1-3. It was possible to demonstrate expression of Sap antigens in each of the three samples of human oral candidiasis. This suggests that at least one of the genes SAP1-3 was expressed at the time of sample collection. Furthermore, a possible role of the enzymes during the interaction of yeast cells and mucosal cells is suggested: the majority of Sap antigens is secreted by those C. albicans cells that adhere directly to the epithelial surface. Sap immunoreactivity can be detected in particular at the site of close contact between C. albicans and epithelial cells, suggesting a pathogenetic role of the Saps in host-fungal interaction. Thus, inhibition of the enzyme might prove to be an important alternative in the prevention and treatment of candidiasis.  (+info)

Meredith, J.E.; Thompson, L.A.; Toyn, J.H.; Marcin, L.; Barten, D.M.; Marcinkeviciene, J.; Kopcho, L.; Kim, Y.; Lin, A.; Guss, V.; Burton, C.; Iben, L.; Polson, C.; Cantone, J.; Ford, M.; Drexler, D.; Fiedler, T.; Lentz, K.A.; Grace, J.E.; Kolb, J.; Corsa, J.; Pierdomenico, M.; Jones, K.; Olson, R.E.; Macor, J.E.; Albright, C.F., 2008: P-glycoprotein efflux and other factors limit brain amyloid beta reduction by beta-site amyloid precursor protein-cleaving enzyme 1 inhibitors in mice
Endothelin-converting enzyme (ECE-1) is a type II integral membrane protein which plays a key role in the biosynthetic pathway of the vasoconstricting endothelins. Three ECE-1 isoforms, differing by their N-terminal cytoplasmic tails, are generated from a single gene. When expressed in CHO cells, they display comparable enzymatic activity but whereas ECE-1a is strongly expressed at the cell surface, ECE-1b is exclusively intracellular and ECE-1c presents an intermediate distribution. In the present study these different localizations were further described at the ultrastructural level, by electron microscope immunocytochemistry. To characterize the motifs responsible for the intracellular localization of ECE-1b we constructed chimeric proteins and point mutants. Two di-leucine-based motifs, contained in the N-terminal part of ECE-1b, were thus identified. One of these motifs (LV), displayed by both ECE-1b and ECE-1c, accounts for the reduced surface expression of ECE-1c as compared to ECE-1a. ...
Secretory aspartyl proteinases (Sap) have long been considered key virulence traits of C. albicans, with rather strong experimental and clinical evidence for a major role in vaginal candidiasis (1, 3). However, the mechanisms by which this family of enzymes is involved in vaginal disease have remained unclear. Sap are active enzymes with a wide range of substrate specificities (26). Since some of these substrates (e.g., complement, histatins, and E-cadherin, and also Abs) play critical roles in both innate and adaptive immune responses, Sap expression is thought to enable the fungus to evade host immunity by enzymatic proteolysis of one or more of the above factors (1, 3). Concurrently, studies in well-established animal models and reconstituted human vaginal epithelia have provided indirect clues for a role of some members of the Sap family in facilitating fungus adherence and penetration into epithelial tissues (27-30). Evidence gathered with the use of anti-Sap Abs supports this proadherence ...
A new aspartic protease from Saccharomyces cerevisiae, with a high degree of similarity with yapsin 1 and yapsin 2 and a specificity for basic residue cleavage sites of prohormones, has been cloned. This enzyme was named yapsin 3. Expression of a C-terminally truncated non-membrane anchored yapsin 3 in yeast yielded a heterogeneous protein between 135-200 kDa which, upon treatment with endoglycosidase H, migrated as a 60 kDa form. Amino-acid analysis of the N-terminus of expressed yapsin 3 revealed two different N-terminal residues, serine-48 and phenylalanine-54, which followed a dibasic and a monobasic residue respectively. Cleavage of several prohormones by non-anchored yapsin 3 revealed a specificity distinct from that of yapsin 1.. ...
Our goal in this work was to determine if signal peptide peptidase is necessary for normal animal development. We present data showing that Drosophila Spp encodes the fly ortholog of human signal peptide peptidase and show that Drosophila Spp provides an essential function required during the larval stages. We also show that SPP is strongly expressed in only a limited set of cells and that the mutant phenotype is consistent with a need for its function in these tissues. Further work will be needed to establish whether the role of Drosophila SPP is a general one that cleanses membranes of signal peptides or if it has specific targets and generates essential products through its action.. Human SPP is an intramembrane aspartyl protease whose active site is predicted to be buried within the lipid bilayer. It belongs to a family of enzymes conserved among animals, plants, and fungi (Ponting et al. 2002; Weihofen et al. 2002). The Drosophila and human SPPs have strong sequence similarity, with the ...
This paper focuses deals with the cleavage of NaVβ2 via BACE-1 (Beta-site APP-cleaving enzyme 1), leading to increased NaV1.1 levels, which do not translocate to the cell plasma membrane. Reinforcing that decreased NaV1.1 levels are involved in AD development/progression. This work cites the use of Alomone Labs Anti-SCN1A (NaV1.1) Antibody (#ASC-001) and Anti-NaVβ2 Antibody (#ASC-007).. The early stages of Alzheimers disease (AD), an incurable neurological affliction with adverse effects on memory and cognition, are often accompanied by aberrant neuronal activity and epileptic seizures - events which are increasingly seen as having a direct influence on ADs progression. Cortical accumulation of amyloid β (Aβ), a peptide derived from amyloid precursor protein (APP), seems to play a prominent role on the onset of AD. Beta-site APP-cleaving enzyme 1 (BACE1) - the rate-determining factor in Aβ synthesis - is significantly high in both AD patients and APP mice (transgenic line with ...
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Intramembrane proteases cleave peptide bonds within cellular membranes and thereby control important processes ranging from transcription regulation to growth factor secretion (Lemberg, 2011). The largest and most diverse group of these unusual enzymes is formed by the GxGD aspartyl proteases including presenilin/γ‐secretase as well as signal peptide peptidase (SPP) (Wolfe, 2009; Lichtenthaler et al, 2011). SPP localizes to the endoplasmic reticulum (ER) where it cleaves signal peptides that have been removed from precursors of secretory and membrane proteins (Weihofen et al, 2002). Like for most characterized intramembrane proteases, this release is part of a two‐step mechanism: First signal peptidase cleaves off the substrate proteins ectodomains, which enables the subsequent SPP‐catalyzed intramembrane cut (Lemberg & Martoglio, 2002). So far, known functions of SPP include generation of signal peptide‐derived bioactive peptides in immune surveillance and proteolytic maturation of ...
In molecular biology, the Signal Peptide Peptidase (SPP) is a type of protein that specifically cleaves parts of other proteins. It is an intramembrane aspartyl protease with the conserved active site motifs YD and GxGD in adjacent transmembrane domains (TMDs). Its sequences is highly conserved in different vertebrate species. SPP cleaves remnant signal peptides left behind in membrane by the action of signal peptidase and also plays key roles in immune surveillance and the maturation of certain viral proteins. Physiologically SPP processes signal peptides of classical MHC class I preproteins. A nine amino acid-long cleavage fragment is then presented on HLA-E receptors and modulates the activity of natural killer cells. SPP also plays a pathophysiological role; it cleaves the structural nucleocapsid protein (also known as core protein) of the Hepatitis C virus and thus influences viral reproduction rate. In mice, a nonamer peptide originating from the SPP protein serves as minor ...
3RTM: From Fragment Screening to In Vivo Efficacy: Optimization of a Series of 2-Aminoquinolines as Potent Inhibitors of Beta-Site Amyloid Precursor Protein Cleaving Enzyme 1 (BACE1).
PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
A phosphoramidon-sensitive metalloendopeptidase in peptidase family M13 (neprilysin family). An integral membrane protein predominantly of endothelial cells, which genera
BACE1 - BACE1 (untagged)-Human beta-site APP-cleaving enzyme 1 (BACE1), transcript variant a available for purchase from OriGene - Your Gene Company.
Isoform Delta of Protachykinin-1 contains a PF02202 domain.. Isoform Delta of Protachykinin-1 contains a PF02202 domain.. Isoform Delta of Protachykinin-1 is proteolytically cut by dipeptidyl-peptidase II (S28.002) cleavage. --RP-KPQQ.. Isoform Delta of Protachykinin-1 is proteolytically cut by (S9F.001) cleavage. FFGL-MNH2--.. Isoform Delta of Protachykinin-1 is proteolytically cut by penicillolysin (M35.001) cleavage. RPKP-QQFF.. Isoform Delta of Protachykinin-1 is proteolytically cut by aminopeptidase P1 (M24.009) cleavage. ---R-PKPQ.. Isoform Delta of Protachykinin-1 is proteolytically cut by endothelin-converting enzyme 1 (M13.002) cleavage. PQQF-FGLM.. Isoform Delta of Protachykinin-1 is proteolytically cut by endothelin-converting enzyme 1 (M13.002) cleavage. KPQQ-FFGL.. Isoform Delta of Protachykinin-1 is proteolytically cut by neprilysin (M13.001) cleavage. PQQF-FGLM.. Isoform Delta of Protachykinin-1 is proteolytically cut by neprilysin (M13.001) cleavage. KPQQ-FFGL.. Isoform Delta of ...
Multiple myeloma (MM) can be an indolent B-cell disease that develops in the bone tissue marrow and it is connected with osteolytic lesions in 1174043-16-3 the advanced phases [1]. site thats turned on in Tyr1356 and Tyr1349. The phosphorylation of the region leads to the induction of MET signaling through the activation of many downstream …Read More. ...
Intramembrane proteolysis, Alzheimer´s disease, Parkinsons disease, type-2 diabetes, γ-secretase, signal peptide peptidase , substrate enzym interactions, TMD, DFG Verbundprojekt, Lemberg, Fluhrer, Lichtenthaler, Steiner, Langosch, Haass, Frishman, Scharnagl, Luy, Huster,
1OEX: Atomic Resolution Analysis of the Catalytic Site of an Aspartic Proteinase and an Unexpected Mode of Binding by Short Peptides
Complete information for SPPL3 gene (Protein Coding), Signal Peptide Peptidase Like 3, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
Complete information for SPPL2B gene (Protein Coding), Signal Peptide Peptidase Like 2B, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
Vitae Pharmaceuticals BACE inhibitor, VTP-37948, lowered cerebrospinal fluid Aβ by up to 80 percent in healthy volunteers, according to topline data from a Phase 1 clinical trial. A second Phase 1 trial that used a single-ascending-dose strategy suggested that volunteers tolerated the drug well. Vitae chief scientific officer Richard Gregg told Alzforum that the companies will soon test the inhibitor in multiple rising dose trials. Results should be available early next year, said Vitae CEO Jeffrey Hatfield. The company will develop the inhibitor, also known as BI 1181181, in partnership with Boehringer Ingelheim.. Vitae used a structure-based approach to develop the drug, which fits the catalytic pocket of the aspartyl protease. VTP-37948 joins BACE inhibitors being developed by other pharmaceutical companies including Merck, AstraZeneca/Lilly, and Novartis. The Vitae inhibitor, like the other compounds under development, does not discriminate between β-secretase isoforms, blocking both ...
Ece1 - Ece1 (untagged) - Mouse endothelin converting enzyme 1 (Ece1), (10ug) available for purchase from OriGene - Your Gene Company.
ECE1 overexpression lysate, 0.1 mg. Transient overexpression lysate of endothelin converting enzyme 1 (ECE1), transcript variant 1
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The present invention provides compounds having the formula: wherein R1, R′, R2, R3, R3′, R4, X1, X2 and X3 are as defined herein, and pharmaceutical compositions thereof. The present invention also provides methods of inhibiting proteases, more specifically aspartyl proteases. In certain embodiments, compounds inhibit BACE (β-site APP-cleaving enzyme), and thus are useful in the treatment or prevention of a disease characterized by β-amyloid deposits in the brain (including, but not limited to, Alzheimers Disease). The present invention also provides methods for preparing compounds of the invention.
The present study describes a novel sensitive live-cell assay for studying ECE activity. ET-1 is formed from its precursor preproET-1 via the cleavage of the intermediate bigET-1 by ECE-1. However, the subcellular site at which this step occurs is not clear: It could occur intravesicularly along the secretory pathway or bigET-1 may be released and processed extracellularly. To address this point, we have developed an integrated autocrine system.. Until now, ECE activity has been evaluated in solubilized membrane fractions by high-performance liquid chromatography assays,32 immunoassays,12 fluorogenic determinations,33 receptor assays,34 and fluorescence polarization assays.35 Most of these assays require an incubation in vitro with high concentrations of substrate, and all of them need an independent second step to measure the product, ET-1.. In the present study, a recombinant CHO reporter cell line permanently expressing the human ETA receptor and a reporter gene sensitive to its activation ...
cansSAR 3D Structure of 2OHR | X-RAY CRYSTAL STRUCTURE OF BETA SECRETASE COMPLEXED WITH COMPOUND 6A | 2OHR_A | Beta-secretase 1 - Also known as BACE1_HUMAN, BACE1, BACE, KIAA1149. Responsible for the proteolytic processing of the amyloid precursor protein (APP). Cleaves at the N-terminus of the A-beta peptide sequence, between residues 671 and 672 of APP, leads to the generation and extracellular release of beta-cleaved soluble APP, and a corresponding cell-associated C-terminal fragment which is later released by gamma-secretase (PubMed:10656250, PubMed:10677483, PubMed:20354142). Cleaves CHL1 (By similarity). Monomer. Interacts (via DXXLL motif) with GGA1, GGA2 and GGA3 (via their VHS domain); the interaction highly increases when BACE1 is phosphorylated at Ser-498 (PubMed:14567678, PubMed:15886016). Interacts with RTN3 and RTN4 (PubMed:15286784, PubMed:16965550, PubMed:16979658). Interacts with SNX6 (PubMed:20354142). Interacts with PCSK9 (PubMed:18660751). Interacts with NAT8 and NAT8B (PubMed
Alzheimers disease (AD) is characterized by extracellular accumulation of amyloid-β peptide (Aβ), generated by proteolytic processing of the amyloid precursor protein (APP) by β- and γ-secretase. Aβ generation is inhibited when the initial ectodomain shedding is caused by α-secretase, cleaving APP within the Aβ domain. Therefore, an increase in α-secretase activity is an attractive therapeutic target for AD treatment. APP and the APP-cleaving secretases are all transmembrane proteins, thus local membrane lipid composition is proposed to influence APP processing. Although several studies have focused on γ-secretase, the effect of the membrane lipid microenvironment on α-secretase is poorly understood. In the present study, we systematically investigated the effect of fatty acid (FA) acyl chain length (10:0, 12:0, 14:0, 16:0, 18:0, 20:0, 22:0, 24:0), membrane polar lipid headgroup (phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine), saturation grade and the FA double-bond
Signal sequences are the addresses of proteins destined for secretion. In eukaryotic cells, they mediate targeting to the endoplasmic reticulum membrane and insertion into the translocon. Thereafter, signal sequences are cleaved from the pre-protein and liberated into the endoplasmic reticulum membrane. We have recently reported that some liberated signal peptides are further processed by the intramembrane-cleaving aspartic protease signal peptide peptidase. Cleavage in the membrane-spanning portion of the signal peptide promotes the release of signal peptide fragments from the lipid bilayer. Typical processes that include intramembrane proteolysis is the regulatory or signalling function of cleavage products. Likewise, signal peptide fragments liberated upon intramembrane cleavage may promote such post-targeting functions in the cell.. ...
Novel Aspartic Proteinase of the PepSIN Family (Napsin A, or NAPSA) belongs to the peptidase A1 family and plays a role in pneumocyte surfactant processing. It is also known as aspartyl protease 4 (ASP4), KAP, Kdap, napsin-1, NAP1, NAPA, and SNAPA. Two closely related proteins are known, Napsin A and Napsin B. Napsin A is a single-chain, 38-kDa protein. It is expressed at high levels in human lung and kidney, and at lower levels in spleen. Napsin A expression has been detected in type II pneumocytes and in lung adenocarcinomas.. ...
www.MOLUNA.de Aspartic Proteinases [4193983] - The 5th International Conference on Aspartic Proteinases was held on September 19 through 24, 1993, at Naito Museum of Pharmaceutical Science and Industry, Kawashima cho, Gifu Prefecture, Japan, about 15 miles northwest of Nagoya City. About 100 scientists attended the conference, including 52 from 14 countries outside Japan, and 32
X-converting enzyme (XCE) involved in nervous control of respiration, is a member of the M13 family of zinc peptidases, for which no natural substrate has been identified yet. In contrast, its well characterized homologue endothelin-converting enzyme-1 (ECE-1) showed broad substrate specificity and acts as endopeptidase as well as dipeptidase. To explore the structural differences between XCE and ECE-1, homology model of XCE was built using the complex structure of ECE-1 with phosphoramidon (pdb-id: 3DWB) as template. Phosphoramidon was docked into the binding site of XCE whereas phosphate oxygen of the inhibitor was used as water molecule to design the apo forms of both enzymes. Molecular dynamics simulation of both enzymes was performed to analyze the dynamic nature of their active site residues in the absence and presence of the inhibitor. Homology model of XCE explained the role of non-conserved residues of its S2 subsite. Molecular dynamics (MD) simulations identified the flexible transitions of
Integral membrane proteins (ECEs) that are zinc-binding metallopeptidases of the same family as neprilysin with a role in processing various neuropeptides. ECE-1 (EC 3.4.24.71, 770 aa) converts big endothelin-1 (ET-1) to active ET-1 and is important in regulating blood pressure. Isoforms of endothelin-converting enzyme-1 (ECE-1a-d) are present in early endosomes, where they degrade various neuropeptides and regulate postendocytic sorting of receptors. Defects in the ECE-1 gene are associated with Hirschsprungs disease. ECE-2 (883 aa) has been implicated in Alzheimers disease and knockout mice show deficiencies in learning and memory. ...
Beta Secretase Substrate Functional Assay Kits datasheet (ab101160). Abcam offers quality products including antibodies, assays and other reagents.
Hypertension is largely attributed to abnormal renal sodium handling; however, a growing body of evidence now suggests that primary abnormalities in vessels can also cause aberrations in blood pressure. Very often, the source of the abnormality resides in the endothelial cells that regulate the functional state of the entire vessel, and this knowledge has directed our search for new diagnostic and therapeutic targets. To date, the role of transcriptional mechanisms in blood pressure regulation is poorly characterized. In this study, we found that E2F2, a transcription factor involved in cell-cycle control, regulates blood pressure by modulating vessel contractility. This previously unknown function of E2F2 evolves from the unique role of the molecule in endothelial cells: suppression of endothelin-converting enzyme 1 (ECE-1). ECE-1 converts the inactive precursor molecule big endothelin-1 into the potent vasoconstrictor endothelin-1, and genetic deletion of E2F2 in mice was associated with both ...
Hansson CA, Frykman S, Farmery MR, Tjernberg LO, Nilsberth C, Pursglove SE, Ito A, Winblad B, Cowburn RF, Thyberg J, Ankarcrona M. Nicastrin, presenilin, APH-1, and PEN-2 form active gamma-secretase complexes in mitochondria ...
Regulated intramembrane proteolysis is certainly a central mobile practice included in sign membrane layer and transduction proteins turnover. condition of MHCII-containing endosomes, highlighting SPPL2a as a possible medicinal focus on for using up and/or modulating T cells. The concept of intramembrane proteases (I-CLIPs) cleaving within the phospholipid bilayer was originally place forwards structured on digesting of the sterol regulatory elementCbinding proteins (SREBP; Goldstein and Brown, 1997; Kopan and Wolfe, 2004). Generally, I-CLIPs operate as component of a proteolytic series known to as governed intramembrane proteolysis (Split; Lichtenthaler et al., 2011). Intracellular websites (ICDs) of many Split substrates function as signaling elements after their proteolytic discharge as exemplified by the Level path (De Strooper et al., 1999; Freeman and Urban, 2002). Structured on their catalytic middle, serine, metallo, or aspartyl I-CLIPs (Wolfe, 2009) can end up being differentiated. The ...
The study and understanding of Alzheimers disease on protein level is fundamentally important in the search for its treatment and there is a demand for proteins that can be used together with candidate drugs in crystallography trials. The refolding time reaching up to three weeks for beta-site APP cleaving enzyme 1 (BACE1), the proposed disease-generating protein, is presently not optimal and new protein constructs are needed. In attempts to shorten the refolding time the six cysteins in BACE1 were substituted to hydrophobic valine or alanine residues. The proteins, both wild type and mutant BACE1, were expressed in Escherichia coli, refolded for one week and purified by ion exchange chromatography and gel filtration. The final products were characterised by measuring stability, homogeneity and enzyme activity. There was significantly lower protein yield for the mutants compared to the wild type BACE1, indicating that generation of the disulphide bonds are important for correctly folded and ...
The neurons of the sympathetic nervous system have distinct properties that allow them to regulate a particular end organ. Various models have been proposed to explain how such precise wiring of neurons to their synaptic targets might come about during development. The neurons might grow in a relatively random manner and then adopt appropriate characteristics after interacting with their target tissue, or there might be molecular markers that guide particular neurons to the right target. Makita et al. provide new evidence in favor of the latter scheme for a set of neurons of the superior cervical ganglia (SCG) that follow along the external carotid artery to reach their salivary gland targets. The authors examined mRNA from external carotid artery in microarray analysis to search for expression of transcripts that might encode guidance molecules. They found specific expression of mRNA encoding endothelin-converting enzyme (which converts precursors of endothelin into the active form). ...
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Rabbit polyclonal antibody raised against synthetic peptide of BACE1. A synthetic peptide corresponding to C-terminus of human BACE1. (PAB9981) - Products - Abnova
Liu et al. describe a previously unrecognized cellular complex (∼5 MD) containing β- and γ-secretases that generates a full array of Aβ peptides with physiological Aβ42/40 ratios by sequential cleavages of holo-APP. Such coordinated substrate processing also occurs with the α- and γ-secretases in the RIP mechanism.. ...
Supplementary MaterialsVideo 1 Time-lapse imaging cells expressing both mt-roGFP and Smac mCherry treated with cisplatin stably. with an indicated medication with 10?nm of TMRM. Live cell imaging was TMP 269 biological activity completed as defined. mmc6.mp4 (20M) GUID:?20E6FE9E-0743-40DF-9A25-5E8A9CEF2F51 TMP 269 biological activity Video 7 EGCG: U2Operating-system cells stably expressing mt-roGFP were stained with TMRM to […]. ...
View Notes - ece302hw8 from ECE ECE 302 at Cal Poly Pomona. 3:32 we g (a) Find H in rectangular components at P(2, 3, 4) if there is a current filament on the z axis carrying 8rnA in the aZ
Buy our BACE1 peptide. Ab7883 is a blocking peptide and has been validated in BL. Abcam provides free protocols, tips and expert support for WB and a 12 month…
Background Icaritin (ICT) is a prenylflavonoid derivative from Epimedium brevicornum Maxim. ICT has been shown to have neuroprotective effects. We investigate how ICT affects secretion of amyloid precursor protein (APP). Methods We exposed APP-PS1-HEK293 cells to ICT to investigate its effect on beta-site amyloid cleaving enzyme (BACE)1. Cell viability was evaluated by MTT and lactate dehydrogenase (LDH) assays. The half-maximal inhibitory concentration (IC50) of ICT for BACE1 was measured using fluorescence resonance energy transfer. Effects of ICT on the mRNA expression of APP were assessed by quantitative polymerase chain reaction, and protein expression was measured by western blotting and immunofluorescence. Results Icaritin inhibited BACE1 activity and IC50 was 5.70 ± 1.09 μM. Compared with the control group, at ICT concentrations of 5 μM and 10 μM, the viability increased and LDH leakage decreased in APP-PS1-293 cells. Also, mRNA expression of A disintegrin and metalloproteinase domain
Coffee made from the roasted seeds of the genus Coffee, belonging to the family Rubiaceae native to southern Arabia. Coffee may consist certain substances, effecting the risk of Alzheimers disease. AD mice given caffeine in their drinking water from young adulthood into older age showed to inhibit memory and cognitive impairment and lower brain levels of amyloid-beta; Abeta)(24)(25). In mice with Alzheimers disease caused by dysregulated endoplasmic reticulum (ER) calcium (Ca 2+), induced deletion of RyanR3, showed the enhancement of coffee in activation of RyanRs which protected AD neurons from synaptic and network dysfunction(26). Intake of 5 cups of coffee per day(moderate caffeine intake) found to protect against the development of certain cognitive impairment and decreased hippocampal amyloid-beta (Abeta) levels through suppression of both beta-secretase (BACE1), a beta-site amyloid precursor protein cleaving enzyme 1 and presenilin 1 (PS1)/gamma-secretase expression(mutations in the ...
Aspartic proteases are important virulence factors in pathogens like HIV, Candida albicans or Plasmodium falciparum. We report here the identification of seven putative aspartic proteases, TgASP1 to TgASP7, in the apicomplexan parasite Toxoplasma gondii. Bioinformatic and phylogenetic analysis of the TgASPs and other aspartic proteases from related Apicomplexa suggests the existence of five distinct groups of aspartic proteases with different evolutionary lineages. The members of each group share predicted biological features that validate the phylogeny. TgASP1 is expressed in tachyzoites, the rapidly dividing asexual stage of T.gondii. We present the proteolytic maturation and subcellular localization of this protease through the cell cycle. TgASP1 shows a novel punctate localization associated with the secretory system in non-dividing cells, and relocalizes dramatically and unambiguously to the nascent inner membrane complex of daughter cells at replication, before coalescing again at the end ...
Peptides , Cyclic Peptides , Disulfide Cyclized Peptides , Big Endothelin-1 (1-38), human; Big Endothelin-1 (1-38) is precursor of endothelin 1. Big endothelin-1 is cleaved to yield endothelin-1 via the activity of an endothelin-converting enzyme (ECE). Big Endothelin-1 can be hydrolyzed by chymase to generate endothelin 1 (1-21) in vitro. Endothelins are endothelium-derived vasoconstrictor peptides.; CSCSSLMDKECVYFCHLDIIWVNTPEHVVPYGLGSPRS (Disulfide bridge: 1-15 and 3-11); H-Cys-Ser-Cys-Ser-Ser-Leu-Met-Asp-Lys-Glu-Cys-Val-Tyr-Phe-Cys-His-Leu-Asp-Ile-Ile-Trp-Val-Asn-Thr-Pro-Glu-His-Val-Val-Pro-Tyr-Gly-Leu-Gly-Ser-Pro-Arg-Ser-OH (Disulfide bridge: 1-15 and 3-11)
0034] Memapsin 2 (BACE1, β-secretase) is a membrane anchored aspartic protease. Although this enzyme is ubiquitously present in many mammalian organs, its functions in the brain are best studied. One of the most important physiological functions of memapsin 2 is the cleavage of a brain membrane protein β-amyloid precursor protein (APP). The hydrolytic product of APP C-terminal fragment is cleaved again by an intramembrane protease γ-secretase to generate a 40- or 42-residue β-amyloid peptide (Ar). Aβ has been shown to feedback down regulate the synaptic activity in neurons (Kamenetz et al., 2003; Lauren et al., 2009). Also, memapsin 2 produced APP N-terminal fragment is involved in the trimming of neurons and axons in the brain (Nikolaev et al., 2009). However, since excess levels of brain Aβ are intimately related to the pathogenesis of Alzheimers disease (Selkoe, 1999), there has been intensive effort to develop inhibitor drugs against memapsin 2 (Ghosh et al., 2008). Important to such ...
293476355 - EP 1030911 A1 2000-08-30 - HUMAN ASPARTIC PROTEASES - [origin: WO0004137A1] The invention provides human aspartic proteases (NHAP) and polynucleotides which identify and encode NHAP. The invention also provides expression vectors, host cells, antibodies, agonists, and antagonists. The invention also provides methods for diagnosing, treating or preventing disorders associated with expression of NHAP.[origin: WO0004137A1] The invention provides human aspartic proteases (NHAP) and polynucleotides which identify and encode NHAP. The invention also provides expression vectors, host cells, antibodies, agonists, and antagonists. The invention also provides methods for diagnosing, treating or preventing disorders associated with expression of NHAP.
β-Secretase (BACE) is a membrane-bound aspartyl protease that cleaves the amyloid precursor protein and is consequently an excellent target for anti-amyloid therapy in the treatment of Alzheimers disease. Finding inhibitors of β-secretase is one of the major goals of Alzheimers disease drug development. PromoKines β-Secretase Fluorometric Assay Kit provides a convenient, non-radioactive system for detecting β-Secretase activity in biological samples. The kit provides active β-Secretase as positive control, β-Secretase inhibitor as negative control, optimized peptide substrate (conjugated to two reporter molecules), and buffers for convenient measurement of β-Secretase activity in mammalian samples. β-Secretase inhibitors are also available separately. ...
Essential subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral membrane proteins such as Notch receptors and APP (amyloid-beta precursor protein) (PubMed:12522139, PubMed:12763021, PubMed:12740439, PubMed:12679784, PubMed:24941111). The gamma-secretase complex plays a role in Notch and Wnt signaling cascades and regulation of downstream processes via its role in processing key regulatory proteins, and by regulating cytosolic CTNNB1 levels (Probable). PSENEN modulates both endoproteolysis of presenilin and gamma-secretase activity (PubMed:12522139, PubMed:12763021, PubMed:12740439, PubMed:12679784, PubMed:24941111).
Disclosed are various forms of an active, isolated β-secretase enzyme in purified and recombinant form. This enzyme is implicated in the production of amyloid plaque components which accumulate in the
This thesis describes the synthesis of molecules designed for inhibition of two aspartic proteases, viral HIV-1 PR and human BACE-1. It also reports on the structure activity relationships of the targeted enzyme inhibitors.. It is estimated that currently 33 million people are infected with HIV, the causative agent of AIDS. The virus targets T-lymphocytes and macrophages of the human immune system. The HIV-1 PR plays an important role in the viral replication, and by inhibiting the enzyme the disease progression can be slowed down or even halted.. Herein is reported the design and synthesis of a series of HIV-1 PR inhibitors with novel P2 substituents of which several inhibit the enzyme in the nanomolar range. The aim of the second work was to further develop the inhibitors by the introduction of fluorine. Several attempts were performed to fluorinate different P2-substituents.. Alzheimers disease (AD) is neurodegenerative, progressive and fatal disorder of the brain. It is associated with ...
Aspartic proteinases are a group of enzymes functioning by a general base mechanism, the water molecule serving as nucleophile.1The X-ray data (for example references 2-4) clearly show that two...
We have used the confocal microscope to analyze the subcellular distribution of the APH-1 protein in early embryos of C. elegans. APH-1 is one of four protein members of the gamma-secretase complex, which achieves intramembranous cleavage of a variety of target membrane proteins. Although the effect in protein cleavage is clear, the site of gamma-secretase assembly and function within the cell remains elusive. We use the early C. elegans embryo as the context in which to analyze protein localization because the cells are relatively large, and because the four-cell embryo is the site of a well-defined event of Notch signaling that has been shown to be entirely dependent on gamma-secretase activity. Our analysis of wild type C. elegans embryos shows that the APH-1 protein is present at the plasma membrane in early embryos. This location is consistent with the role of gamma-secretase in targeting the Notch receptor after it has interacted with its ligand on an adjacent cell, and is also consistent ...
New from HCP Formulas, Fibrenza is a blend of fourteen unique systemic enzymes that have been specifically formulated to dissolve fibrin, cleanse the blood, maintain a healthy inflammatory response, and to detoxify the body. Comprised of pharmaceutical grade enzymes, Fibrenza contains the most effective enzymes available today. I personally found this product very helpful for helping my incisions and breast tissue heal very nicely after explant.. Ultra-Premium Systemic Enzymes. Fibrenza contains one of the most expensive and effective enzyme ingredients available. Seaprose-S is a protein-cleaving enzyme that is one of the strongest anti-inflammatory oral enzymes available today. Clinical Studies show it to be even more effective at fighting inflammation than serratiopeptidase. Nattokinase NSK-SD is another proteolytic enzyme that is taken to maintain cardiovascular health due to its blood-cleansing and fibrin dissolving effects.. Serrapeptase (Serratiopeptidase), Acid Stable Protease, Bromelain, ...
Nicastrin is a Type I transmembrane glycoprotein. Along with presenilin, APH-1, PEN-2, it comprises the multimeric gamma-secretase complex. The gamma-secretase complex can cleave the beta-amyloid (A4) precursor protein and yields amyloid beta peptide, the main component of the neuritic plaque a...
Jeon AH, Böhm C, Chen F, Huo H, Ruan X, Ren CH, Ho K, Qamar S, Mathews PM, Fraser PE, Mount HT, St George-Hyslop P, Schmitt-Ulms G. Interactome analyses of mature γ-secretase complexes reveal distinct molecular environments of presenilin (PS) paralogs and preferential binding of signal peptide peptidase to PS2. J Biol Chem. 2013 May 24;288(21):15352-66. doi: 10.1074/jbc.M112.441840. PMID: 23589300 PMCID: PMC3663554 Click for abstract ...
This thesis describes work done to design and synthesize protease inhibitors, with the intention of developing therapeutic agents for Alzheimers disease (AD) and the chronic liver condition caused by infection of the hepatitis C virus (HCV). AD is the most common form of dementia, and HCV infection is the primary reason for liver transplantation in industrialized countries. Today, these two illnesses affect 24 and 170 million people, respectively. It has been shown that the human aspartic protease BACE-1 plays an important role in the development of AD, and thus inhibition of BACE-1 may offer a way to improve the quality of life of individuals afflicted with the disease. Furthermore, it is known that the serine protease NS3 is a vital component in the replication of HCV.. Several novel potent BACE-1 inhibitors encompassing different transition state mimics were prepared. First, a hydroxyethylene moiety encompassing a secondary hydroxyl group was evaluated as a transition state analogue, ...
Reactome is pathway database which provides intuitive bioinformatics tools for the visualisation, interpretation and analysis of pathway knowledge.
Supplementary MaterialsAdditional document 1: Figure S1. in blue (related to Figure ?Figure22). 12974_2019_1582_MOESM3_ESM.mp4 (34M) GUID:?5E2C8E2F-16E2-44C5-8442-6D29BA744B63 Additional file 4: Video S3. Representative video depicting Iba1 immunoreactivity in a 1?mm thick hippocampal section cleared using CLARITY from a URMC-099-treated surgical mouse (Video S3). All mice were 3-month-old for this experiment. Iba1 is denoted in red; DAPI in […]. ...
Sarmento AC, Lopes H, Oliveira CS, Vitorino R, Samyn B, Sergeant K, Debyser G, Van Beeumen J, Domingues P, Amado F, Pires E, Domingues MRM, Barros MT. (2009). Multiplicity of aspartic proteinases from Cynara cardunculus L. Planta: 230 (2), 429 ...
View Notes - 07W-midterm-sol from ECE ece 65 at UCSD. ECE65 (Winter 2007), Midterm Name: Notes: 1. Write your answers on these three sheets. 2. For each problem, 20% of points are alloacted for the
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Yes indeed, Merck announced last night that the first Phase III trial of their beta-secretase (BACE) inhibitor verubecestat was stopped because of futility. The
Cell Lines, Hydrogen, Lead, Amyloid, Disease, Electronic, Evaluation, Inhibition, Mutation, Secretase, Secretases, At 10, Breast, Breast Cancer, Cancer, Cancers, Cell, Cell Viabilities, Cell Viability, Cells
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ECE 653 Embedded and Real-Time Systems ΧΑΡΗΣ ΘΕΟΧΑΡΙΔΗΣ Επίκουρος Καθηγητής ΗΜΜΥ Slides partially adopted from Prof. Peter Marwedel Spring 2015 ΔΙΑΛΕΞΗ 1: Εισαγωγή ΗΜΥ653 Δ01
C Giavoli; E Ferrante; E Profka; L Olgiati; S Bergamaschi; C Ronchi; E Verrua; M Filopanti; E Passeri; L Montefusco; A Lania; S Corbetta; M Arosio; B Ambrosi; A Spada; P Beck-Peccoz ...
Bacillus sp. strain Wp22.A1 produced a cell-associated aspartic proteinase which was purified to homogeneity using phenyl-Sepharose (hydrophobic and affinity chromatography) and Mono Q. The proteinase has a molecular mass of 45 kDa by SDS/PAGE and a pI of 3.8. It is insensitive to pepstatin, but is sensitive to the other aspartic proteinase-specific inhibitors diazoacetyl-DL-norleucine methyl ester (DAN) and 1,2-epoxy-3-(p-nitrophenoxy)propane. Inactivation by DAN was only partial, suggesting that it had non-specifically modified an aspartate residue at a site other than the active site. The enzyme was not inhibited by any of the serine or cysteine proteinase inhibitors tested. Maximum proteolytic activity was observed at pH 3.5. The proteinase had a higher activity with haemoglobin, but was more specific (Vmax./Km) for cytochrome c. Substrate inhibition was observed with both these substrates. The cleavage of oxidized insulin B chain tended to occur at sites where the P1 amino acid was bulky ...
Increased amyloid-β (Aβ) load in the brain, neurite degeneration, neuronal loss, and decreased levels of several neurotrophins are among the characteristics of Alzheimers disease (AD). Generation of Aβ occurs when the amyloid precursor protein (APP) is proteolytically processed by β- and γ-secretases in the amyloidogenic pathway. However, Aβ formation is prevented if APP is cleaved by α- and γ- secretases in the non-amyloidogenic pathway. The normal function of APP is still not fully known. It seems clear that the different fragments that are produced during proteolytic processing have different bioactive properties. APP and its metabolites have been implicated in neurite outgrowth, synaptogenesis, cell adhesion, neuroprotection and apoptosis.. The aim of this thesis was to investigate how neurotrophic factors affect the synthesis and processing of APP and its two mammalian paralogues the APP-like protein-1 and-2 (APLP1 and APLP2). We also wanted to determine how the expression levels ...
The aggregation of the amyloid-β (Aβ; see Drosophila Appl) peptide into fibrillar deposits has long been considered the key neuropathological hallmark of Alzheimers disease (AD). Aβ peptides are generated from proteolytic processing of the transmembrane Aβ precursor protein (AβPP) via sequential proteolysis through the β-secretase activity of β-site AβPP-cleaving enzyme (BACE1) and by the intramembranous enzyme γ-secretase. For over a decade, Drosophila melanogaster has been used as a model organism to study AD, and two different approaches have been developed to investigate the toxicity caused by AD-associated gene products in vivo. In one model, the Aβ peptide is directly over-expressed fused to a signal peptide, allowing secretion of the peptide into the extracellular space. In the other model, human AβPP is co-expressed with human BACE1, resulting in production of the Aβ peptide through the processing of AβPP by BACE1 and by endogenous fly γ-secretase. This study consisted of ...
Looking for online definition of Acid Protease in the Medical Dictionary? Acid Protease explanation free. What is Acid Protease? Meaning of Acid Protease medical term. What does Acid Protease mean?
BioAssay record AID 144358 submitted by ChEMBL: Compound was tested for the inhibition of 1-40 beta-Amyloid Production in N9 cell line expressing beta-APP (wascreated by transfecting the human cDNA encoding beta-APP 695) by using immunoprecipitation assay.
cansSAR 3D Structure of 5HDX | BACE-1 IN COMPLEX WITH (7AR)-7A-(5-CYANOTHIOPHEN-2-YL)-6-(4-ETHOXY-5- FLUORO-6-METHYLPYRIMIDIN-2-YL)-3-METHYL-4-OXOOCTAHYDRO-2H-PYRROLO[3, 4-D]PYRIMIDIN-2-IMINIUM | 5HDX_A | Beta-secretase 1 - Also known as BACE1_HUMAN, BACE1, BACE, KIAA1149. Responsible for the proteolytic processing of the amyloid precursor protein (APP). Cleaves at the N-terminus of the A-beta peptide sequence, between residues 671 and 672 of APP, leads to the generation and extracellular release of beta-cleaved soluble APP, and a corresponding cell-associated C-terminal fragment which is later released by gamma-secretase (PubMed:10656250, PubMed:10677483, PubMed:20354142). Cleaves CHL1 (By similarity). Monomer. Interacts (via DXXLL motif) with GGA1, GGA2 and GGA3 (via their VHS domain); the interaction highly increases when BACE1 is phosphorylated at Ser-498 (PubMed:14567678, PubMed:15886016). Interacts with RTN3 and RTN4 (PubMed:15286784, PubMed:16965550, PubMed:16979658). Interacts with SNX6 (PubMed
Johnson & Johnsons Janssen division has decided to halt the Phase II-III EARLY clinical trial (NCT02569398) of its Alzheimers disease (AD) candidate atabacestat (JNJ-54861911), a Beta-Secretase (BACE) inhibitor, due to safety... ...
The β/γ Secretase Antibody Sampler Kit offers flexibility for sampling and detection of β- and γ-secretase proteases that are essential components in the processing of amyloid precursor protein and generation of amyloid beta peptide.
Regulated intramembrane proteolysis is certainly a central mobile practice included in sign membrane layer and transduction proteins turnover. condition of MHCII-containing endosomes, highlighting SPPL2a as a possible medicinal focus on for using up and/or modulating T cells. The concept of intramembrane proteases (I-CLIPs) cleaving within the phospholipid bilayer was originally place forwards structured on digesting of the sterol regulatory elementCbinding proteins (SREBP; Goldstein and Brown, 1997; Kopan and Wolfe, 2004). Generally, I-CLIPs operate as component of a proteolytic series known to as governed intramembrane proteolysis (Split; Lichtenthaler et al., 2011). Intracellular websites (ICDs) of many Split substrates function as signaling elements after their proteolytic discharge as exemplified by the Level path (De Strooper et al., 1999; Freeman and Urban, 2002). Structured on their catalytic middle, serine, metallo, or aspartyl I-CLIPs (Wolfe, 2009) can end up being differentiated. The ...
Determined that modestly reducing levels of two enzymes in the brain, BACE-1 and γ-secretase, reduced Aß accumulation and improved cognition in a mouse model of AD. BACE-1 and γ-secretase are involved in generating Aß from amyloid precursor protein and are therapeutic targets for AD. However, large reductions and/or strong inhibition of these enzymes have been associated with unfortunate side effects in animal models. Previous animal studies have demonstrated that more modest reductions in either of these proteins alone reduces side effects but provides only mild protection against accumulation of Aß. These results suggest that a combination therapy that moderately inhibits both proteins could potentially be both safe and more effective than therapies that target only one of these proteins.8 ...
Pepstatin is a strong inhibitor for all acid proteases. It does not inhibit other groups of proteases, such as the neutral and alkaline proteases (1). The unusual potency of pepstatin toward acid prot
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Scytalidocarboxyl peptidase B, also known as Scytalidoglutamic peptidase and Scytalidopepsin B (EC 3.4.23.32, obsolete names include Scytalidium aspartic proteinase B, Ganoderma lucidum carboxyl proteinase, Ganoderma lucidum aspartic proteinase, Scytalidium lignicolum aspartic proteinase B, SLB) is a proteolytic enzyme. It was previously thought to be an aspartic protease, but determination of the its molecular structure showed it to belong a novel group of proteases, glutamic protease. The protease has a unique structure and a novel catalytic dyad (E136 and Q53) in its active site. The active-site residues, glutamic acid (E) and glutamine (Q), was used to coin the name of the family of proteases, eqolisins, to which Scytalidoglutamic peptidase B belongs. This enzyme catalyses the following chemical reaction Hydrolysis of proteins with broad specificity, cleaving Phe24-Phe and Tyr26-Thr but not Leu15-Tyr and Phe25-Tyr in the B chain of insulin. It also cleaves the His6-Pro bond of angiotensin I, ...
Gamma-secretase activity is vital for the transmembrane cleavage of Notch receptors and the subsequent migration of their intracellular domains to the nucleus. Notch overexpression has been associated with breast, colon, cervical and prostate cancers. We tested the effect of three different gamma-secretase inhibitors (GSIs) in breast cancer cells. One inhibitor (GSI1) was lethal to breast cancer cell lines at concentrations of 2 muM and above but had a minimal effect on the non-malignant breast lines. GSI1 was also cytotoxic for a wide variety of cancer cell lines in the NCI60 cell screen. GSI1 treatment resulted in a marked decrease in gamma-secretase activity and downregulation of the Notch signalling pathway with no effects on expression of the gamma-secretase components or ligands. Flow cytometric and western blot analyses indicated that GSI1 induces a G2/M arrest leading to apoptosis, through downregulation of Bcl-2, Bax and Bcl-XL. GSI1 also inhibited proteasome activity. Thus, the ...
The amyloid precursor protein gene (APP) and its derivative peptides have important functions in the central nervous system. APP and Aβ fulfil criteria as neuractive peptides: presence, release and identity of action. Aβ is a peptide of 1 - 43 amino acids in length, derived from APP and the major component of the core of neuritic plaques found in Alzheimers disease. Analysis of the cDNA of Aβ revealed its origins from the larger precursor protein. There are at least four types of mRNA generated by alternative splicing of exons 7 and 8. Exon 7 encodes a 57 amino acid sequence found in the extracellular domain with major homology to the Kunitz-type of serine protease inhibitors. APP is cleaved by three secretases known as α, β, and γ secretase which act on APP at different sites producing various fragments of differing amino acid length. The γ secretase is a macromolecular enzyme complex composed of presenilin 1, 2 and other molecular constitutents essential for its function.
Alzheimer`s disease is the most common cause of progressive cognitive decline in the aged population. Pathologically Alzheimer`s disease is characterized by the invariant accumulation of senile plaques. Senile plaques are predominantly composed of the amyloid beta-peptide (A-beta), which is derived from the membrane bound beta-amyloid precursor protein (beta-APP) by sequential proteolytic cleavage. The recently identified beta-secretase (BACE) is responsible for the cleavage at the N-terminus of the A-beta domain. This cleavage generates membrane-bound beta-APP-Cterminal fragments (beta-APP-CTF) which are the immediate precursor for gamma-secretase cleavage and therefore for liberation of A-beta. The present work shows that BACE moves along the secretory pathway, while it undergoes post-translational modifications, which can be monitored by a significant increase in the molecular mass and cleavage of its pro-peptide. BACE becomes N-glycosylated within the ER and the increase in molecular mass is ...
Alzheimer`s disease is the most common cause of progressive cognitive decline in the aged population. Pathologically Alzheimer`s disease is characterized by the invariant accumulation of senile plaques. Senile plaques are predominantly composed of the amyloid beta-peptide (A-beta), which is derived from the membrane bound beta-amyloid precursor protein (beta-APP) by sequential proteolytic cleavage. The recently identified beta-secretase (BACE) is responsible for the cleavage at the N-terminus of the A-beta domain. This cleavage generates membrane-bound beta-APP-Cterminal fragments (beta-APP-CTF) which are the immediate precursor for gamma-secretase cleavage and therefore for liberation of A-beta. The present work shows that BACE moves along the secretory pathway, while it undergoes post-translational modifications, which can be monitored by a significant increase in the molecular mass and cleavage of its pro-peptide. BACE becomes N-glycosylated within the ER and the increase in molecular mass is ...
Reducing production of amyloid-β (Aβ) peptide by direct inhibition of the enzymes that process amyloid precursor protein (APP) is a central therapeutic strategy for treating Alzheimers disease. However, small-molecule inhibitors of the β-secretase (BACE1) and γ-secretase APP processing enzymes have shown a lack of target selectivity and poor penetrance of the blood-brain barrier (BBB). Here, we have developed a high-affinity, phage-derived human antibody that targets BACE1 (anti-BACE1) and is anti-amyloidogenic. Anti-BACE1 reduces endogenous BACE1 activity and Aβ production in human cell lines expressing APP and in cultured primary neurons. Anti-BACE1 is highly selective and does not inhibit the related enzymes BACE2 or cathepsin D. Competitive binding assays and x-ray crystallography indicate that anti-BACE1 binds noncompetitively to an exosite on BACE1 and not to the catalytic site. Systemic dosing of mice and nonhuman primates with anti-BACE1 resulted in sustained reductions in ...
AICD, the C-terminal tail generated from the proteolytic cleavage of the Amyloid Precursor Protein (APP), has been generating interest for its transcriptional modulatory roles. AICD has been hypothesized to have such a function as it is generated by a gamma-secretase-mediated regulated intramembrane proteolysis step, analogous to the generation of Notch intracellular domain (NICD), a well-known transcriptional regulator, from Notch. The AICD/Fe65/Tip60 ternary complex has been proposed as the working transcriptional regulatory complex and some of its target genes have been reported. However, our knowledge of the functions of AICD is still limited due to difficulties in detecting and manipulating the rapidly degraded peptide. Looking at AICD transcription modulation targets from a genome-wide perspective will aid our understanding of the role of AICD tremendously. To this end, AICD chromatin binding sites were investigated from a genome-wide perspective by performing Chromatin Immunoprecipitation ...
Beta-amyloid production results from cleavage in the extracellular domain of APP by the beta-secretase (BACE1) , which results in the production of the APP C-terminal fragment C99. This fragment is further cleaved by the gamma-secretase at residues 40-42 to produce beta-amyloid 40 and 42 peptides. Beta-amyloid aggregation and neuritic plaque formation are pathologic hallmarks of Alzheimer disease. This peptide corresponds to the human beta-amyloid 1-40 peptide ...
A new study will look at the relationship between dementia and high blood pressure, and how blood flow is regulated in the brain. The findings may help researchers identify if some drugs already used for other human conditions may be useful for the treatment of diseases such as stroke and Alzheimers disease (AD). Academics at Bristol Universitys Dementia Research Group, based at Frenchay Hospital, have been awarded a grant of over £266,000 from the British Heart Foundation (BHF) to assess whether drugs that block a small naturally produced molecule called endothelin-1 can improve blood flow through the brain.. In animal models of AD a reduction in blood flow occurs well before the onset of Alzheimer-like damaging changes to brain tissue. The most potent cause of the narrowing of blood vessels is a small molecule called endothelin-1 (ET-1). This molecule is produced by the action of endothelin-converting enzymes (ECEs).. The Bristol-based academics recently found that ECE-2 in the brain of AD ...
It is clear that intramembrane proteolysis regulates many biological processes. As with other intramembrane proteases such as γ‐secretase/presenilin and SPP (Martoglio and Golde, 2003; Selkoe and Schenk, 2003), rhomboids may turn out to be useful therapeutic targets (Opitz et al, 2002; Urban and Freeman, 2003). The lack of an in vitro assay for rhomboid activity has been a limiting factor in the biochemical analysis of their proteolytic mechanisms. We have now demonstrated rhomboid activity both in detergent‐solubilised membrane extracts and in a highly purified fraction. These two versions of the in vitro assay have different utilities. The activity of multiple rhomboids can be rapidly determined in TX100 membrane extracts; and in purified fractions, precise quantification of relative activities can be measured. Here we have exploited both approaches to show that diverse rhomboids have differential activities on three model substrates, and to compare the activities of a number of purified ...
Amyloid-β-protein (Aβ), the key component of senile plaques in Alzheimers disease (AD) brain, is produced from amyloid precursor protein (APP) by cleavage of β-secretase and then γ-secretase. APP adaptor proteins with phosphotyrosine-binding (PTB) domains, including Dab (gene: DAB) and Numb (gene: NUMB), can bind to and interact with the conserved YENPTY-motif in the APP C-terminus. Here we describe, for the first time, the effects of RNAi knock-down of Dab and Numb expression on APP processing and Aβ production. RNAi knock-down of Dab and Numb in H4 human neuroglioma cells stably transfected to express either FL-APP (H4-FL-APP cells) or APP-C99 (H4-APP-C99 cells) increased levels of APP-C-terminal fragments (APP-CTFs) and lowered Aβ levels in both cell lines by inhibiting γ-secretase cleavage of APP. Finally, RNAi knock-down of APP also reduced levels of Numb in H4-APP cells. These findings suggest that pharmacologically blocking interaction of APP with Dab and Numb may provide novel
This gene encodes a member of the M13 family of endopeptidases. Members of this family are zinc-containing type II integral-membrane proteins that are important regulators of neuropeptide and peptide hormone activity. Mutations in this gene are associated with autosomal recessive distal arthrogryposis, type 5D. This gene has multiple pseudogenes on chromosome 2. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Mar 2014 ...
Today, the demand for speed in drug discovery is constantly increasing, particularly in the iterative processes of hit validation and expansion and lead optimization. Irradiation with microwaves (MWs) has been applied in the area of organic synthesis to accelerate chemical reactions and to facilitate the generation of new chemical entities since 1986. In the work presented in this thesis, the use of MW-mediated heating has been expanded to address three fields of drug discovery, namely hit expansion, chemical library generation and genomics.. In the first project, potential inhibitors of malaria aspartic proteases were designed and synthesized, partly by MW-assisted organic chemistry, and evaluated with regard to their inhibitory efficacy on five malaria aspartic proteases and their selectivity over two human aspartic proteases. The synthetic work included the development of fast and convenient methods of MW-assisted formation of thiazolidines and epoxy esters. Some of the resulting structures ...
Fig. 3. Dictyostelium has PS-dependent γ-secretase activity that processes human APP to release Aβ peptides. (A) Diagrams of human APP α, β and γ proteolytic cleavage sites, and processed fragments; shown are FL (full-length), ΔN (N-terminal deletion), α- and β-CTFs, Aβ40 peptide, and AICD regions. (B) Media conditioned by growing WT and ps1-null cells that express ΔN-APP (a truncated human APP) were analyzed for levels of Aβ40 and Aβ42 peptides by quantitative ELISA. Fresh media and media conditioned by native WT cells were used as negative controls. Bars indicate standard errors that are derived from two independent experiments, each with two replicates. (C)Protein samples were collected from growing native WT Dictyostelium, or WT and ps1-null Dictyostelium that express ΔN-APP. ΔN-APP expression and processed fragments (arrows) were determined by immunoblot assay using α-APP C-terminus. (D) Protein samples were collected from native and APP-expressing CHO cells untreated or ...
Looking for online definition of 1-Aspartic Acid in the Medical Dictionary? 1-Aspartic Acid explanation free. What is 1-Aspartic Acid? Meaning of 1-Aspartic Acid medical term. What does 1-Aspartic Acid mean?
Amyloid Precursor Protein Secretases: Endopeptidases that are specific for AMYLOID PROTEIN PRECURSOR. Three secretase subtypes referred to as alpha, beta, and gamma have been identified based upon the region of amyloid protein precursor they cleave.
TY - JOUR. T1 - HIV Protease Inhibitors Alter Amyloid Precursor Protein Processing via β-Site Amyloid Precursor Protein Cleaving Enzyme-1 Translational Up-Regulation. AU - Gannon, Patrick J.. AU - Akay-Espinoza, Cagla. AU - Yee, Alan C.. AU - Briand, Lisa A.. AU - Erickson, Michelle A.. AU - Gelman, Benjamin B.. AU - Gao, Yan. AU - Haughey, Norman J.. AU - Zink, M. Christine. AU - Clements, Janice E.. AU - Kim, Nicholas S.. AU - Van De Walle, Gabriel. AU - Jensen, Brigid K.. AU - Vassar, Robert. AU - Pierce, R. Christopher. AU - Gill, Alexander J.. AU - Kolson, Dennis L.. AU - Diehl, J. Alan. AU - Mankowski, Joseph L.. AU - Jordan-Sciutto, Kelly L.. PY - 2017/1/1. Y1 - 2017/1/1. N2 - Mounting evidence implicates antiretroviral (ARV) drugs as potential contributors to the persistence and evolution of clinical and pathological presentation of HIV-associated neurocognitive disorders in the post-ARV era. Based on their ability to induce endoplasmic reticulum (ER) stress in various cell types, we ...
The present study was designed to determine the effects of senescence and angiotensin II (Ang II) on expression and processing of amyloid precursor protein (APP) in human brain microvascular endothelial cells (BMECs). Senescence caused a decrease in APP expression thereby resulting in reduced secretion of soluble APPα (sAPPα). In contrast, β-site APP cleaving enzyme (BACE1) expression and production of amyloid β (Aβ)40 were increased in senescent endothelium. Importantly, in senescent human BMECs, treatment with BACE1 inhibitor IV inhibited Aβ generation and increased sAPPα production by enhancing a disintegrin and metalloprotease (ADAM)10 expression. Furthermore, Ang II impaired expression of ADAM10 and significantly reduced generation of sAPPα in senescent human BMECs. This inhibitory effect of Ang II was prevented by treatment with BACE1 inhibitor IV. Our results suggest that impairment of α-processing and shift to amyloidogenic pathway of APP contribute to endothelial dysfunction induced by
Accumulation of A beta peptide fragments of the APP protein and neurofibrillary tangles of the microtubule-associated protein tau are the cellular hallmarks of Alzheimers disease (AD). To investigate the relationship between APP metabolism and tau protein levels and phosphorylation, we studied human-stem-cell-derived forebrain neurons with genetic forms of AD, all of which increase the release of pathogenic A beta peptides. We identified marked increases in intracellular tau in genetic forms of AD that either mutated APP or increased its dosage, suggesting that APP metabolism is coupled to changes in tau proteostasis. Manipulating APP metabolism by beta-secretase and gamma-secretase inhibition, as well as gamma-secretase modulation, results in specific increases and decreases in tau protein levels. These data demonstrate that APP metabolism regulates tau proteostasis and suggest that the relationship between APP processing and tau is not mediated solely through extracellular A beta signaling to ...
TY - JOUR. T1 - Presenilin 1 mutations increase amyloid precursor protein production and proteolysis in Xenopus laevis oocytes. AU - Heyn, Sietske N.. AU - Vulliet, Philip R. PY - 2001/6/22. Y1 - 2001/6/22. N2 - Recent findings suggest that Presenilin 1 (PS1) mutations play a major role in the development of Alzheimers disease (AD) by increasing the production of the beta amyloid peptide (Aβ). The exact mechanism whereby mutations in PS1 lead to this effect is not clear. To examine the question of how PS1 might be involved in amyloid precursor protein (APP) processing, we constructed a chimera of human APP695 fused at the C-terminal to enhanced green fluorescent protein (EGFP). This construct was injected into Xenopus laevis oocytes in the presence of wild type PS1 or one of three PS1 mutations associated with AD. The cellular location of the APP695-EGFP construct was examined by fluorescent confocal microscopy. In addition, membrane fractions of oocytes expressing APP695-EGFP in the presence ...
1998). "Autocatalytic activation of human legumain at aspartic acid residues". FEBS Lett. 438 (1-2): 114-8. doi:10.1016/S0014- ... 1999). "An asparaginyl endopeptidase processes a microbial antigen for class II MHC presentation". Nature. 396 (6712): 695-9. ... 1998). "Cloning and expression of mouse legumain, a lysosomal endopeptidase". Biochem. J. 335 (Pt 1): 111-7. PMC 1219758 . PMID ... 2003). "Multistep autoactivation of asparaginyl endopeptidase in vitro and in vivo". J. Biol. Chem. 278 (40): 38980-90. doi: ...
... (EC 3.4.23.21, Rhizopus aspartic proteinase, neurase, Rhizopus acid protease, Rhizopus acid proteinase) is an ... A similar endopeptidase is found in R. niveus [2]. In peptidase family A1 (pepsin A family). Tsuru, D.; Hattori, A.; Tsuji, H ... Substrate specificity of acid protease of Rhizopus chinensis". Agric. Biol. Chem. 33: 1419-1426. doi:10.1080/00021369.1969. ... "Binding of a reduced peptide inhibitor to the aspartic proteinase from Rhizopus chinensis: implications for a mechanism of ...
Alternative names for this enzyme include Nepenthes acid proteinase and Nepenthes aspartic proteinase. Two isozymes have been ... The names cephalotusin, dionaeasin and droserasin have been proposed for similar aspartic endopeptidases originating from the ... 3. Acid proteases in the genus Nepenthes and Drosera peltata". J. Biochem. 72 (1): 73-81. PMID 5069751. Amagase S, Mori M, ... Aspartic proteinases: retroviral and cellular enzymes. New York: Plenum. pp. 453-458. ISBN 0-306-45809-8. Takahashi K, Tanji M ...
Candida albicans secretory acid proteinase, Candida olea acid proteinase, Candida aspartic proteinase, Candida olea aspartic ... Activates trypsinogen, and degrades keratin This endopeptidase js present in yeast Candida albicans. Remold, H.; Fasold, H.; ... This enzyme catalyses the following chemical reaction Preferential cleavage at the carboxyl of hydrophobic amino acids, but ... Candidapepsin (EC 3.4.23.24, Candida albicans aspartic proteinase, Candida albicans carboxyl proteinase, ...
Aspartic acid protease. *Metalloendopeptidase. *Threonine endopeptidase *Proteasome endopeptidase complex. *HslU-HslV peptidase ... The MEROPS online database for peptidases and their inhibitors: Aspartic Peptidases. *Aspartic+Endopeptidases at the US ... Aspartic endopeptidases EC 3.4.23. of vertebrate, fungal and retroviral origin have been characterised.[1] More recently, ... Many eukaryotic aspartic endopeptidases (MEROPS peptidase family A1) are synthesised with signal and propeptides. The animal ...
Capsid assembly in a family of animal viruses primes an autoproteolytic maturation that depends on a single aspartic acid ... Nodavirus endopeptidase (EC 3.4.23.44, Black Beetle virus endopeptidase, Flock House virus endopeptidase) is an enzyme. This ... Nodavirus endopeptidase at the US National Library of Medicine Medical Subject Headings (MeSH) Molecular and Cellular Biology ... Johnson, J.E.; Schneemann, A. (1998). "Nodavirus endopeptidase". In Barrett, A.J.; Rawlings, N.D.; Woessner, J.F. Handbook of ...
... especially glutamic acid, and to some extent aspartic acid. Glutamyl endopeptidase has been shown to cleave certain target ... Glutamyl endopeptidase is in S. aureus expressed from the gene sspA within the operon ssp. Downstream of sspA, the operon also ... Glutamyl endopeptidase is expressed as a zymogen that, in order to become fully active, has been modified both through ... Glutamyl endopeptidase can inhibit the activation of targets within the complement system. It is indicated to cause inhibition ...
Proteases of this group hydrolyzes peptide bonds after the negatively charged glutamic acid or aspartic acid, with a higher ... subtilis glutamyl endopeptidase GluBS Enterococcus E. faecalis glutamyl endopeptidase SprE Glutamyl endopeptidase is in at ... S. epidermidis glutamyl endopeptidase GluSE Also called S. epidermidis serine protease (Esp). S. warneri glutamyl endopeptidase ... Glutamyl endopeptidase I is a family of extracellular bacterial serine proteases. The proteases within this family have been ...
Aspartic endopeptidases EC 3.4.23. of vertebrate, fungal and retroviral origin have been characterised. More recently, aspartic ... Taylor RK, LaPointe CF (2000). "The type 4 prepilin peptidases comprise a novel family of aspartic acid proteases". J. Biol. ... The MEROPS online database for peptidases and their inhibitors: Aspartic Peptidases Aspartic Endopeptidases at the US National ... GPR endopeptidase family) Clan AF (e.g. Omptin family) Many eukaryotic aspartic endopeptidases (MEROPS peptidase family A1) are ...
... aspartic; C, cysteine; G, glutamic acid; M, metallo; S, serine; T, threonine; and U, unknown. The serine, threonine and ... These endopeptidases include CAAX prenyl protease 1, which proteolytically removes the C-terminal three residues of ... The metal ion is held in place by amino acid ligands, usually three in number. The known metal ligands are His, Glu, Asp or Lys ... In the case of aspartic, glutamic and metallopeptidases, the nucleophile is an activated water molecule. In many instances the ...
Aspartic acid protease. *Metalloendopeptidase. *Threonine endopeptidase *Proteasome endopeptidase complex. *HslU-HslV peptidase ... Proteasome endopeptidase complex (EC 3.4.25.1, ingensin, macropain, multicatalytic endopeptidase complex, prosome, ... Proteasome+endopeptidase+complex at the US National Library of Medicine Medical Subject Headings (MeSH) ... Retrieved from "https://en.wikipedia.org/w/index.php?title=Proteasome_endopeptidase_complex&oldid=826116286" ...
Aspartic acid protease. *Metalloendopeptidase. *Threonine endopeptidase *Proteasome endopeptidase complex. *HslU-HslV peptidase ... serine-type endopeptidase activity. Cellular component. • lamellipodium membrane. • extracellular exosome. • lysosomal membrane ... 1x70: HUMAN DIPEPTIDYL PEPTIDASE IV IN COMPLEX WITH A BETA AMINO ACID INHIBITOR ... 2oph: Human dipeptidyl peptidase IV in complex with an alpha amino acid inhibitor ...
Aspartic acid protease. *Metalloendopeptidase. *Threonine endopeptidase *Proteasome endopeptidase complex. *HslU-HslV peptidase ... aspartic acid, metallo- and acid proteases) nucleophilic so that it can attack the peptide carboxyl group. One way to make a ... aspartic, and metallo proteases.[2] The threonine and glutamic-acid proteases were not described until 1995 and 2004 ... depending on the amino acid sequence of a protein, or completely break down a peptide to amino acids (unlimited proteolysis). ...
Aspartic acid protease. *Metalloendopeptidase. *Threonine endopeptidase *Proteasome endopeptidase complex. *HslU-HslV peptidase ... 1990). "Galactosialidosis: simultaneous deficiency of esterase, carboxy-terminal deamidase and acid carboxypeptidase activities ...
Aspartic acid protease. *Metalloendopeptidase. *Threonine endopeptidase *Proteasome endopeptidase complex. *HslU-HslV peptidase ... aspartic-type endopeptidase activity. Cellular component. • multivesicular body. • late endosome. • endoplasmic reticulum lumen ... BACE1 is an aspartic-acid protease important in the formation of myelin sheaths in peripheral nerve cells: in mice the ... BACE1 is distantly related to the pathogenic aspartic-acid protease plasmepsin, which is a potential target for future anti- ...
Aspartic acid protease. *Metalloendopeptidase. *Threonine endopeptidase *Proteasome endopeptidase complex. *HslU-HslV peptidase ...
Aspartic Acid -OOC-CH2- Oxaloacetate → Aspartic Acid (aminotransferase) Glutamic Acid -OOC-(CH2)2- α-ketoglutarate → Glutamic ... EndopeptidasesEdit. Endopeptidases are enzymes that add water to an internal peptide bond in a peptide chain and break that ... Amino Acid SynthesisEdit. Pathways that form each amino acid[4]. Amino Acid R-group‡ Pathway* ... The main amino acids involved are serine, histidine, and aspartic acid. They all play a role in cleaving the peptide bond. ...
Aspartic endopeptidases EC 3.4.23. of vertebrate, fungal and retroviral origin have been characterised. More recently, aspartic ... Taylor RK, LaPointe CF (2000). "The type 4 prepilin peptidases comprise a novel family of aspartic acid proteases". J. Biol. ... Structurally, aspartic endopeptidases are bilobal enzymes, each lobe contributing a catalytic Asp residue, with an extended ... Jarrell KF, Bardy SL (2003). "Cleavage of preflagellins by an aspartic acid signal peptidase is essential for flagellation in ...
The defining features of these enzymes are a unique catalytic triad, Ser/Glu/Asp, as well as the presence of an aspartic acid ... The proprotein-processing endopeptidases kexin, furin and related enzymes form a distinct subfamily known as the kexin ... Members of the kexin family, along with endopeptidases R, T and K from the yeast Tritirachium and cuticle-degrading peptidase ... Over 200 subtilases are presently known, more than 170 of which with their complete amino acid sequence. Subtilase is ...
The protein is rich in acidic residues: 30-36% are either aspartic or glutamic acid. OPN is a highly negatively charged, ... PHEX (phosphate-regulating gene with homologies to endopeptidases on the X chromosome) is one such enzyme, which extensively ... Contiguous stretches of high negative charge in OPN have been identified and named the polyAsp motif (poly-aspartic acid) and ... Kiefer MC, Bauer DM, Barr PJ (April 1989). "The cDNA and derived amino acid sequence for human osteopontin". Nucleic Acids Res ...
... aspartic acid, metallo- and acid proteases) nucleophilic so that it can attack the peptide carboxyl group. One way to make a ... endopeptidases, such as trypsin, chymotrypsin, pepsin, papain, elastase). Catalysis is achieved by one of two mechanisms: ... aspartic, and metallo proteases. The threonine and glutamic-acid proteases were not described until 1995 and 2004 respectively ... using a threonine secondary alcohol Aspartic proteases - using an aspartate carboxylic acid Glutamic proteases - using a ...
Ste24 endopeptidase EC 3.4.24.85: S2P endopeptidase EC 3.4.24.86: ADAM 17 endopeptidase EC 3.4.24.87: ADAMTS13 endopeptidase EC ... Lotus aspartic proteinase EC 3.4.23.14: Deleted entry: sorghum aspartic proteinase EC 3.4.23.15: renin EC 3.4.23.16: HIV-1 ... Rhizopus acid proteinase. Now EC 3.4.23.21, rhizopuspepsin EC 3.4.23.10: Endothia acid proteinase. Now EC 3.4.23.22, ... ADAM10 endopeptidase EC 3.4.24.82: ADAMTS-4 endopeptidase EC 3.4.24.83: anthrax lethal factor endopeptidase EC 3.4.24.84: ...
Another family of signal aspartic endopeptidases was found in bacteria. Bacteria produce a number of protein precursors that ... A nine amino acid-long cleavage fragment is then presented on HLA-E receptors and modulates the activity of natural killer ... Martoglio B, Golde TE (October 2003). "Intramembrane-cleaving aspartic proteases and disease: presenilins, signal peptide ... which differ from mature pilin by virtue of containing a 6-8 residue leader peptide consisting of charged amino acids. Mature ...
This endopeptidase is isolated from Scytalidium lignicolum. It is an acid protease, and is most active at pH 2.0 when casein is ... Scytalidium lignicolum aspartic proteinase B, SLB) is a proteolytic enzyme. It was previously thought to be an aspartic ... Eqolosins prefer bulky amino acid residues at the P1 site and small amino acid residues at the P1′ site. The substrate ... "Complete amino acid sequence of Scytalidium lignicolum acid protease B". J. Biochem. 95: 465-473. doi:10.1093/oxfordjournals. ...
Green TB, Ganesh O, Perry K, Smith L, Phylip LH, Logan TM, Hagen SJ, Dunn BM, Edison AS (April 2004). "IA3, an aspartic ... This family includes PinA, which inhibits the endopeptidase La. It binds to the La homotetramer but does not interfere with the ... Murai H, Hara S, Ikenaka T, Oda K, Murao S (January 1985). "Amino acid sequence of Streptomyces metallo-proteinase inhibitor ... The saccharopepsin inhibitor I34 is highly specific for the aspartic peptidase saccharopepsin. In the absence of saccharopepsin ...
Nucleic Acids Res 44, D343-D350". Dautin, N., Barnard, T. J., Anderson, D. E., and Bernstein, H. D. (2007) EMBO J. 26, 1942- ... Family N2: Includes tetraviruses endopeptidases. The known autolytic cleavage is from the C-terminus of the coat protein. The ... Asparagine Lyase Protein precursor Proteolysis Nucleophilic substitution Protease cysteine- serine- threonine- aspartic- ... Reddy, A., Schneemann, A. & Johnson, J.E. Nodavirus endopeptidase. In Handbook of Proteolytic Enzymes, 2 edn (Barrett, A.J., ...
Amino acid-derived. *Major excitatory/inhibitory systems: Glutamate system: Agmatine. *Aspartic acid (aspartate) ... role of aminopeptidases and endopeptidases". Peptides. 12 (5): 1119-25. doi:10.1016/0196-9781(91)90068-z. PMID 1800950.. ... response to retinoic acid. • positive regulation of renal sodium excretion. • regulation of receptor activity. • G-protein ... Hornig D (September 1975). "Distribution of ascorbic acid, metabolites and analogues in man and animals". Annals of the New ...
"Acid and non-acid reflux in patients with persistent symptoms despite acid suppressive therapy: a multicentre study using ... Pepsin is an endopeptidase that breaks down proteins into smaller peptides (that is, a protease). It is produced in the stomach ... Dunn BM (Nov 2001). "Overview of pepsin-like aspartic peptidases". Current Protocols in Protein Science. Chapter 21: Unit 21.3 ... Weak or non-acid reflux is correlated with reflux symptoms and mucosal injury.[18][19][20][21] Under non-acid conditions ( ...
Polyclonal Antibody Flow Cytometry Amino Acid Transport, Polyclonal Antibody Flow Cytometry Adherens Junction Dynamics ... Polyclonal Antibody Flow Cytometry Aspartic-Type Endopeptidase Activity, Polyclonal Antibody Flow Cytometry Apoptosis, ... Category listing: Polyclonal Antibody Flow Cytometry Aspartic-Type Endopeptidase Activity to Polyclonal Antibody Fatty Acid ... Polyclonal Antibody Flow Cytometry Aspartic-Type Endopeptidase Activity Polyclonal Antibody Flow Cytometry Aspartic-Type ...
Find out information about Aspartic endopeptidases. organic compound, one of the 20 amino acids amino acid , any one of a class ... of simple organic compounds containing carbon, hydrogen, oxygen, nitrogen, and... Explanation of Aspartic endopeptidases ... aspartic acid. (redirected from Aspartic endopeptidases). Also found in: Dictionary, Thesaurus, Medical. aspartic acid. (əspär` ... Aspartic acid is not essential to the human diet. It was discovered in protein in 1868.. aspartic acid. [ə′spärd·ik ′as·əd] ( ...
Aspartic Acid Endopeptidases/genetics. *Aspartic Acid Endopeptidases/metabolism. *Aspartic Acid Endopeptidases/physiology* ... The secreted aspartic proteinase of C. albicans was first described in 1965 and has proved to be a major factor in virulence. ... The role of Candida albicans secreted aspartic proteinase in the development of candidoses.. Hoegl L1, Ollert M, Korting HC. ... This enzyme belongs to the class of aspartic proteinases which includes pepsin and renin in humans. Although found in some ...
Aspartic Acid Endopeptidases / drug effects, metabolism, secretion. Candida albicans / drug effects*. Clusiaceae*. Magnetic ... Aspartic Acid Endopeptidases; EC 3.4.23.1/Pepsin A ... 15247137 - Effect of folic acid supplementation on the folate ... 4-dihydroxybenzoic acid (14). Compounds 2, 3, 12 and 13 showed inhibitory effects against Candida albicans secreted aspartic ... 17830317 - Abscisic acid induces formation of floating leaves in the heterophyllous aquatic angios.... 20183257 - Two new ...
Aspartic Acid Endopeptidases * Bace1 protein, mouse Grant support * G-0904/Parkinsons UK/United Kingdom ...
In particular, serine endopeptidases, cysteine endopeptidases, aspartic acid endopeptidases and/or metalloendopeptidases may be ... The amino acid sequence and/or the amino acid sequence that is at least 80% homologous with it, preferably at least 90%, refers ... This amino acid sequence may also include other amino acids of the hinge-loop region, as explained above. ... In a preferred embodiment, the amino acid sequences ID No. 1 or ID No. 2 or amino acid sequences that are at least 80% ...
... serine proteases or serine endopeptidases (newer name) are a class of peptidases (enzymes that cleave peptide bonds in ... Endopeptidase 3.4.21-24. Serine proteases - Cysteine protease - Aspartic acid protease - Metalloendopeptidases. ... and aspartic acid (Asp 102). Located very near one another near the heart of the enzyme, these three key amino acids each play ... Instead of having the hydrophobic pocket of the chymotrypsin, there exists an aspartic acid residue at the base of the pocket. ...
Aspartic Acid Endopeptidases. *Axin Protein. *Cyclin D1. *Cytosol. *Endopeptidases/metabolism. *Fibroblasts/cytology ...
Aspartic Acid Endopeptidases. Papers overview. Semantic Scholar uses AI to extract papers important to this topic. ... The cDNA encoding the precursor of an aspartic proteinase from the flowers of the cardoon, Cynara cardunculus, was expressed in ... Isolation and characterization of a cDNA from flowers of Cynara cardunculus encoding cyprosin (an aspartic proteinase) and its ... Substrate specificity and molecular modelling of aspartic proteinases (cyprosins) from flowers of Cynara cardunculus subsp. ...
MMP8 WITH MALONIC AND ASPARTIC ACID BASED INHIBITOR ... are a family of zinc endopeptidases, which have been implicated ... MMP8 WITH MALONIC AND ASPARTIC ACID BASED INHIBITOR. *DOI: 10.2210/pdb1A86/pdb ... Among the hydroxamic acids, malonic acid derivatives have been used as MMP inhibitors, although optimization of their ... Various classes of MMP inhibitors, including hydroxamic acids, phosphinic acids, and thiols, have been previously described ... ...
The available amino acid sequences of peptidases have been examined, and the enzymes have been allocated to evolutionary ... Aspartic Acid Endopeptidases / chemistry Actions. * Search in PubMed * Search in MeSH * Add to Search ... The S8 Serine, C1A Cysteine and A1 Aspartic Protease Families in Arabidopsis EP Beers et al. Phytochemistry 65 (1), 43-58. Jan ... The available amino acid sequences of peptidases have been examined, and the enzymes have been allocated to evolutionary ...
secretions) and Drosera peltata (ground-up leaves). Aspartic endopeptidases are probably present in many other plants, inclu ... Nepenthes aspartic proteinase; Nepenthes acid proteinase; nepenthacin; nepenthasin; aspartyl endopeptidase. Reaction. Similar ... secretions) and Drosera peltata (ground-up leaves). Aspartic endopeptidases are probably present in many other plants, ...
1998). "Autocatalytic activation of human legumain at aspartic acid residues". FEBS Lett. 438 (1-2): 114-8. doi:10.1016/S0014- ... 1999). "An asparaginyl endopeptidase processes a microbial antigen for class II MHC presentation". Nature. 396 (6712): 695-9. ... 1998). "Cloning and expression of mouse legumain, a lysosomal endopeptidase". Biochem. J. 335 (Pt 1): 111-7. PMC 1219758 . PMID ... 2003). "Multistep autoactivation of asparaginyl endopeptidase in vitro and in vivo". J. Biol. Chem. 278 (40): 38980-90. doi: ...
Rhizopuspepsin (EC 3.4.23.21, Rhizopus aspartic proteinase, neurase, Rhizopus acid protease, Rhizopus acid proteinase) is an ... A similar endopeptidase is found in R. niveus [2]. In peptidase family A1 (pepsin A family). Tsuru, D.; Hattori, A.; Tsuji, H ... Substrate specificity of acid protease of Rhizopus chinensis". Agric. Biol. Chem. 33: 1419-1426. doi:10.1080/00021369.1969. ... "Binding of a reduced peptide inhibitor to the aspartic proteinase from Rhizopus chinensis: implications for a mechanism of ...
Aspartic Acid Endopeptidases/metabolism. *Biological Transport. *Carrier Proteins/genetics/metabolism. *Cell Membrane/ ...
Aspartic acid proteases, commonly known as acidic proteases, are the endopeptidases that depend on aspartic acid residues for ... Acid protease. Wheat bran. (Merheb-Dini et al., 2010). Thermomyces lanuginosus. SmF. 6.0. 50 °C. 0.71. -. Glucose, citric acid ... Acid protease. Czapek-Dox, peptone. (Larsen et al., 1998). Phanerochaete chrysosporium. SSF. 4.5. 25 °C. 35. Acid and ... based on the nature of the amino acid residues at the active site of the enzymes. Endopeptidases are characterized by their ...
... usually asparagine or aspartic acid, to orientate and activate the imidazolium ring. In only one family of cysteine peptidases ... Structural basis of murein peptide specificity of a gamma-D-glutamyl-l-diamino acid endopeptidase.. Structure 17 303-13 2009 ... Endopeptidases from cyanobacteria Anabaena variabilis and Nostoc punctiforme contains two major domains: a bacterial SH3-like ... They are inhibited by thiol chelators such as iodoacetate, iodoacetic acid, N-ethylmaleimide or p-chloromercuribenzoate. ...
Other names: Rhizopus aspartic proteinase; neurase; Rhizopus acid protease; Rhizopus acid proteinase. Comments: From the ... A similar endopeptidase is found in R. niveus [2]. In peptidase family A1 (pepsin A family). Formerly EC 3.4.23.9, and included ... Substrate specificity of acid protease of Rhizopus chinensis. Agric. Biol. Chem. 33 (1969) 1419-1426. 2. Kurono, Y., Chidimatsu ... 4. Suguna, K., Padlan, E.A., Smith, C.W., Carlson, W.D. and Davies, D.R. Binding of a reduced peptide inhibitor to the aspartic ...
Aspartic Acid Endopeptidases, cerebrospinal fluid, Female, Humans, Lupus Erythematosus, Systemic, metabolism, Male, Middle Aged ...
Aspartic Acid Endopeptidases. 1. + +. 252. Receptors, Endothelin. 1. + +. 253. Calcitonin Gene-Related Peptide. 1. + +. ... 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid. 1. + +. ...
Our finding that only PTP (not PC1/3, PC2, or the aspartic proteinase) possesses the ability to convert pro-NPY to NPY suggests ... Adrenal medulla; Adrenal Medulla/enzymology; Amino acid sequence; Animals; Aspartic acid; Aspartic Acid Endopeptidases/ ... Our finding that only PTP (not PC1/3, PC2, or the aspartic proteinase) possesses the ability to convert pro-NPY to NPY suggests ... Endopeptidases; Enkephalins; Enkephalins/metabolism; Enzymology; Furin; Humans; Men; Models; Biological; Molecular Sequence ...
Keywords: Aspartic Acid Endopeptidases - genetics, Amyloid beta-Peptides - metabolism, Amyloid Precursor Protein Secretases, ... Alzheimer Disease - prevention & control, Cell Line, Tumor, Endopeptidases - genetics, Gene Expression Regulation, Enzymologic ...
Chemical-registry-number] 0 / Oligopeptides; 0 / Protease Inhibitors; EC 3.4.23.- / Aspartic Acid Endopeptidases; EC 3.4.23 ... Nucleic Acid, Nucleoside, or Nucleotide. A1.4.1.2.1.6. Organophosphorus Compound. A1.4.1.2.1.7. Amino Acid, Peptide, or Protein ... Amino Acid Sequence. Humans. Models, Molecular. Molecular Sequence Data. Sequence Homology, Amino Acid ... A2.1.5.3.2. Amino Acid Sequence. A2.1.5.3.3. Carbohydrate Sequence. A2.1.5.4. Geographic Area. A2.2. Finding. A2.2.1. ...
Endopeptidases; EC 3.4.23.- / Aspartic Acid Endopeptidases; EC 3.4.23.46 / BACE1 protein, human; EC 3.4.23.46 / Bace1 protein, ... Aspartic Acid Endopeptidases. Bile Ducts / cytology. Cell Line, Transformed. Cholangitis, Sclerosing / metabolism. Cholangitis ... Nucleic Acid, Nucleoside, or Nucleotide. A1.4.1.2.1.6. Organophosphorus Compound. A1.4.1.2.1.7. Amino Acid, Peptide, or Protein ... A2.1.5.3.2. Amino Acid Sequence. A2.1.5.3.3. Carbohydrate Sequence. A2.1.5.4. Geographic Area. A2.2. Finding. A2.2.1. ...
... allowing for cleavage N-terminal to proline and between aspartic acid and proline (18). Carbamidomethylcysteine was set as a ... Achromobacter lyticus lysyl endopeptidase, and human keratins; a total of 52,355 forward entries) and concatenated with ... For the SILAC technology, cells are grown in the presence of light or heavy forms of amino acids, such as arginine and lysine. ... Rogers, M. B., Hosler, B. A., and Gudas, L. J. (1991) Specific expression of a retinoic acid-regulated, zinc-finger gene, Rex-1 ...
  • In modern-day enzymes, although the three-dimensional structures are very similar, the amino acid sequences are more divergent, except for the catalytic site motif, which is very conserved. (wikipedia.org)
  • Structure of malonic acid-based inhibitors bound to human neutrophil collagenase. (rcsb.org)
  • Among the hydroxamic acids, malonic acid derivatives have been used as MMP inhibitors, although optimization of their inhibition potency was not successful. (rcsb.org)
  • Here we report the design of malonic acid-based inhibitors using the X-ray structure of a collagenase/inhibitor complex, which revealed a nonsubstrate-like binding mode. (rcsb.org)
  • The observation of nonsubstrate-like binding confirms the original strategy for structure-based modeling of improved malonic acid inhibitors, and explains kinetic data that are inconsistent with substrate-like binding. (rcsb.org)
  • AmpC overproduction may occur through reversible induction of ampC expression during exposure to certain β-lactams (cephamycins and carbapenems) and β-lactamase inhibitors (clavulanic acid). (biomedcentral.com)
  • Acidic amino acids: Those whose side chains can carry a negative charge at certain ph values. (docplayer.net)
  • Acid phosphatases are localized in acidic lysosomes, and alkaline phosphatases are active in more basic cellular environments. (thermofisher.com)
  • One aspartate activates the water by abstracting a proton, enabling the water to perform a nucleophilic attack on the carbonyl carbon of the substrate scissile bond , generating a tetrahedral oxyanion intermediate stabilized by hydrogen-bonding with the second aspartic acid. (wikipedia.org)
  • The results showed a decrease in the relative quantity of dimeric, trimeric and anhydrous units, and a smaller reduction in monomer disaccharide pentapeptide (M5) levels, validating the occurrence of D,D-carboxypeptidase and D,D-endopeptidase activities. (biomedcentral.com)
  • In enzyme science, Acid Anhydride Hydrolases are a class of hydrolase enzyme reactions that catalyze the hydrolysis of a acid anhydride bond. (wellnessadvocate.com)
  • PepO has significant sequence identity to mammalian metallopeptidases, including endothelin-converting enzyme, which converts a potent vasoconstrictor into its active form, and neutral endopeptidase (NEP), which is involved in terminating the activity of opioid peptides. (asm.org)
  • These results indicate that FW213 pepO encodes an enzyme with activity similar to that of known mammalian endopeptidases. (asm.org)
  • They are inhibited by thiol chelators such as iodoacetate, iodoacetic acid, N -ethylmaleimide or p -chloromercuribenzoate. (ebi.ac.uk)
  • 4 Specifically, integrin αvβ3 binds ECM ligands including vitronectin, fibrinogen, von Willebrand factor, and thrombospondin through amino acid sequences that contain the RGD sequence. (pubmedcentralcanada.ca)
  • A novel mutagenesis strategy identifies distantly spaced amino acid sequences that are required for the phosphorylation of both the oligosaccharides of procathepsin D by N-acetylglucosamine 1-phosphotransferase. (ox.ac.uk)
  • Matrix metalloproteinases (MMPs) are a family of zinc endopeptidases, which have been implicated in various disease processes. (rcsb.org)
  • 4 . The process according to claim 1 , wherein the one or more proteolytic enzymes comprise both endopeptidase and exopeptidase activity. (google.ch)
  • Cytochrome c can catalyze several reactions such as hydroxylation and aromatic oxidation, and shows peroxidase activity by oxidation of various electron donors such as 2,2-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid), 2-keto-4-thiomethyl butyric acid and 4-aminoantipyrine. (patents.com)