Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.24.11 (CD10)
 9,792 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The peptidoglycans from several Gram-negative and Gram-positive periodontal pathogens were isolated, purified, and characterized both morphologically and chemically. In addition, the effects of the mureolytic enzymes, lysozyme, M-1 N-acetyl-muramidase, and the AM-3 endopeptidase, on the peptidoglycans were examined. These enzymes were found to be highly effective in the degradation of the purified peptidoglycans; however, a Bacteroides capillus peptidoglycan-protein complex exhibited a greater resistance to these enzymes. Morphologically, the peptidoglycans consisted of large saccular sheets which, when viewed by scanning electron microscopy, contained numerous holes and tears. Chemically, the peptidoglycans consisted of muramic acid, glucosamine, alanine, glutamic acid, and meso-diaminopimelic acid (DAP). One Bacteroides species, Bacteroides gingivalis strain W, contained glycine and LL-DAP, suggestive of an indirectly cross-linked A3 gamma peptidoglycan.
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PMID:Isolation and characterization of the peptidoglycans from selected gram-positive and gram-negative periodontal pathogens. 398 14

Cells of Bacillus thuringiensis containing refractile spores autolyzed readily when suspended in buffer. The autolysate contained enzymes which lysed vegetative cell walls of the organism. Three enzymes were isolated from the autolysate, and each was purified approximately 30-fold. One enzyme, most active near pH 4.0, was found to be an N-acetylmuramidase. The other two enzymes exhibited pH optima at 8.5. One was stimulated by cobalt ions and the other was not. The cobalt-stimulated enzyme was shown to be an N-acetylmuramyl-l-alanine amidase. The cobalt insensitive enzyme exhibited both N-acetylmuramyl-l-alanine amidase and endopeptidase activity. The amidase activity may reflect incomplete separation of the cobalt-stimulated enzyme. The endopeptidase cleaved the peptide bond between l-alanine d-glutamic acid. A cell wall lytic endopeptidase with this specificity has not been previously reported. All three enzymes were extremely limited in the range of bacterial cell walls which they attacked. Except for cell walls of Micrococcus lysodeikticus, which were lysed by the muramidase, only cell walls of members of the genus Bacillus were attacked.
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PMID:Isolation and characterization of three autolytic enzymes associated with sporulation of Bacillus thuringiensis var. thuringiensis. 573

Autolysis of isolated cell walls of Staphylococcus aureus strain Copenhagen was accompanied by the release of 1 mole of N-terminal alanine per mole of glutamic acid. No other N-terminal amino acids and no C-terminal amino acids were released. These observations indicated that complete hydrolysis of N-acetylmuramyl-l-alanine linkages ("amidase" action) had occurred. This was confirmed by fractionation and analysis of the products. Hydrolysis of 4-O-beta-N-acetylglucosaminyl-N-acetylmuramic acid linkages also occurred to a variable extent; on one occasion, complete degradation to disaccharides and hexosamine-free polypeptides (with intact pentaglycine cross-bridges) occurred. In one other instance, hydrolysis within pentaglycine bridges also occurred. Analyses of intact cell walls indicated that, in vivo, glycine endopeptidase activity was negligible and amidase activity was low, but that endo-beta-N-acetylglucosaminidase hydrolysed about 8% of the N-acetylglucosaminyl-N-acetylmuramic acid linkages. Autolysis of isolated cell walls was too slow for the enzymes isolated with them to have significant action during this isolation. The possible functions of these autolytic activities are discussed.
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PMID:Mechanism of autolysis of isolated cell walls of Staphylococcus aureus. 577 31

Pteroylpolyglutamate hydrolase was isolated from rat intestinal mucosa and purified with the aid of affinity chromatography. The affinity ligand was poly-gamma-glutamic acid (Mr approximately 12,000) derived from Bacillus subtilis. The specific enzymatic activity was increased 2,000-fold over the 100,000 X g supernatant of the mucosal homogenate with a yield of 20%. Sephadex G-200 gel filtration yielded an estimated molecular mass of 80,000 daltons. The isoelectric point was pH 8.2. The pH optimum in acetate buffer containing 1 mM zinc was 4.5. The KM values for pteroylheptaglutamate and pteroyltriglutamate were 0.21 and 0.67 microM, respectively. Polyanionic compounds, poly-gamma-glutamic acid, dextran sulfate, and heparin were noncompetitive inhibitors. Studies of the time course of hydrolysis of synthetic [3H]pteroylheptaglutamate by three separate techniques demonstrated the appearance of [3H]pteroylmonoglutamate, synchronous with substrate cleavage. Intermediate pteroyloligoglutamates were not detected. An endopeptidase-like mode of hydrolysis was further established by identification of a hexaglutamyl peptide as the other reaction product.
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PMID:Isolation and characterization of pteroylpolyglutamate hydrolase from rat intestinal mucosa. 654 36

The proteolytic specificity of hemorrhagic toxin a from the venom of Crotalus atrox (western diamondback rattlesnake) has been investigated by using the oxidized B chain of bovine insulin and other peptides as substrates. The toxin appears highly specific for X--Leu bonds (cleaving the His10--Leu11, Ala14--Leu15, and Tyr16--Leu17 bonds), with no detectable activity against the Gly--Phe, Phe--Phe, Phe--Tyr, and Leu--Tyr bonds also present in the insulin B chain. The X--Leu bond of the peptides Tyr-Gly-Gly-Phe-Leu, Phe-Ala-Leu, and Ala-Leu was also cleaved. The toxin seems to be a strict endopeptidase, in that the cleavage of the two most susceptible bonds, Ala14--Leu15 and Tyr16--Leu17, are mutually exclusive; i.e., cleavage of either bond results in the other being too close to either the amino- or carboxyl-terminal of its respective fragment for the enzyme to be effective against it. The X--Met bond of Tyr-Gly-Gly-Phe-Met was cleaved, although a dipeptide Gly-Met was not hydrolyzed after 16 h of incubation. The substrates not hydrolyzed are furylacryloylglycyl-L-leucinamide, carbobenzoxy-L-glutamylglycine, carbobenzoxyglycyl-L-glutamic acid, benzoyl-L-arginine-p-nitroanilide, L-lysine-p-nitroanilide, (L-Ala)3-p-nitroanilide, Gly-Met, Gly-Phe-Phe, Gly-Gly-Ala, TAME, and ATEE. The absence of hydrolytic activity against the last two substrates indicates that hemorrhagic toxin a does not possess trypsin- or chymotrypsin-like activity.
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PMID:Proteolytic specificity of hemorrhage toxin a isolated from western diamondback rattlesnake (Crotalus atrox) venom. 703 85

gamma-Glutamyl hydrolase is a ubiquitous enzyme that has the capacity to cleave gamma-glutamyl bonds of cellular folyl- and antifolylpoly-gamma-glutamates. This study has revealed that the enzyme is secreted by primary cultures of rat hepatocytes and by H35 hepatoma cells. It was found that more than 99% of the total enzyme from H35 cells accumulated in the medium after 48 hr incubation with the serum-free medium. The cells were shown to remain intact during the secretion period since lactate dehydrogenase, dihydrofolate reductase and lysosomal hydrolases other than gamma-glutamyl hydrolase were retained within the cell. When PteGlu5 (folylGlu4) is used as a substrate the initial product is PteGlu (folate), and there is no appearance of intermediate chain length pteroyl polyglutamates. Therefore, the secreted and cellular gamma-glutamyl hydrolase from hepatoma cells appears to be an endopeptidase. Polyclonal antibodies to the poly-gamma-glutamate substrates of the enzyme were prepared and characterized. The antibodies recognize the structural differences between alpha- and gamma-glutamyl linkages but appear equally active with PteGlu5 and its analogs such as 4-NH2-10-CH3PteGlu5 and pABAGlu5. The affinity of the antibodies is related to the gamma-glutamyl structure since L-glutamic acid, folate or p-aminobenzoic acid are inactive with the antibodies. Furthermore, poly-gamma-glutamate has lower affinity for the antibodies than the poly-gamma-glutamate derivatives of PteGlu, 4-NH2-10-CH3PteGlu or pABA.
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PMID:The properties and function of gamma-glutamyl hydrolase and poly-gamma-glutamate. 768 89

1. Adamalysin II, alias proteinase II, a 24-kDa zinc-endopeptidase from the snake venom of Crotalus adamanteus, is a member of a large family of metalloproteinases isolated as small proteinases or proteolytic domains of mosaic hemorrhagic proteins from various snake venoms. Homologous domains have been recently detected in multimodular mammalian reproductive tract proteins and in mammalian gene products, somatic rearrangements of which seem to be linked to primary breast cancers. 2. The 2.0 A X-ray crystal structure of adamalysin II reveals an ellipsoidal molecule with a shallow active-site cleft separating a relatively irregularly folded sub-domain from the main molecular body composed of a 5-stranded beta-sheet and four alpha-helices. Opposite to this active-site cleft is an integrated calcium ion liganded by carbonyl and strongly conserved carboxylate/carboxamide residues. The folding of the peptide fragment containing the zinc-binding motif HExxHxxGxxH bears only a distant resemblance to thermolysin; it is identical to that found in astacin, in collagenases, and in serralysins, with the three histidines (His142, His146, His152) and a water molecule (linked to the glutamic acid Glu143) likewise constituting the zinc ligand; similar to collagenases, but in contrast to astacin, adamalysin II lacks a fifth (tyrosine) zinc ligand, leaving its zinc-ion tetrahedrally coordinated. Furthermore, adamalysin II shares an identical active-site basement formed by a common Met-turn. 3. Due to their virtually identical active-site environment and similar folding topology, the snake venom metalloproteinases (hitherto called adamalysins) and the three other proteinases might be grouped into a common superfamily called metzincins with distinct differences from the thermolysin family.
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PMID:The crystal structure of adamalysin II, a zinc-endopeptidase from the snake venom of the eastern diamondback rattlesnake Crotalus adamanteus. 774 94

The gamma-carboxylase recognition site in the propeptide of profactor IX signals the gamma-carboxylation of specific glutamic acid residues in the adjacent Gla domain during factor IX biosynthesis. To study posttranslational processing of the vitamin K-dependent blood coagulation factors and the properties of processing intermediates, we have isolated an incompletely processed factor IX species, profactor IX, from the medium of heterologous mammalian cells expressing the human factor IX cDNA. Profactor IX was purified by sequential immunoaffinity chromatography using antibodies specific for the propeptide and antibodies specific for the well-carboxylated factor IX species. This purified profactor IX preparation was fully gamma-carboxylated and contained the N-terminal propeptide, but it exhibited no factor IX procoagulant activity. Profactor IX was not cleaved following incubation with factor XIa. In contrast to mature factor IX, profactor IX did not demonstrate Ca(II)-dependent binding to acidic phospholipid vesicles, nor can the membrane binding surface be expressed, as detected by antibodies specific for this epitope. The propeptide of profactor IX can be removed in vitro by a specific endopeptidase, furin/PACE, yielding factor IX, which can be converted to fully active factor IXa by factor XIa and which binds normally to acidic phospholipid vesicles. These results indicate that fully gamma-carboxylated profactor IX is biologically inactive due to the presence of the propeptide.
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PMID:Profactor IX: the propeptide inhibits binding to membrane surfaces and activation by factor XIa. 794 25

A scheme based on the zinc binding site [1992, FEBS Lett. 312, 110-114] has been extended to classify zinc metalloproteases into distinct families. The gluzincins, defined by the HEXXH motif and a glutamic acid as the third zinc ligand, include the thermolysin, endopeptidase-24.11, aminopeptidase, angiotensin converting enzyme, endopeptidase-24.15, and tetanus and botulinum neurotoxin families. The metzincins, defined by the HEXXH motif, a histidine as the third zinc ligand and a Met-turn, include the astacin, serralysin, reprolysin and matrixin families. The inverted zincin motif, HXXEH, defines the inverzincin family of insulin-degrading enzymes, the HXXE motif defines the carboxypeptidase family, and the HXH motif DD-carboxypeptidase.
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PMID:Families of zinc metalloproteases. 795 88

Adamalysin II, alias proteinase II, a 24 kDa zinc-endopeptidase isolated from the snake venom of the Eastern diamondback rattlesnake Crotalus adamanteus, is a prototype of the proteolytic domain of snake venom metalloproteinases and of domains found in mammalian reproductive tract proteins. Its 2.0 A crystal and molecular structure was solved by multiple isomorphous replacement using six heavy-atom derivatives, and was refined to a crystallographic R-value of 0.172. 201 of the 203 amino acid residues of adamalysin II are defined by electron density; only the first two residues are disordered and crystallographically undefined in the crystal structure. Three-quarters of these crystallographic amino acid residue assignments were confirmed by chemical sequencing. In addition, the active-site zinc-ion, a hepta-coordinated calcium ion, a fixed sulphate anion and 173 solvent molecules were localized in the structure. Adamalysin II is an ellipsoidal molecule with a relatively flat active-site cleft separating the "upper" main body from a small "lower" subdomain. The regularly folded N-terminal upper domain consists essentially of a central, highly twisted five-stranded beta-pleated sheet flanked by a long and a short surface located helix on its convex side, and by two long helices, one of which represents the central "active site helix", on its concave side. The lower subdomain, comprising the last 50 residues, is organized in multiple turns, with the chain ending in a long C-terminal helix and an extended segment clamped to the upper domain via a disulphide bridge. The catalytic zinc-ion, located at the bottom of the active-site cleft, is almost tetrahedrally co-ordinated by His142, His146 and His152, and a water molecule anchored to an intermediate glutamic acid residue (Glu143), with the three imidazole N epsilon 2 nitrogen atoms 2.1 A and the solvent oxygen atom 2.4 A away from the zinc ion. His142, Glu143 and His146 are part of the long active-site helix, which extends up to Gly149, where it turns sharply away towards His152. The importance of these residues for structure and activity of adamalysin II explains their occurrence in the HEXXHXXGXXH consensus sequence. Asp153, which is strictly conserved in these snake venom and reproductive tract metalloproteinases, is buried in the subdomain and seems to stabilize the hydrophobic active-site basement. Some residues behind, the adamalysin peptide chain folds into a characteristic 1,4-turn (the "Met-turn") containing the conserved Met166, which forms a hydrophobic basement for the three zinc-binding imidazoles.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Refined 2.0 A X-ray crystal structure of the snake venom zinc-endopeptidase adamalysin II. Primary and tertiary structure determination, refinement, molecular structure and comparison with astacin, collagenase and thermolysin. 800 65


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