The metzincins--topological and sequential relations between the astacins, adamalysins, serralysins, and matrixins (collagenases) define a superfamily of zinc-peptidases.
Walter Stöcker,Frank Grams,Ulrich Baumann,Peter Reinemer,F. X. Gomis-Rüth,David B. McKay,Wolfram Bode +6 more
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TLDR
The corresponding four distinct families of zinc peptidases, the astacins, the matrix metalloproteinases (matrixins, collagenases), the adamalysins/reprolysins (snake venom proteinases/reproductive tract proteins), and the serralysins appear to have originated by divergent evolution from a common ancestor and form a superfamily of proteolytic enzymes for which the designation “metzincins” has been proposed.Abstract:
The three-dimensional structures of the zinc endopeptidases human neutrophil collagenase, adamalysin II from rattle snake venom, alkaline proteinase from Pseudomonas aeruginosa, and astacin from crayfish are topologically similar, with respect to a five-stranded beta-sheet and three alpha-helices arranged in typical sequential order. The four proteins exhibit the characteristic consensus motif HEXXHXXGXXH, whose three histidine residues are involved in binding of the catalytically essential zinc ion. Moreover, they all share a conserved methionine residue beneath the active site metal as part of a superimposable "Met-turn." This structural relationship is supported by a sequence alignment performed on the basis of topological equivalence showing faint but distinct sequential similarity. The alkaline proteinase is about equally distant (26% sequence identity) to both human neutrophil collagenase and astacin and a little further away from adamalysin II (17% identity). The pairs astacin/adamalysin II, astacin/human neutrophil collagenase, and adamalysin II/human neutrophil collagenase exhibit sequence identities of 16%, 14%, and 13%, respectively. Therefore, the corresponding four distinct families of zinc peptidases, the astacins, the matrix metalloproteinases (matrixins, collagenases), the adamalysins/reprolysins (snake venom proteinases/reproductive tract proteins), and the serralysins (large bacterial proteases from Serratia, Erwinia, and Pseudomonas) appear to have originated by divergent evolution from a common ancestor and form a superfamily of proteolytic enzymes for which the designation "metzincins" has been proposed. There is also a faint but significant structural relationship of the metzincins to the thermolysin-like enzymes, which share the truncated zinc-binding motif HEXXH and, moreover, similar topologies in their N-terminal domains.read more
Citations
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BJ46a, a snake venom metalloproteinase inhibitor. Isolation, characterization, cloning and insights into its mechanism of action.
TL;DR: This is the first report of a complete cDNA sequence for an endogenous inhibitor of snake venom metalloproteinases (SVMPs) and reveals that the only proteolytic processing required to obtain the mature protein is the cleavage of the signal peptide.
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Isolation of Two Novel Metalloproteinase-Disintegrin (ADAM) cDNAs That Show Testis-Specific Gene Expression
TL;DR: An ancestral analysis of all known mammalian ADAMs indicates that the zinc-binding motif in the catalytic domain arose once in a common ancestor and was subsequently lost by those members lacking this motif.
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Structural characterizations of nonpeptidic thiadiazole inhibitors of matrix metalloproteinases reveal the basis for stromelysin selectivity
Barry C. Finzel,Eric T. Baldwin,G.L. Bryant Jr,G. F. Hess,J. W. Wilks,C. M. Trepod,John E. Mott,Vincent P. Marshall,G. L. Petzold,R. A. Poorman,T. J. O'Sullivan,Heinrich J. Schostarez,M. A. Mitchell +12 more
TL;DR: The binding of two 5‐substituted‐l,3,4‐thiadiazole‐2‐thione inhibitors to the matrix metalloproteinase stromelysin (MMP‐3) has been characterized by protein crystallography, revealing an inherent flexibility of the substrate binding region leading to speculation about a possible mechanism for modulation of stromelyin activity and selectivity.
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The metalloprotease ADAM17 in inflammation and cancer.
TL;DR: The importance of ADAM17 to understand the biology of IL-6 and TNFα and their role in inflammatory diseases is highlighted and the role ofADAM17 in the formation and progression of different tumor entities is discussed.
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