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
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Patent
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References
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Journal ArticleDOI
MOLSCRIPT: a program to produce both detailed and schematic plots of protein structures
TL;DR: The MOLSCRIPT program as discussed by the authors produces plots of protein structures using several different kinds of representations, including simple wire models, ball-and-stick models, CPK models and text labels.
Journal ArticleDOI
On the size of the active site in proteases. I. Papain.
Israel Schechter,Arieh Berger +1 more
Journal ArticleDOI
Novel regulators of bone formation: molecular clones and activities.
John M. Wozney,Vicki Rosen,Anthony J. Celeste,Lisa M. Mitsock,Matthew J. Whitters,Ronald W. Kriz,Rodney M. Hewick,Elizabeth A. Wang +7 more
TL;DR: Human complementary DNA clones corresponding to three polypeptides present in this BMP preparation have been isolated, and expression of the recombinant human proteins have been obtained, and each appears to be independently capable of inducing the formation of cartilage in vivo.
Journal ArticleDOI
Matrix metalloproteinases and their inhibitors in connective tissue remodeling.
TL;DR: Latency is overcome by physical, chemical, and enzymatic treatments that separate the cysteine residue from the zinc Expression of the metalloproteinases is switched on by a variety of agents acting through regulatory elements of the gene, particularly the AP‐1 binding site.
Journal ArticleDOI
Matrix Metalloproteinases: A Review
Henning Birkedal-Hansen,William G. I. Moore,M.K. Bodden,L.J. Windsor,B. Birkedal-Hansen,Arthur A. Decarlo,Jeffrey A. Engler +6 more
TL;DR: The present review discusses in detail the primary structures and the overlapping yet distinct substrate specificities of MMPs as well as the mode of activation of the unique MMP precursors.
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Astacins, serralysins, snake venom and matrix metalloproteinases exhibit identical zinc-binding environments (HEXXHXXGXXH and Met-turn) and topologies and should be grouped into a common family, the 'metzincins'
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