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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Overexpression and mechanistic characterization of blastula protease 10, a metalloprotease involved in sea urchin embryogenesis and development.
TL;DR: These are the first thorough mechanistic studies reported on Blastula protease 10 as a representative of the more structurally complex members of astacin-type enzymes in deuterostomes, which can add supporting data to corroborate the metal-centered mechanism proposed for Astacin and the role of the coordinated Tyr.
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Molecular Modeling and Analysis of Fragilysin, the Bacteroides fragilis Toxin
TL;DR: The results from these studies together support the role of enterotoxigenic B. fragilis in gastrointestinal diseases in humans and animals and suggest that fragilysin may disrupt the epithelial paracellular barrier through proteolytic degradation.
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Effect of mutalysin II on vascular recanalization after thrombosis induction in the ear of the hairless mice model
Ubirajara Agero,Rosa Maria Esteves Arantes,Norinne Lacerda-Queiroz,Oscar N. Mesquita,Arinos Magalhães,Eladio F. Sanchez,Juliana Carvalho-Tavares +6 more
TL;DR: In vivo data suggest that Mutalysin II has the potential to be an effective thrombolytic agent in hairless mice.
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Inhibition of adamalysin II and MMPs by phosphonate analogues of snake venom peptides.
Silvana D'alessio,Carlo Gallina,Enrico Gavuzzo,Cesare Giordano,Barbara Gorini,Fernando Mazza,Mario Paglialunga Paradisi,Gabriella Panini,Giorgio Pochetti,Antonio Sella +9 more
TL;DR: Both the phosphonate and carboxylate peptidomimetics fit into the active site adopting a retrobinding mode and provide the structural base for a new class of metalloproteinases inhibitors.
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The astacin family of metalloproteinases
TL;DR: Special attention is paid to physiological functions of the astacin proteinases and to the influence of domain composition and posttranslational modifications on the activity and stability of these enzymes.
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