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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Matrix Metalloproteinases: From Molecular Mechanisms to Physiology, Pathophysiology, and Pharmacology
Luiz Gustavo de Almeida,Hayley Thode,Yekta Eslambolchi,Sameeksha Chopra,Daniel Young,Sean E. Gill,Laurent Devel,Antoine Dufour +7 more
TL;DR: This review aims to discuss MMPs in preclinical models and human pathologies, and discusses new biochemical tools to track their proteolytic activity in vivo and ex vivo, in addition to future pharmacological alternatives to inhibit their detrimental functions in diseases.
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Matrix metalloproteinases: from biology to therapeutic strategies in cardiovascular disease.
TL;DR: The future challenge for cardiovascular medicine is to appropriately shift the pendulum, not to the exclusion of MMPs, but to the recognition of the dynamic interaction that exists between myocyte and nonmyocyte populations, which clearly affect the pathogenesis of many acquired and genetic disorders.
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Novel Targets for Antiinflammatory and Antiarthritic Agents
TL;DR: The biological roles of these inflammatory mediators are clearly understood thus offering new targets for design of novel inhibitors for incurable inflammatory diseases, and an overview of the current nonsteroidal antiinflammatory agents are provided.
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Characterization and cloning of metallo-proteinase in the excretory/secretory products of the infective-stage larva of Trichinella spiralis
TL;DR: Inhibitor sensitivity assays showed that the excretory/secretory (E/S) products of the infective-stage larvae of Trichinella spiralis contained serine, metallo-, cysteine and aspartic proteinases.
Journal ArticleDOI
The canonical methionine 392 of matrix metalloproteinase 2 (gelatinase A) is not required for catalytic efficiency or structural integrity: probing the role of the methionine-turn in the metzincin metalloprotease superfamily.
TL;DR: The results challenge the dogma that this methionine residue and the Met-turn, which are absolutely conserved in all of the subfamilies of the metzincins, play an essential role in catalysis or active site structure.
References
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