![]() Crystal structures of MMPs in complex with physiological and pharmacological inhibitors. Molecular determinants of metalloproteinase substrate specificity: matrix metalloproteinase substrate binding domains, modules, and exosites. The metzincins-topological and sequential relations between the astacins, adamalysins, serralysins, and matrixins (collagenases) define a superfamily of zinc-peptidases. 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'. Coordinate expression of matrix metalloproteinase family members in the uterus of normal, matrilysin-deficient, and stromelysin-1-deficient mice. Targeted deletion of matrix metalloproteinase-9 attenuates left ventricular enlargement and collagen accumulation after experimental myocardial infarction. ![]() Mutations in two matrix metalloproteinase genes, MMP-2 and MT1-MMP, are synthetic lethal in mice. Altered endochondral bone development in matrix metalloproteinase 13-deficient mice. A critical analysis of why MMP inhibitors failed as cancer therapeutics, despite great promise. Matrix metalloproteinase inhibitors and cancer: trials and tribulations. New functions for the matrix metalloproteinases in cancer progression. ![]() The collagen substrate specificity of rat uterus collagenase. Matrix metalloproteinases: a tail of a frog that became a prince. Collagenolytic activity in amphibian tissues: a tissue culture assay. melanogaster larval development, mammalian skeletal, vascular and mammary development and in inflammation and wound repair. We highlight the consequences of modifying MMP action in D. In this Review, we synthesize the current genetic evidence from mice, flies and humans on the normal functions of MMPs in embryonic and postnatal development. Each mutant is larval lethal with defects in tissue remodelling.Ĭollectively, the loss-of-function studies in different organisms point to MMPs as mediators of change and physical adaptation in tissues, whether developmentally regulated, environmentally induced or associated with disease.Īn important outstanding question is whether MMPs function primarily as structural effectors of tissue remodelling or as regulators of signalling networks. Mutations in mouse MMP genes have displayed phenotypes in normal skeletal, mammary and vascular development.ĭrosophila melanogaster has only two MMP genes mutations in both MMP genes have been isolated. Recent work has highlighted the diverse consequences of MMP proteolysis on normal and pathological cell behaviour. Matrix metalloproteinases (MMPs) were discovered because of their role in amphibian metamorphosis, yet they have attracted more attention because of their roles in disease.
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