Matrix metalloproteinases family

Matrix Metalloproteinase family Human fibroblast collagenase ICGL HiSa 3 HiSa 5 His H2O ... 

Class III Hydrolase Matrix Metalloproteinase Family Human fibroblast collagenase (MMP-1) ICGL His 1 Asp 12 His/i 12 His/i... 

The matrix metalloproteinases are inhibited by specific endogenous tissue inhibitor of metalloproteinases (TIMPs), which comprise a family of four protease inhibitors TIMP-1, TIMP-2, TIMP-3, and TIMP-4. Overall, all MMPs are inhibited by TIMPs once they are activated but the gelatinases (MMP-2 and MMP-9) can form complexes with TIMPs when the enzymes are in the latent form. 

Bode W, Gomis-Ruth FX, Stocker W. Astacins, serralysins, snake venom and matrix metalloproteinases exhibit idential zinc-binding environments (HEXXHXXGXXH and Met-turn) and topologies and should be grouped into a common family, the metzincins. FEBS Lett 1993 331 134-140. 

In the normal healthy IVD, the cells not only produce matrix macromolecules and growth factors, they also produce a myriad of proteases [26, 27]. Included in this list of proteases are the matrix metalloproteinases (MMPs) and aggrecanolytic members of the disintegrin and metalloproteinase with thrombospondin motif family (ADAMTS) as well as their respective inhibitors. It is the maintenance of this critical balance that results in a healthy IVD ECM that is subsequently well adapted for its physiologic and biomechanical function. 

Hydroxamic acid derivatives, which belong to a new class of NO donors, have been shown to inhibit the matrix metalloproteinases (MMPs) [112]. MMPs are a family of zinc-dependent endopeptidases, which play a critical role in multiple steps in the metastatic cascade and facilitate neoangiogenesis. Numerous hydroxamic acids, such as marimastat, have been developed, that bind the zinc atom in the active catalytic domain of MMPs. During a randomized Phase III trial, comparing marimastat with placebo in patients with metastatic breast cancer, marimastat was not associated with an improvement in progression-free survival or overall survival. Other studies also indicated no benefit for MMP inhibitors when used either in combination with chemotherapy or sequentially after first-line chemotherapy in a variety of cancers [113]. Currently, many pharmaceutical companies have suspended clinical development of this kind of agent. 

ADAM. A Disintesrin And MetalloProteinase family of proteins. Disintegrins, as the name implies, are proteins which interfere with interactions of cells with proteins in the extracellular matrix. An example are the inhibitors of the interaction of blood platelets with fibrinogen. Disintegrins are found in snake venom. Metalloproteinases are a family of proteases which need a bivalent cation for catalysis. MMP s are matrix metallo-proteases. They are associated with the extracellular matrix. 

The matrix metalloproteinases (MMPs) are a large family of endopeptidases, responsible for degradation of a variety of extracellular matrix components in both normal tissue remodeling and pathological states [47]. The active site is a cavity spanning the entire enzyme, with three subsites on each side of the scissile bond (S3-S3, see Fig. 3.14). Most of the known MMP inhibitors so far exert their function by coordinating to residues in the primed side [48], only little effort has been put into exploring the unprimed sites [49, 50]. 

The metzincins contain several sub-families. Astacins, bacterial serralysins, matrix metalloproteinases (MMPs), ADAMs (a disintegrating and metalloproteinase),... 

The matrix metalloproteinases (MMPs) are a family of calcium- and/or zinc-dependent endopeptidases involved in degradation of extracellular matrix and tissue remodelling (7). At least 21 mammalian MMPs have been described. They participate in various biological processes, such as embryonic development, ovulation, angiogenesis, apoptosis, wound heahng, and nerve growth. 

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