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首页> 外文期刊>Biological chemistry >Structural Basis of the Matrix Metalloproteinases and Their Physiological Inhibitors, the Tissue Inhibitors of Metalloproteinases
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Structural Basis of the Matrix Metalloproteinases and Their Physiological Inhibitors, the Tissue Inhibitors of Metalloproteinases

机译:基质金属蛋白酶的结构基础及其生理抑制剂,金属蛋白酶的组织抑制剂

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摘要

The matrix metalloproteinases (MMPs) constitute a family of multidomain zinc endopeptidases with a metzincin-like catalytic domain, which are involved in extracellular matrix degradation but also in a number of other important biological processes. Under healthy conditions, their proteolytic activity is precisely regulated by their main endogenous protein inhibitors, the tissue inhibitors of metalloproteinases. Disruption of this balance results in pathophysiological processes such as arthritis, tumor growth and metastasis, rendering the MMPs attractive targets for inhibition therapy. Knowledge of their tertiary structures is crucial for a full understanding of their functional properties and for rational drug design. Since the first appearance of atomic MMP structures in 1994, a large amount of structural information has become available on the catalytic domains of MMPs and their substrate specificity, interaction with synthetic inhibitors and the TIMPs, the domain organization, and on complex formation with other proteins. This review will outline our current structural knowledge of the MMPs and the TIMPs.
机译:基质金属蛋白酶(MMP)构成了一个多域锌内肽酶家族,带有一个美赞辛样催化域,不仅参与细胞外基质降解,而且参与许多其他重要的生物学过程。在健康条件下,它们的蛋白水解活性受其主要的内源性蛋白质抑制剂(金属蛋白酶的组织抑制剂)精确调节。这种平衡的破坏导致诸如关节炎,肿瘤生长和转移的病理生理过程,使得MMP成为抑制疗法的有吸引力的靶标。了解其三级结构对于全面了解其功能特性和合理的药物设计至关重要。自1994年首次出现原子MMP结构以来,关于MMP的催化结构域及其底物特异性,与合成抑制剂和TIMP的相互作用,结构域组织以及与其他蛋白质的复合物形成的大量结构信息已变得可用。 。这篇综述将概述我们目前对MMP和TIMP的结构知识。

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