Physiology and pathophysiology of matrix metalloproteases.
Physiology and pathophysiology of matrix metalloproteases.
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DOI：
10.1007/s00726-010-0689-x
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发表时间：
2011-07
期刊：
影响因子：
3.5
通讯作者：
Bischoff, R.
中科院分区：
文献类型：
--
作者：
Klein, T.;Bischoff, R.
基质金属蛋白酶（MMP）包括基于涉及通过Zn 2+离子活化活性位点结合的水分子的保守机制切割蛋白质底物的酶家族。尽管MMP的催化结构域在结构上高度相似，但在底物特异性、细胞和组织定位、膜结合和调节方面存在许多差异，这使得MMP成为具有多种生理功能的非常通用的酶家族，其中许多功能仍未完全理解。基本上，MMP家族的所有成员都与疾病发展有关，特别是与癌症转移、慢性炎症和随后的组织损伤以及神经系统疾病有关。这刺激了一系列研究MMP抑制剂作为治疗剂，以及测量MMP水平作为诊断或预后标志物。与大多数蛋白质家族一样，破译MMP的功能是困难的，因为它们可以修饰许多蛋白质。这些反应中哪些是生理学或病理生理学相关的通常不清楚，尽管对基因敲除动物、人类遗传学和表观遗传学的研究以及使用天然或合成抑制剂的生化研究在很大程度上提供了见解。在这篇综述中，我们将概述23个成员的人类MMP家族和描述的功能，疾病的联系和结构和机制的特点。MMPs可分为可溶性（包括基质溶素）和膜锚定种类。我们坚持“MMP命名法”，并在引言中为读者提供许多，通常是不同的，这个酶家族的名称。
Matrix metalloproteases (MMPs) comprise a family of enzymes that cleave protein substrates based on a conserved mechanism involving activation of an active site-bound water molecule by a Zn2+ ion. Although the catalytic domain of MMPs is structurally highly similar, there are many differences with respect to substrate specificity, cellular and tissue localization, membrane binding and regulation that make this a very versatile family of enzymes with a multitude of physiological functions, many of which are still not fully understood. Essentially, all members of the MMP family have been linked to disease development, notably to cancer metastasis, chronic inflammation and the ensuing tissue damage as well as to neurological disorders. This has stimulated a flurry of studies into MMP inhibitors as therapeutic agents, as well as into measuring MMP levels as diagnostic or prognostic markers. As with most protein families, deciphering the function(s) of MMPs is difficult, as they can modify many proteins. Which of these reactions are physiologically or pathophysiologically relevant is often not clear, although studies on knockout animals, human genetic and epigenetic, as well as biochemical studies using natural or synthetic inhibitors have provided insight to a great extent. In this review, we will give an overview of 23 members of the human MMP family and describe functions, linkages to disease and structural and mechanistic features. MMPs can be grouped into soluble (including matrilysins) and membrane-anchored species. We adhere to the ‘MMP nomenclature’ and provide the reader with reference to the many, often diverse, names for this enzyme family in the introduction.
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