Crystal structures of MMPs in complex with physiological and pharmacological inhibitors

被引:167
作者
Maskos, K [1 ]
机构
[1] Max Planck Inst Biochem, Abt Strukturforsch, D-82152 Martinsried, Germany
关键词
metalloprotease; NIMP; collagenase; latency; dimerization; inhibition; structure;
D O I
10.1016/j.biochi.2004.11.019
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Matrix Metalloproteinases (MMPs) are a family of multidomain zinc endopeptidases that function in the extracellular space or attached to the cell membrane. Their proteolytic activity is controlled by the presence of endogenous inhibitors, the tissue inhibitors of matrix metalloproteinases (TIMPs), alpha-macroglobulin and others. Disruption of the proteinase-inhibitor balance is observed in serious diseases such as arthritis, tumor growth and metastasis, rendering the MMPs attractive targets for drug intervention by pharmacological inhibitors. The determination of MMP structures is of critical importance in order to understand their substrate preferences, dimerization events, and their association with matrix components and inhibitors. Thus, MMP structures may contribute significantly to the development of specific MMP inhibitors, which should allow precise control of individual members of the MMP family without affecting all members or the closely related metalloproteinases such as ADAMs and ADAMTSs. (c) 2005 Elsevier SAS. All rights reserved.
引用
收藏
页码:249 / 263
页数:15
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