Insights into MMP-TIMP interactions
Insights into MMP-TIMP interactions
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DOI：
10.1111/j.1749-6632.1999.tb07675.x
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发表时间：
1999-01-01
期刊：
影响因子：
--
通讯作者：
Maskos, K
中科院分区：
文献类型：
--
作者：
Bode, W;Fernandez-Catalan, C;Maskos, K
参与细胞外基质降解的基质金属蛋白酶（MMPs）的蛋白水解活性必须由其内源性蛋白抑制剂--金属蛋白酶组织抑制剂（TIMPs）精确调节。这种平衡的破坏可以导致严重的疾病，例如关节炎和肿瘤生长和转移。了解参与这种过程的蛋白质的三级结构对于理解它们的功能特性和干扰相关的功能障碍是至关重要的。在过去的几年中，已经确定了几种三维结构，显示了结构域组织，多肽折叠，和基质金属蛋白酶的主要特异性决定因素。催化MMP结构域与各种合成抑制剂的复合物使得基于结构的设计和高亲和力配体的改进成为可能，这些高亲和力配体可能被精细化成药物。最近，一些TIMP结构和MMP-TIMP复合物的结构信息也变得可用，并且这些新数据阐明了控制酶-抑制剂相互作用的重要结构特征。
The proteolytic activity of the matrix metalloproteinases (MMPs) involved in extracellular matrix degradation must be precisely regulated by their endogenous protein inhibitors, the tissue inhibitors of metalloproteinases (TIMPs). Disruption of this balance can result in serious diseases such as arthritis and tumor growth and metastasis, Knowledge of the tertiary structures of the proteins involved in such processes is crucial for understanding their functional properties and to interfere with associated dysfunctions, Within the last few years, several three-dimensional structures have been determined showing the domain organization, the polypeptide fold, and the main specificity determinants of the MMPs. Complexes of the catalytic MMP domains with various synthetic inhibitors enabled the structure-based design and improvement of high-affinity ligands, which might be elaborated into drugs, Very recently, structural information also became available for some TIMP structures and MMP-TIMP complexes, and these new data elucidated important structural features that govern the enzyme-inhibitor interaction.