Huntington J A, Li W
Department of Haematology, Cambridge Institute for Medical Research, University of Cambridge, Wellcome Trust/MRC Building, Cambridge CB2 0XY, United Kingdom.
Cell Mol Life Sci. 2009 Jan;66(1):113-21. doi: 10.1007/s00018-008-8371-0.
Protein C inhibitor (PCI) is a widely distributed, multifunctional member of the serpin family of protease inhibitors, and has been implicated in several physiological processes and disease states. Its inhibitory activity and specificity are regulated by binding to cofactors such as heparin, thrombomodulin and phospholipids, and it also appears to have non-inhibitory functions related to hormone and lipid binding. Just how the highly conserved serpin architecture can support the multiple diverse functions of PCI is a riddle best addressed by protein crystallography. Over the last few years we have solved the structure of PCI in its native, cleaved and protein-complexed states. They reveal a conserved serpin fold and general mechanism of protease inhibition, but with some unique features relating to inhibitory specificity/promiscuity, cofactor binding and hydrophobic ligand transport.
蛋白C抑制剂（PCI）是丝氨酸蛋白酶抑制剂家族中一种广泛分布的多功能成员，与多种生理过程和疾病状态有关。其抑制活性和特异性通过与肝素、血栓调节蛋白和磷脂等辅因子结合来调节，并且它似乎还具有与激素和脂质结合相关的非抑制功能。高度保守的丝氨酸蛋白酶抑制剂结构如何支持PCI的多种不同功能，这是一个最好通过蛋白质晶体学来解决的谜题。在过去几年中，我们已经解析了处于天然、裂解和蛋白质复合状态的PCI的结构。这些结构揭示了保守的丝氨酸蛋白酶抑制剂折叠和蛋白酶抑制的一般机制，但在抑制特异性/混杂性、辅因子结合和疏水配体转运方面具有一些独特特征。
