Whisstock James C, Bottomley Stephen P, Bird Phillip I, Pike Robert N, Coughlin Paul
The Department of Biochemistry and Molecular Biology, Monash University Clayton Campus, Melbourne, Victoria, Australia.
FEBS J. 2005 Oct;272(19):4868-73. doi: 10.1111/j.1742-4658.2005.04927.x.
Serpins are the largest family of protease inhibitors and are fundamental for the control of proteolysis in multicellular eukaryotes. Most eukaryote serpins inhibit serine or cysteine proteases, however, noninhibitory members have been identified that perform diverse functions in processes such as hormone delivery and tumour metastasis. More recently inhibitory serpins have been identified in prokaryotes and unicellular eukaryotes, nevertheless, the precise molecular targets of these molecules remains to be identified. The serpin mechanism of protease inhibition is unusual and involves a major conformational rearrangement of the molecule concomitant with a distortion of the target protease. As a result of this requirement, serpins are susceptible to mutations that result in polymerization and conformational diseases such as the human serpinopathies. This review reports on recent major discoveries in the serpin field, based upon presentations made at the 4th International Symposium on Serpin Structure, Function and Biology (Cairns, Australia).
丝氨酸蛋白酶抑制剂是最大的蛋白酶抑制剂家族，对于多细胞真核生物中蛋白水解的控制至关重要。大多数真核生物丝氨酸蛋白酶抑制剂抑制丝氨酸或半胱氨酸蛋白酶，然而，已鉴定出在激素传递和肿瘤转移等过程中发挥多种功能的非抑制性成员。最近在原核生物和单细胞真核生物中也发现了抑制性丝氨酸蛋白酶抑制剂，不过，这些分子的确切分子靶点仍有待确定。丝氨酸蛋白酶抑制剂抑制蛋白酶的机制不同寻常，涉及分子的主要构象重排以及靶蛋白酶的变形。由于这一要求，丝氨酸蛋白酶抑制剂易受导致聚合和构象疾病（如人类丝氨酸蛋白酶抑制剂病）的突变影响。本综述基于在第四届丝氨酸蛋白酶抑制剂结构、功能与生物学国际研讨会（澳大利亚凯恩斯）上的报告，介绍了丝氨酸蛋白酶抑制剂领域的近期重大发现。
