Bergeron F, Leduc R, Day R
Département de Pharmacologie, Institut de Pharmacologie de Sherbrooke, Université de Sherbrooke, 3001, 12e Avenue Nord Sherbrooke, Québec, Canada J1H 5N4.
J Mol Endocrinol. 2000 Feb;24(1):1-22. doi: 10.1677/jme.0.0240001.
Limited proteolysis of most large protein precursors is carried out in vivo by the subtilisin-like pro-protein convertases. Many important biological processes such as peptide hormone synthesis, viral protein processing and receptor maturation involve proteolytic processing by these enzymes, making them potential targets for the development of novel therapeutic agents. However, the efficient development of such molecules requires a better understanding of the molecular mechanisms of proteolytic protein processing. Herein, we review the most recent findings on the molecular aspects of subtilisin-like convertase activity, such as the structural analysis of the proteases, the mechanisms of enzyme/substrate specificity, their interaction with other proteins such as 7B2, and the comparative tissue and cellular distribution of the enzymes and their substrates. These data are then used as a background for the review of the known biological functions of subtilisin-like pro-protein convertases, the reported clinical cases involving proteolytic processing defects and, finally, the ongoing development of new therapeutic inhibitor molecules based on this knowledge.
大多数大型蛋白质前体的有限蛋白水解在体内由枯草杆菌蛋白酶样前体蛋白转化酶进行。许多重要的生物学过程，如肽激素合成、病毒蛋白加工和受体成熟，都涉及这些酶的蛋白水解加工，这使它们成为新型治疗药物开发的潜在靶点。然而，要高效开发此类分子，需要更好地理解蛋白水解加工的分子机制。在此，我们综述了关于枯草杆菌蛋白酶样转化酶活性分子方面的最新研究结果，例如蛋白酶的结构分析、酶/底物特异性机制、它们与其他蛋白质（如7B2）的相互作用，以及这些酶及其底物在组织和细胞中的分布比较。这些数据随后被用作背景，以综述枯草杆菌蛋白酶样前体蛋白转化酶的已知生物学功能、报道的涉及蛋白水解加工缺陷的临床病例，以及最后基于这些知识正在进行的新型治疗抑制剂分子的开发。
