Shen Aimee
Department of Pathology, Stanford School of Medicine, Stanford, California 94305, USA.
Mol Biosyst. 2010 Aug;6(8):1431-43. doi: 10.1039/c003913f. Epub 2010 Jun 10.
Proteases regulate a plethora of biological processes. Because they irreversibly cleave peptide bonds, the activity of proteases is strictly controlled. While there are many ways to regulate protease activity, an emergent mechanism is the modulation of protease function by small molecules acting at allosteric sites. This mode of regulation holds the potential to allow for the specific and temporal control of a given biological process using small molecules. These compounds also serve as useful tools for studying protein dynamics and function. This review highlights recent advances in identifying and characterizing natural and synthetic small molecule allosteric regulators of proteases and discusses their utility in studies of protease function, drug discovery and protein engineering.
蛋白酶调节众多生物过程。由于它们能不可逆地切割肽键，蛋白酶的活性受到严格控制。虽然有多种调节蛋白酶活性的方式，但一种新出现的机制是小分子通过作用于别构位点来调节蛋白酶功能。这种调节模式有可能利用小分子对特定生物过程进行特异性和时效性控制。这些化合物也是研究蛋白质动力学和功能的有用工具。本综述重点介绍了在鉴定和表征蛋白酶的天然和合成小分子别构调节剂方面的最新进展，并讨论了它们在蛋白酶功能研究、药物发现和蛋白质工程中的应用。
