Engh R A, Huber R, Bode W, Schulze A J
Abteilung Struketurforschung, Max-Planck-Institut für Biochemie, Martinsried, Germany.
Trends Biotechnol. 1995 Dec;13(12):503-10. doi: 10.1016/S0167-7799(00)89013-7.
The most important of diverse serpin functions is serine-protease inhibition. In contrast to the 'standard-mechanism' inhibitors, inhibitory serpins use a mechanism that involves unusual flexibility, and cofactor and receptor interactions. The principal feature is a refolding step, during which a disordered or helical strand is inserted into the center of a beta sheet. This transition, which is essential for inhibition, can be induced by heating, proteolytic cleavage of the serpin, or complexation with the proteinase target; analogous transitions can be induced by peptide complexation or aggregation. Although it is difficult to determine the details of this mechanism, information derived from crystal structures and other experiments has stimulated drug design efforts with wide-ranging potential applications.
丝氨酸蛋白酶抑制剂（serpin）多种功能中最重要的是丝氨酸蛋白酶抑制作用。与“标准机制”抑制剂不同，抑制性丝氨酸蛋白酶抑制剂采用的机制涉及异常的灵活性以及辅因子和受体相互作用。其主要特征是重折叠步骤，在此过程中，一条无序或螺旋链插入β折叠的中心。这种转变对于抑制作用至关重要，可通过加热、丝氨酸蛋白酶抑制剂的蛋白水解切割或与蛋白酶靶点的复合作用来诱导；类似的转变可由肽复合或聚集诱导。尽管难以确定该机制的细节，但从晶体结构和其他实验中获得的信息推动了具有广泛潜在应用的药物设计工作。
