Wei A, Rubin H, Cooperman B S, Christianson D W
Department of Chemistry, University of Pennsylvania, Philadelphia 19104, USA.
Nat Struct Biol. 1994 Apr;1(4):251-8. doi: 10.1038/nsb0494-251.
The three-dimensional structure of an uncleaved serpin, a variant of human antichymotrypsin engineered to be an inhibitor of human neutrophil elastase, has been determined by X-ray crystallographic methods and is currently being refined at 2.5 A resolution. It contains an intact reactive loop in a distorted helical conformation. A comparison of the current model with that of its cleaved counterpart suggests that the conformational 'stress' of the serpin in its uncleaved and uncomplexed state may not be confined solely to the reactive loop or beta-sheet A. It is intriguing that strand s4A is not pre-inserted into beta-sheet A of the native serpin, and this has profound implications for the mechanism of serpin function.
一种未裂解的丝氨酸蛋白酶抑制剂（serpin）的三维结构已通过X射线晶体学方法确定，该丝氨酸蛋白酶抑制剂是经过工程改造的人抗胰凝乳蛋白酶变体，可作为人中性粒细胞弹性蛋白酶的抑制剂，目前正在以2.5埃的分辨率进行精修。它在扭曲的螺旋构象中包含一个完整的反应环。将当前模型与其裂解后的对应物进行比较表明，处于未裂解和未结合状态的丝氨酸蛋白酶抑制剂的构象“应力”可能不仅局限于反应环或β-折叠A。有趣的是，链s4A并未预先插入天然丝氨酸蛋白酶抑制剂的β-折叠A中，这对丝氨酸蛋白酶抑制剂的功能机制具有深远影响。
