BINDING OF A POSSIBLE TRANSITION-STATE ANALOG TO THE ACTIVE-SITE OF CARBOXYPEPTIDASE-A
BINDING OF A POSSIBLE TRANSITION-STATE ANALOG TO THE ACTIVE-SITE OF CARBOXYPEPTIDASE-A
复制标题
DOI：
10.1073/pnas.82.20.6840
复制
发表时间：
1985-01-01
影响因子：
11.1
通讯作者：
LIPSCOMB, WN
中科院分区：
文献类型：
--
作者：
CHRISTIANSON, DW;LIPSCOMB, WN
竞争性抑制剂2-苄基-3-甲酰基丙酸与羧肽酶A活性部位的结合方式已用X-射线衍射方法研究到1.7埃的分辨率。与酶结合的实际物质被确定为在醛羰基处共价水合产生的偕二醇。与抑制剂与酶结合过程有关的细节目前尚不清楚：游离醛最初可能与酶结合，随后进行催化水合;或者，水合物本身可能是最初与酶结合的物质，因为它在水溶液中存在的程度很高（25%）。尽管如此，报道的复合物的结构是一个可能的四面体中间体，通过将在一般的碱水解机制中遇到。当然，不能简单地根据这种酶-抑制剂复合物的结构排除其他机制的建议，如酸酐途径。
The mode of binding of the competitive inhibitor 2-benzyl-3-formylpropanoic acid to the active site of carboxypeptidase A has been studied by X-ray diffraction methods to a resolutoin of 1.7 .ANG.. The actual speciesbound to the enzyme was determined to be the gem-diol resulting from covalent hydration at the aldehyde carbonyl. Details relating to the process of association of inhibitor with enzyme are unknown at this time: the free aldehyde could initially bind to the enzyme and subsequently undergo catalytic hydration; or, the hydrate itself could be the species initially binding to the enzyme, because it does exist to a high degree (25%) in aqueous solution. Nevertheless, the structure of the complex reported is reminiscent of a possible tetrahedral intermediate through would be encountered in a general base hydrolytic mechanism. Of course, other mechanistic proposals, such as the anhydride pathway, cannot be ruled out simply on the basis of the structure of this enzyme-inhibitor complex.