丝氨酸蛋白酶对酰胺的裂解是通过涉及四面体中间体的逐步途径发生的吗？
Do cleavages of amides by serine proteases occur through a stepwise pathway involving tetrahedral intermediates?
作者信息
Komiyama M, Bender M L
出版信息
Proc Natl Acad Sci U S A. 1979 Feb;76(2):557-60. doi: 10.1073/pnas.76.2.557.
Abstract
The mechanism of the serine protease-catalyzed cleavage of amides (acylation) was examined in terms of the basicity of the functional groups participating in the catalysis. It is proposed that the reaction does not proceed through a stepwise pathway, as opposed to the cleavage of esters and anilides, which start with general base-catalyzed formation of the tetrahedral intermediate followed by its general acid-catalyzed breakdown. Instead, the proton abstracted from the hydroxyl group of the serine by the imidazolyl group of the histidine is donated to the nitrogen atom of the leaving group of the amide before the bond between the carbonyl carbon atom of the amide and the attacking serine oxygen atom is completed. Reactions proceed by a SN2-like reaction through the cooperation of acid catalysis by the imidazolyl cation and nucleophilic attack by the serine. The mechanisms of the enzymatic hydrolyses of anilides and esters proceed through a discrete tetrahedral intermediate, but the enzymatic hydrolyses of amides probably do not.
摘要
从参与催化的官能团的碱性角度，对丝氨酸蛋白酶催化酰胺裂解（酰化）的机制进行了研究。与酯和酰苯胺的裂解不同，酯和酰苯胺的裂解起始于一般碱催化的四面体中间体的形成，随后是其一般酸催化的分解，而有人提出该反应并非通过逐步途径进行。相反，在酰胺的羰基碳原子与进攻的丝氨酸氧原子之间的键形成之前，组氨酸的咪唑基从丝氨酸的羟基夺取的质子被给予酰胺离去基团的氮原子。反应通过类似SN2的反应进行，通过咪唑阳离子的酸催化与丝氨酸的亲核进攻协同作用。酰苯胺和酯的酶促水解机制通过离散的四面体中间体进行，但酰胺的酶促水解可能并非如此。
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