Mechanistic Insights into Cyclooxygenase Irreversible Inactivation by Aspirin

被引：32

作者：

Tosco, Paolo ^{[1
]}

Lazzarato, Loretta ^{[1
]}

机构：

[1] Univ Turin, Dipartimento Sci & Tecnol Farmaco, I-10125 Turin, Italy

来源：

CHEMMEDCHEM | 2009年 / 4卷 / 06期

关键词：

aspirin; acylation; cyclooxygenases; enzyme catalysis; quantum chemistry; AUTOMATED DOCKING; CRYSTAL-STRUCTURE; BETA-LACTAMASE; ACETYLATION; CATALYSIS; INHIBITION; HYDROLYSIS; PROTEINS; KINETICS; ENERGY;

D O I：

10.1002/cmdc.200800438

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

(Figure Presented) A mechanistic hypothesis for the acetylation of cyclooxygenase (COX) by aspirin is proposed on the basis of a QM/MM study. This mechanism is consistent with previous experimental findings by other investigators. Ser 530 appears to be acetylated under intramolecular general base catalysis provided by the carboxylate moiety of aspirin, while Tyr 385 plays a crucial role in orienting and polarizing the acetyl group. © 2009 Wiley-VCH Verlag GmbH & Co. KGaA.

引用

页码：939 / 945

页数：7

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