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Communication
Mechanistic Insights into Cyclooxygenase Irreversible Inactivation by Aspirin
Article first published online: 19 MAR 2009
DOI: 10.1002/cmdc.200800438
Copyright © 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Additional Information
How to Cite
Tosco, P. and Lazzarato, L. (2009), Mechanistic Insights into Cyclooxygenase Irreversible Inactivation by Aspirin. ChemMedChem, 4: 939–945. doi: 10.1002/cmdc.200800438
Publication History
- Issue published online: 28 MAY 2009
- Article first published online: 19 MAR 2009
- Manuscript Revised: 12 FEB 2009
- Manuscript Received: 15 DEC 2008
Funded by
- Italian Ministry for Education, University and Research
Keywords:
- aspirin;
- acylation;
- cyclooxygenases;
- enzyme catalysis;
- quantum chemistry
Abstract
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.