Issue 5, 2018

Kinetic basis for the activation of human cyclooxygenase-2 rather than cyclooxygenase-1 by nitric oxide

Abstract

Numerous studies have shown that nitric oxide (NO) interacts with human cyclooxygenase (COX); however, conflicting results exist with respect to their interactions. Herein, recombinant human COX-1 and COX-2 were prepared and treated with NO donors individually under anaerobic and aerobic conditions. The S-nitrosylation detection and subsequent kinetic investigations into the arachidonic acid (AA) oxidation of COX enzymes indicate that NO S-nitrosylates both COX-1 and COX-2 in an oxygen-dependent manner, but enhances only the dioxygenase activity of COX-2. The solution viscosity, deuterium kinetic isotope effect (KIE), and oxygen-18 KIE experiments further demonstrate that NO activates COX-2 by altering the protein conformation to stimulate substrate association/product release and by accelerating the rate of hydrogen abstraction from AA by catalytic tyrosine radicals. These novel findings provide useful information for designing new drugs with less cardiotoxic effects that can block the interaction between NO and COX.

Graphical abstract: Kinetic basis for the activation of human cyclooxygenase-2 rather than cyclooxygenase-1 by nitric oxide

Supplementary files

Article information

Article type
Paper
Submitted
04 Dec 2017
Accepted
21 Dec 2017
First published
21 Dec 2017

Org. Biomol. Chem., 2018,16, 765-770

Kinetic basis for the activation of human cyclooxygenase-2 rather than cyclooxygenase-1 by nitric oxide

J. Qiao, L. Ma, J. Roth, Y. Li and Y. Liu, Org. Biomol. Chem., 2018, 16, 765 DOI: 10.1039/C7OB02992F

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements