A Density Functional Theory Investigation on the Mechanism of the Second Half-Reaction of Nitric Oxide Synthase

Authors

Jesse J. Robinet, University of Windsor
Kyung-Bin Cho, University of Windsor
James Gauld, University of WindsorFollow

Author ORCID Identifier

https://orcid.org/0000-0002-2956-9781

Document Type

Article

Publication Date

2-2008

Publication Title

Journal of the American Chemical Society

Volume

130

Issue

11

First Page

3328

Last Page

3334

Abstract

Density functional theory methods have been employed to systematically investigate the overall mechanism of the second half-reaction of nitric oxide synthases. The initial heme-bound hydrogen peroxide intermediate previously identified is found to first undergo a simple rotation about its O−O peroxide bond. Then, via a “ping-pong” peroxidase-like mechanism the −OinH− proton is transferred back onto the substrate's −NO oxygen then subsequently onto the outer oxygen of the resulting Feheme−OOH species. As a result, Oout is released as H2O with concomitant formation of a compound I-type (Feheme−O) species. Formation of the final citrulline and NO products can then be achieved in one step via a tetrahedral transition structure resulting from direct attack of the Feheme−O moiety at the substrate's guanidinium carbon center. The possible role of alternative mechanisms involving a protonated compound II-type species or an initial transfer of only the −NH− hydrogen of the NHOH+ group of Nω-hydroxy-l-arginine is also discussed.

DOI

10.1021/ja072650+

Recommended Citation

Robinet, Jesse J.; Cho, Kyung-Bin; and Gauld, James. (2008). A Density Functional Theory Investigation on the Mechanism of the Second Half-Reaction of Nitric Oxide Synthase. Journal of the American Chemical Society, 130 (11), 3328-3334.
https://scholar.uwindsor.ca/chemistrybiochemistrypub/128