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

DOI

10.1021/ja072650+

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.

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