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Journal of the American Chemical Society
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.
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.
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