title: A density functional theory investigation on the mechanism of the second half-reaction of nitric oxide synthase.
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 -O(in)H- proton is transferred back onto the substrate's -NO oxygen then subsequently onto the outer oxygen of the resulting Fe(heme)-OOH species. As a result, O(out) is released as H2O with concomitant formation of a compound I-type (Fe(heme)-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 Fe(heme)-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 N(omega)-hydroxy-L-arginine is also discussed.
authors.affiliation: Department of Chemistry and Biochemistry, University of Windsor, Windsor, Ontario N9B 3P4, Canada.
authors.forename: Jesse J
authors.initials: JJ
authors.lastname: Robinet
authors.forename: Kyung-Bin
authors.initials: KB
authors.lastname: Cho
authors.forename: James W
authors.initials: JW
authors.lastname: Gauld
mesh_terms: D001120:Arginine / Q000031:analogs & derivatives / Q000737:chemistry; D001665:Binding Sites; D002956:Citrulline / Q000138:chemical synthesis / Q000737:chemistry; D003198:Computer Simulation; D006418:Heme / Q000737:chemistry; D008956:Models, Chemical; D015394:Molecular Structure; D009569:Nitric Oxide / Q000138:chemical synthesis / Q000737:chemistry; D019001:Nitric Oxide Synthase / Q000737:chemistry*; D010084:Oxidation-Reduction; D010100:Oxygen / Q000737:chemistry; D011789:Quantum Theory
chemical_list: D002956:Citrulline; D009569:Nitric Oxide; D006418:Heme; D001120:Arginine; D019001:Nitric Oxide Synthase; D010100:Oxygen