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

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 peroxi...

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Publicado en:Journal of the American Chemical Society Vol. 130; no. 11; pp. 3328 - 3335
Autores principales: Robinet, Jesse J., Kyung-Bin Cho, Gauld, James W.
Formato: Artículo
Publicado: American Chemical Society 3/19/2008
Materias:
Acceso en línea:Ver este registro en EBSCOhost
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      dt: 3/19/2008
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      pub: American Chemical Society
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        10.1021/ja072650+
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        atl: A Density Functional Theory Investigation on the Mechanism of the Second Half-Reaction of Nitric Oxide Synthase.
      aug:
        au:
          Robinet, Jesse J.
          Kyung-Bin Cho
          Gauld, James W.
        affil: Department of Chemistry and Biochemistry, University of Windsor, Windsor, Ontario N9B 3P4, Canada
      su:
        Density functionals
        Nitric oxide
        Hydrogen peroxide
        Nitrogen compounds
        Functional analysis
      sug:
        subj:
          Density functionals
          Nitric oxide
          Hydrogen peroxide
          Nitrogen compounds
          Functional analysis
      ab: 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 OH proton is transferred back onto the substrate's -NO oxygen then subsequently onto the outer oxygen of the resulting FeOOH species. As a result, O is released as HO with concomitant formation of a compound I-type (Fe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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-hydroxy-L-arginine is also discussed.
      pubtype: Academic Journal
      doctype: Article
      src: R
    language: English
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