Toward a Chemical Mechanism of Proton Pumping by the B-Type Cytochrome c Oxidases: Application of Density Functional Theory to Cytochrome ba[sub3] of Thermus thermophilus.

A mechanism for proton pumping by the B-type cytochrome c oxidases is presented in which one proton is pumped in conjunction with the weakly exergonic, two-electron reduction of Fe-bound O[sub2] to the Fe-Cu bridging peroxodianion and three protons are pumped in conjunction with the highly exergonic...

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Publicado en:Journal of the American Chemical Society Vol. 130; no. 45; pp. 15002 - 15022
Autores principales: Fee, James A., Case, David A., Noodleman, Louis
Formato: Artículo
Publicado: American Chemical Society 11/12/2008
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Acceso en línea:Ver este registro en EBSCOhost
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      dt: 11/12/2008
      vid: 130
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      pub: American Chemical Society
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        35398449
        10.1021/ja803112w
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        atl: Toward a Chemical Mechanism of Proton Pumping by the B-Type Cytochrome c Oxidases: Application of Density Functional Theory to Cytochrome ba[sub3] of Thermus thermophilus.
      aug:
        au:
          Fee, James A.
          Case, David A.
          Noodleman, Louis
        affil: Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037
      su:
        Protons
        Cytochrome c
        Oxidases
        Density functionals
        Enzyme activation
        Chemical reduction
        Imidazoles
        Electrons
        Bilayer lipid membranes
      sug:
        subj:
          Protons
          Cytochrome c
          Oxidases
          Density functionals
          Enzyme activation
          Chemical reduction
          Imidazoles
          Electrons
          Bilayer lipid membranes
      ab: A mechanism for proton pumping by the B-type cytochrome c oxidases is presented in which one proton is pumped in conjunction with the weakly exergonic, two-electron reduction of Fe-bound O[sub2] to the Fe-Cu bridging peroxodianion and three protons are pumped in conjunction with the highly exergonic, two-electron reduction of Fe(lll)-[sup-]O-O[sup-]-Cu(ll) to form water and the active oxidized enzyme, Fe(lll)-[sup-]OH,Cu(ll). The scheme is based on the active-site structure of cytochrome ba[sub3] from Thermus the rmophllus, which is considered to be both necessary and sufficient for coupled O[sub2] reduction and proton pumping when appropriate gates are in place (not included in the model). Fourteen detailed structures obtained from density functional theory (DFT) geometry optimization are presented that are reasonably thought to occur during the four-electron reduction of O[sub2]. Each proton-pumping step takes place when a proton resides on the imidazole ring of l-His376 and the large active-site cluster has a net charge of +1 due to an uncompensated, positive charge formally associated with Cu[subB]. Four types of DFT were applied to determine the energy of each intermediate, and standard thermochemical approaches were used to obtain the reaction free energies for each step in the catalytic cycle. This application of DFT generally conforms with previously suggested criteria for a valid model (Siegbahn, P. E. M.; Blomberg, M. A. R. Chem. Rev. 2000, 100, 421-437) and shows how the chemistry of O[sub2] reduction in the heme a[sub3]-Cu[subB] dinuclear center can be harnessed to generate an electrochemical proton gradient across the lipid bilayer.
      pubtype: Academic Journal
      doctype: Article
      src: R
    language: English
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          year: 2008
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