Computational Characterization of Reactive Intermediates of Carbon Monoxide Dehydrogenase

The catalytic oxidation of CO to CO_2 by carbon monoxide dehydrogenases has been explored theoretically, and a large C-cluster model including the metal core Ni-4Fe-4S] and surrounding residues and crystal water molecules was used in density functional calculations. The key species involved in the oxidation of CO at the C-cluster, C_(red1), C_(red2) and C_(int), have been elucidated. On the basis of computational results, the plausible enzymatic mechanism for the CO oxidation was proposed. In the catalytic reaction, the first proton abstraction from the Fe(1)-bound water leads to a precursor to accommodate CO binding and the subsequently consecutive proton transfers from the metal-bound carboxylate to the amino acid residues facilitate the release of CO_2. The hydrogen-bond network around the C-cluster formed by conserved residues His93, His96, Glu299, Lys563, and four water molecules in the active domain plays an important role in proton transfer and intermediate stabilization. Predicted geometries of key species show good agreement with the reported crystal structures.