title: Quantum chemical modeling of CO oxidation by the active site of molybdenum CO dehydrogenase.
abstract: The catalytic mechanism of molybdenum containing CO dehydrogenase has been studied using hybrid DFT methods with quite large chemical models. The recent high-resolution X-ray structure, showing the surprising presence of copper linked to molybdenum, was used as a starting point. A pathway was initially found with a low barrier for C-O bond formation and CO2 release. However, this pathway did not include the formation of any S-CO2 species, which had been suggested by experiments with an n-butylisocyanide inhibitor. When these SCO2 structures were studied they were found to lead to deep minima, making CO2 release much more difficult. A large effort was spent, including investigations of other spin states, varying the number of protons and electrons, adding water, etc., until a plausible pathway for S-C bond cleavage was found. In this pathway a water molecule is inserted in between molybdenum and the SCO2 group. Full catalytic cycles, including electron and proton transfers, are constructed both with and without S-C bond formation. When these pathways are extended to two full catalytic cycles it can be understood why the formation of the S-C bond actually makes catalysis faster, even though the individual step of CO2 release becomes much more difficult. These results agree well with experimental findings.
authors.affiliation: Department of Physics, Stockholm Centre for Physics, Astronomy and Biotechnology (SC-FAB), Stockholm University, S-106 91 Stockholm, Sweden. ps@physto.se
authors.forename: Per E M
authors.initials: PE
authors.lastname: Siegbahn
authors.forename: Alexander F
authors.initials: AF
authors.lastname: Shestakov
mesh_terms: D000445:Aldehyde Oxidoreductases / Q000737:chemistry* / Q000378:metabolism; D002245:Carbon Dioxide / Q000378:metabolism; D002248:Carbon Monoxide / Q000378:metabolism; D002384:Catalysis; D003300:Copper / Q000737:chemistry; D018360:Crystallography, X-Ray; D008667:Metalloproteins / Q000737:chemistry* / Q000378:metabolism; D008956:Models, Chemical; D008968:Molecular Conformation; D015394:Molecular Structure; D008982:Molybdenum / Q000737:chemistry*; D009097:Multienzyme Complexes / Q000737:chemistry* / Q000378:metabolism; D010084:Oxidation-Reduction
chemical_list: D008667:Metalloproteins; D009097:Multienzyme Complexes; D002245:Carbon Dioxide; D003300:Copper; D002248:Carbon Monoxide; D008982:Molybdenum; D000445:Aldehyde Oxidoreductases; C019823:carbon monoxide dehydrogenase