Molybdenum-containing carbon monoxide dehydrogenase (Mo-CODH) from the aerobic bacterium Oligotropha carboxidovarans is an iron-sulfur flavoprotein that catalyzes the conversion of CO to CO2 at a dimetallic Mo-Cu active site, yielding protons and electrons. The catalytically active state has been structurally characterized to be the Mo(VI)-Cu(I) state; however, the coordination environment around the metal centers remain uncetain.1 Previous computational studies are too preliminary to achieve a reasonable agreement with the experimental findings, as the effects of the protein environment are often neglected.2 A systematic model building approach for the Mo(VI)-Cu(I) state has been employed to understand the effects of the protein environment on several CODH models using QM methods. Our extended model (199 atoms) revealed important second sphere interactions that are essential for an open active site where Mo and Cu remain at a reasonable distance (~ 3.7 �) (Figure 1). Without the appropriate protein environment, most models resulted in a closed system where Mo-Cu distances are significantly shorter (~ 2.6 to 3.0 �) than the crystallographic Mo-Cu distance of 3.7 �, and the metal centers are often linked by bridging hydroxo ligand (Figure 1 inset). These extended models are being validated using spectroscopic data. As these QM models are too large to investigate the catalytic mechanism with better accuracy and computational efficiency, we have been developing QM-MM models to study the different redox states, and the overall catalytic mechanism of Mo-CODH.References: 1. Dobbek, H.; Gremer, L.; Kiefersauer, R., Huber, R.; Meyer, O. PNAS 2002  , 99 (25), 15971-15976. 2. Siegbahn, P.E.M.; Shestakov, A. F. J. Comp. Chem., 2005  , 25 (9), 888-898.

Study of molybdenum-containing carbon monoxide dehydrogenase using QM-MM methods

248th National Meeting (2014)

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