Mo-Cu containing carbon monoxide dehydrogenase (CODH) from the aerobic soil bacteria Oligotropha carboxidovorans is an important enzyme in the global carbon cycle, converting toxic carbon monoxide into less toxic carbon dioxide using the reaction: CO + H2O →CO2 + 2H+ + 2e-. The catalytically active state is believed to be the Mo(VI)-Cu(I) state and is reduced to Mo(IV)-Cu(I) during CO oxidation. Despite the close to atomic resolution structure (1.1Å), the active state and the intermediates involved during catalysis are not yet clearly understood and several aspects of the active site remain in question, such as ligand composition around the metal centers, oxidation and spin states of the metals, substrate binding, and possible intermediates formed during the catalytic cycle. To gain further insights, computational models were systematically developed starting from a small inorganic model containing only the first coordination sphere (~ 41 atoms), and extended to a converged model (~ 179 atoms) incorporating important second sphere residues. As expected, smaller models resulted in highly distorted geometries relative to the crystal structure due to the absence of important residues involved in weak interactions around the metal centers. Using our converged model, the role of the important second sphere residues was evaluated using in silico point mutations. Our results revealed that several of these residues are critical to maintain the functionality of a realistic model. These models are currently being evaluated by comparing spectroscopic and redox properties with the available experimental results. To assess the effects of the larger protein environment on the active site, we are implementing integrated quantum mechanics and molecular mechanics (QM/MM) models.

Toxic carbon monoxide removal by the soil bacteria Oligatropha carboxidavorans: Insights from In silico models

249th National Meeting (2015)

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