The Mechanism of Formate Oxidation by Metal-dependent Formate Dehydrogenases

C. S. MOTA; M. G. RIVAS; C. D. BRONDINO; I. MOURA; J. J. G. MOURA; P. J. GONZÁLEZ; N. M. F. S. A. CERQUEIRA

JOURNAL OF BIOLOGICAL INORGANIC CHEMISTRY

SPRINGER

Año: 2011 vol. 16 p. 1255 - 1268

0949-8257

Metal-dependent formate dehydrogenases (Fdh) from prokaryotic organisms are members of the dimethyl sulfoxide (DMSO) reductase family of mononuclear molybdenum and tungsten containing enzymes. Fdh catalyze the oxidation of the formate anion to carbon dioxide in a redox reaction that involves the transfer of two electrons from the substrate to the active site. The active site in the oxidized state comprises a hexacoordinated Mo or W ion in a trigonal prismatic geometry. Using this structural model, the catalytic mechanism of Fdh has been calculated through DFT tools. The simulated mechanism was correlated with the experimental kinetic properties of three different Fdhs isolated from three different Desulfovibrio species. Our studies indicate that the C-H bond break is the rate-limiting step of the catalytic cycle and that changing Mo for W in the active site does not affect the turnover rates. The role of conserved amino acid residues near the active site is discussed on the basis of theoretical and experimental results.