Evidence for the formation of a Mo-H intermediate in the catalytic cycle of formate dehydrogenase.
DFT/BP86/TZVP and DFT/B3LYP/TZVP have been used to investigate systematically the reaction pathways associated with the H-transfer step, which is the rate-determining step of the reaction HCOO(-) ⇄ CO(2) + H(+) + 2e(-), as catalyzed by metalloenzyme formate dehydrogenase (FDH). Actually, the energetics associated with the transfer from formate to all H (proton or hydride) acceptors that are present within the FDH active site have been sampled. This study points to a viable intimate mechanism in which the metal center mediates H transfer from formate to the final acceptor, i.e. a selenocysteine residue. The Mo-based reaction pathway, consisting of a β-H elimination to metal with concerted decarboxylation, turned out to be favored over previously proposed routes in which proton transfer occurs directly from HCOO(-) to selenocysteine. The proposed reaction pathway is reminiscent of the key step of metal-based catalysis of the water-gas shift reaction.
Department of Biotechnology and Biosciences, University of Milano-Bicocca, Piazza della Scienza 2, 20126 Milan, Italy.
Matteo
M
Tiberti
Elena
E
Papaleo
Nino
N
Russo
Luca
L
De Gioia
Giuseppe
G
Zampella
D001426:Bacterial Proteins / Q000737:chemistry*; D001665:Binding Sites; D055162:Biocatalysis; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000737:chemistry / Q000201:enzymology; D005560:Formate Dehydrogenases / Q000737:chemistry*; D005561:Formates / Q000737:chemistry*; D007700:Kinetics; D008667:Metalloproteins / Q000737:chemistry*; D008958:Models, Molecular; D008982:Molybdenum / Q000737:chemistry*; D011522:Protons; D011789:Quantum Theory; D017279:Selenocysteine / Q000737:chemistry*; D055672:Static Electricity; D013816:Thermodynamics
D001426:Bacterial Proteins; D005561:Formates; D008667:Metalloproteins; D011522:Protons; D017279:Selenocysteine; C030544:formic acid; D008982:Molybdenum; D005560:Formate Dehydrogenases