Formate dehydrogenase

Formate dehydrogenases are a set of enzymes that catalyse the oxidation of formate to carbon dioxide, donating the electrons to a second substrate, such as NAD+ in formate:NAD+ oxidoreductase () or to a cytochrome in formate:ferricytochrome-b1 oxidoreductase (). This family of enzymes has attracted attention as inspiration or guidance on methods for the carbon dioxide fixation, relevant to global warming. NAD-dependent formate dehydrogenases are important in methylotrophic yeast and bacteria, being vital in the catabolism of C1 compounds such as methanol. The cytochrome-dependent enzymes are more important in anaerobic metabolism in prokaryotes. For example, in E. coli, the formate:ferricytochrome-b1 oxidoreductase is an intrinsic membrane protein with two subunits and is involved in anaerobic nitrate respiration. NAD-dependent reaction Formate + NAD+ CO2 + NADH + H+ Cytochrome-dependent reaction Formate + 2 ferricytochrome b1 CO2 + 2 ferrocytochrome b1 + 2 H+ The metal-dependent Fdh's feature Mo or W at their active sites. These active sites resemble the motif seen in DMSO reductase, with two molybdopterin cofactors bound to Mo/W in a bidentate fashion. The fifth and sixth ligands are sulfide and either cysteinate or selenocysteinate. The mechanism of action appears to involve 2e redox of the metal centers, induced by hydride transfer from formate and release of carbon dioxide: In this scheme, represents the four thiolate-like ligands provided by the two dithiolene cofactors, the molybdopterins. The dithiolene and cysteinyl/selenocysteinyl ligands are redox-innocent. In terms of the molecular details, the mechanism remains uncertain, despite numerous investigations. Most mechanisms assume that formate does not coordinate to Mo/W, in contrast to typical Mo/W oxo-transferases (e.g., [[dmso reductase). A popular mechanistic proposal entails transfer of H- from formate to the Mo/WVI=S group. Formate dehydrogenase consists of two transmembrane domains; three α-helices of the β-subunit and four transmembrane helices from the gamma-subunit.