Abstract
Formate dehydrogenases (FDHs) are metalloenzymes that catalyse the reversible conversion of formate to carbon dioxide. Since such a process may be used to combat the greenhouse effect, FDHs have been extensively studied by experimental and theoretical methods. However, the reaction mechanism is still not clear; instead five putative mechanisms have been suggested. In this work, the reaction mechanism of FDH was studied by computational methods. Combined quantum mechanical and molecular mechanic (QM/MM) optimisations were performed to obtain the geometries. To get more accurate energies and obtain a detailed account of the surroundings, big-QM calculations with a very large (1121 atoms) QM region were performed. Our results indicate that the formate substrate does not coordinate directly to Mo when it enters the oxidised active site of the FDH, but instead resides in the second coordination sphere. The sulfido ligand abstracts a hydride ion from the substrate, giving a Mo(IV)–SH state and a thiocarbonate ion attached to Cys196. The latter releases CO2 when the active site is oxidised back to the resting (MoVI) state. This mechanism is supported by recent experimental studies.
Highlights
Biological transformations of carbon dioxide (CO2) are key processes in the global carbon cycle and have lately attracted great attention, because they may be used to combat the greenhouse effect [1,2,3,4,5,6,7]
We have studied the reaction mechanism of formate dehydrogenases (FDHs)
Geometries were obtained by quantum mechanical and molecular mechanic (QM/MM) optimisations at the TPSS/def2-SV(P) level of theory with the surrounding protein outside the QM system fixed at the crystal structure
Summary
Biological transformations of carbon dioxide (CO2) are key processes in the global carbon cycle and have lately attracted great attention, because they may be used to combat the greenhouse effect [1,2,3,4,5,6,7]. The FDHs are divided into two classes, based on whether they require metal ions for their activity or not: metal independent [12,13,14,15,16,17] and metal dependent [8, 18] The former class comprises NAD-dependent enzymes that belong to the D-specific dehydrogenases of the 2-oxyacid family and can be widely found in bacteria, yeasts, fungi and plants. The latter class comprises prokaryotic enzymes that harbour one tungsten (W) or molybdenum (Mo) ion in their active sites [4, 8,9,10]. We will focus on the Mo-FDHs in this paper
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
