Reaction mechanism of formate dehydrogenase studied by computational methods

Research output: Contribution to journalArticle


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.


External organisations
  • Shantou University
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Biochemistry and Molecular Biology


  • Density functional theory, Formate dehydrogenase, Molybdenum, QM/MM, Sulfur-shift mechanism
Original languageEnglish
Pages (from-to)1243-1254
JournalJournal of Biological Inorganic Chemistry
Issue number8
Early online date2018 Sep 1
Publication statusPublished - 2018 Dec
Publication categoryResearch