Structural insights into the active-ready form of [FeFe]-Hydrogenase and mechanistic details of its inhibition by carbon monoxide

Research output: Contribution to journalArticle


[FeFe]-Hydrogenases harbor a {2Fe3S} assembly bearing two CO and two CN- groups, a mu-CO ligand, and a vacant coordination site trans to the mu-CO group. Recent theoretical results obtained studying the isolated {2Fe3S} subsite indicated that one of the CN- ligands can easily move from the crystallographic position to the coordination site trans to the mu-CO group; such an isomerization would have a major impact on substrates and inhibitors binding regiochemistry and, consequently, on the catalytic mechanism. To shed light on this crucial issue, we have carried out hybrid QM/MM and free energy perturbation calculations on the whole enzyme, which demonstrate that the protein environment plays a crucial role and maintains the CN- group fixed in the position observed in the crystal structure; these results strongly support the hypothesis that the vacant coordination site trans to the mu-CO group has a crucial functional relevance both in the context of CO-mediated inhibition of the enzyme and in dihydrogen oxidation/evolution catalysis.


  • Claudio Greco
  • Maurizio Bruschi
  • Jimmy Heimdal
  • Piercarlo Fantucci
  • Luca De Gioia
  • Ulf Ryde
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Theoretical Chemistry
Original languageEnglish
Pages (from-to)7256-7258
JournalInorganic Chemistry
Issue number18
Publication statusPublished - 2007
Publication categoryResearch

Bibliographic note

The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Theoretical Chemistry (S) (011001039)