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

Summary, in English

[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.

• Författare: Claudio Greco; Maurizio Bruschi; Jimmy Heimdal; Piercarlo Fantucci; Luca De Gioia; Ulf Ryde
• Avdelning/ar: Beräkningskemi
• Publiceringsår: 2007
• Språk: Engelska
• Sidor: 7256-7258
• Publikation/Tidskrift/Serie: Inorganic Chemistry
• Volym: 46
• Issue: 18
• Länkar: http://dx.doi.org/10.1021/ic701051h
• Dokumenttyp: Artikel i tidskrift
• Förlag: The American Chemical Society (ACS)
• Ämne: Theoretical Chemistry
• Status: Published
• ISBN/ISSN/Övrigt: ISSN: 1520-510X