Structural Insights into the Active-Ready Form of [FeFe]-Hydrogenase
and Mechanistic Details of Its Inhibition by Carbon Monoxide
Claudio Greco
Maurizio Bruschi
Jimmy Heimdal
Piercarlo Fantucci
Luca De Gioia
Ulf Ryde
10.1021/ic701051h.s002
https://acs.figshare.com/articles/journal_contribution/Structural_Insights_into_the_Active_Ready_Form_of_FeFe_Hydrogenase_and_Mechanistic_Details_of_Its_Inhibition_by_Carbon_Monoxide/2987989
[FeFe]-Hydrogenases harbor a {2Fe3S} assembly bearing two
CO and two CN<sup>-</sup> groups, a μ-CO ligand, and a vacant coordination
site trans to the μ-CO group. Recent theoretical results obtained
studying the <i>isolated</i> {2Fe3S} subsite indicated that one of the
CN<sup>-</sup> ligands can easily move from the crystallographic position to
the coordination site trans to the μ-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<sup>-</sup> group fixed in the position
observed in the crystal structure; these results strongly support
the hypothesis that the vacant coordination site trans to the μ-CO
group has a crucial functional relevance both in the context of
CO-mediated inhibition of the enzyme and in dihydrogen oxidation/evolution catalysis.
2007-09-03 00:00:00
crystal structure
3S
inhibitors binding regiochemistry
energy perturbation calculations
CO
ligand
QM
enzyme
Fe
coordination site trans
CN
Structural Insights
Mechanistic Details
protein environment