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

Greco, Claudio LU ; Bruschi, Maurizio; Heimdal, Jimmy LU ; Fantucci, Piercarlo; De Gioia, Luca and Ryde, Ulf LU (2007) In Inorganic Chemistry 46(18). p.7256-7258
Abstract
[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... (More)
[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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Inorganic Chemistry
volume
46
issue
18
pages
7256 - 7258
publisher
The American Chemical Society
external identifiers
  • wos:000248984500011
  • scopus:34548635010
ISSN
1520-510X
DOI
10.1021/ic701051h
language
English
LU publication?
yes
id
8c4d4af8-d7bb-4f24-9b84-c05586d94a5e (old id 688036)
date added to LUP
2007-12-07 12:58:20
date last changed
2017-11-12 03:24:04
@article{8c4d4af8-d7bb-4f24-9b84-c05586d94a5e,
  abstract     = {[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.},
  author       = {Greco, Claudio and Bruschi, Maurizio and Heimdal, Jimmy and Fantucci, Piercarlo and De Gioia, Luca and Ryde, Ulf},
  issn         = {1520-510X},
  language     = {eng},
  number       = {18},
  pages        = {7256--7258},
  publisher    = {The American Chemical Society},
  series       = {Inorganic Chemistry},
  title        = {Structural insights into the active-ready form of [FeFe]-Hydrogenase and mechanistic details of its inhibition by carbon monoxide},
  url          = {http://dx.doi.org/10.1021/ic701051h},
  volume       = {46},
  year         = {2007},
}