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Mechanistic and Physiological Implications of the Interplay among Iron-Sulfur Clusters in [FeFe]-Hydrogenases. A QM/MM Perspective

Greco, Claudio; Bruschi, Maurizio; Fantucci, Piercarlo; Ryde, Ulf LU and De Gioia, Luca (2011) In Journal of the American Chemical Society 133(46). p.18742-18749
Abstract
Key stereoelectronic properties of Desulfovibrio desulfuricans [FeFe]-hydrogenase (DdH) were investigated by quantum mechanical description of its complete inorganic core, which includes a Fe6S6 active site (the H-cluster), as well as two ancillary Fe4S4 assemblies (the F and F' clusters). The partially oxidized, active-ready form of DdH is able to efficiently bind dihydrogen, thus starting H-2 oxidation catalysis. The calculations allow us to unambiguously assign a mixed Fe(H)Fe(I) state to the catalytic core of the active-ready enzyme and show that H-2 uptake exerts subtle, yet crucial influences on the redox properties of DdH. In fact, H-2 binding can promote electron transfer from the H-cluster to the solvent-exposed F'-cluster, thanks... (More)
Key stereoelectronic properties of Desulfovibrio desulfuricans [FeFe]-hydrogenase (DdH) were investigated by quantum mechanical description of its complete inorganic core, which includes a Fe6S6 active site (the H-cluster), as well as two ancillary Fe4S4 assemblies (the F and F' clusters). The partially oxidized, active-ready form of DdH is able to efficiently bind dihydrogen, thus starting H-2 oxidation catalysis. The calculations allow us to unambiguously assign a mixed Fe(H)Fe(I) state to the catalytic core of the active-ready enzyme and show that H-2 uptake exerts subtle, yet crucial influences on the redox properties of DdH. In fact, H-2 binding can promote electron transfer from the H-cluster to the solvent-exposed F'-cluster, thanks to a 50% decrease of the energy gap between the HOMO (that is localized on the H-cluster) and the LUMO (which is centered on the F'-cluster). Our results also indicate that the binding of the redox partners of DdH in proximity of its F'-cluster can trigger one-electron oxidation of the H-2-bound enzyme, a process that is expected to have an important role in H-2 activation. Our findings are analyzed not only from a mechanistic perspective, but also in consideration of the physiological role of DdH. In fact, this enzyme is known to be able to catalyze both the oxidation and the evolution of H-2, depending on the cellular metabolic requirements. Hints for the design of targeted mutations that could lead to the enhancement of the oxidizing properties of DdH are proposed and discussed. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of the American Chemical Society
volume
133
issue
46
pages
18742 - 18749
publisher
The American Chemical Society
external identifiers
  • wos:000297398900045
  • scopus:83055179384
ISSN
1520-5126
DOI
10.1021/ja205542k
language
English
LU publication?
yes
id
d0b99a11-d1ea-4253-ade7-97cc3e13a101 (old id 2272006)
date added to LUP
2011-12-29 14:26:04
date last changed
2017-11-05 04:15:15
@article{d0b99a11-d1ea-4253-ade7-97cc3e13a101,
  abstract     = {Key stereoelectronic properties of Desulfovibrio desulfuricans [FeFe]-hydrogenase (DdH) were investigated by quantum mechanical description of its complete inorganic core, which includes a Fe6S6 active site (the H-cluster), as well as two ancillary Fe4S4 assemblies (the F and F' clusters). The partially oxidized, active-ready form of DdH is able to efficiently bind dihydrogen, thus starting H-2 oxidation catalysis. The calculations allow us to unambiguously assign a mixed Fe(H)Fe(I) state to the catalytic core of the active-ready enzyme and show that H-2 uptake exerts subtle, yet crucial influences on the redox properties of DdH. In fact, H-2 binding can promote electron transfer from the H-cluster to the solvent-exposed F'-cluster, thanks to a 50% decrease of the energy gap between the HOMO (that is localized on the H-cluster) and the LUMO (which is centered on the F'-cluster). Our results also indicate that the binding of the redox partners of DdH in proximity of its F'-cluster can trigger one-electron oxidation of the H-2-bound enzyme, a process that is expected to have an important role in H-2 activation. Our findings are analyzed not only from a mechanistic perspective, but also in consideration of the physiological role of DdH. In fact, this enzyme is known to be able to catalyze both the oxidation and the evolution of H-2, depending on the cellular metabolic requirements. Hints for the design of targeted mutations that could lead to the enhancement of the oxidizing properties of DdH are proposed and discussed.},
  author       = {Greco, Claudio and Bruschi, Maurizio and Fantucci, Piercarlo and Ryde, Ulf and De Gioia, Luca},
  issn         = {1520-5126},
  language     = {eng},
  number       = {46},
  pages        = {18742--18749},
  publisher    = {The American Chemical Society},
  series       = {Journal of the American Chemical Society},
  title        = {Mechanistic and Physiological Implications of the Interplay among Iron-Sulfur Clusters in [FeFe]-Hydrogenases. A QM/MM Perspective},
  url          = {http://dx.doi.org/10.1021/ja205542k},
  volume       = {133},
  year         = {2011},
}