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A QM/MM investigation of the activation and catalytic mechanism of Fe-only hydrogenases

Greco, Claudio LU ; Bruschi, Maurizio; De Gioia, Luca and Ryde, Ulf LU (2007) In Inorganic Chemistry 46(15). p.5911-5921
Abstract
Fe-only hydrogenases are enzymes that catalyze dihydrogen production or oxidation, due to the presence of an unusual Fe6S6 cluster (the so-called H-cluster) in their active site, which is composed of a Fe2S2 subsite, directly involved in catalysis, and a classical Fe4S4 cubane cluster. Here, we present a hybrid quantum mechanical and molecular mechanical (QM/MM) investigation of the Fe-only hydrogenase from Desulfovibrio desulfuricans, in order to unravel key issues regarding the activation of the enzyme from its completely oxidized inactive state (H-ox(inac)) and the influence of the protein environment on the structural and catalytic properties of the H-cluster. Our results show that the Fe2S2 subcluster in the (FeFeII)-Fe-II redox... (More)
Fe-only hydrogenases are enzymes that catalyze dihydrogen production or oxidation, due to the presence of an unusual Fe6S6 cluster (the so-called H-cluster) in their active site, which is composed of a Fe2S2 subsite, directly involved in catalysis, and a classical Fe4S4 cubane cluster. Here, we present a hybrid quantum mechanical and molecular mechanical (QM/MM) investigation of the Fe-only hydrogenase from Desulfovibrio desulfuricans, in order to unravel key issues regarding the activation of the enzyme from its completely oxidized inactive state (H-ox(inac)) and the influence of the protein environment on the structural and catalytic properties of the H-cluster. Our results show that the Fe2S2 subcluster in the (FeFeII)-Fe-II redox statewhich is experimentally observed for the completely oxidized form of the enzymebinds a water molecule to one of its metal centers. The computed QM/MM energy values for water binding to the diferrous subsite are in fact over 70 kJ mol(-1); however, the affinity toward water decreases by 1 order of magnitude after a one-electron reduction of H-ox(inact), thus leading to the release of coordinated water from the H-cluster. The investigation of a catalytic cycle of the Fe-only hydrogenase that implies formation of a terminal hydride ion and a di(thiomethyl)amine (DTMA) molecule acting as an acid/base catalyst indicates that all steps have reasonable reaction energies and that the influence of the protein on the thermodynamic profile of H-2 production catalysis is not negligible. QM/MM results show that the interactions between the Fe2S2 subsite and the protein environment could give place to structural rearrangements of the H-cluster functional for catalysis, provided that the bidentate ligand that bridges the iron atoms in the binuclear subsite is actually a DTMA residue. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Inorganic Chemistry
volume
46
issue
15
pages
5911 - 5921
publisher
The American Chemical Society
external identifiers
  • wos:000248011300019
  • scopus:34547651339
ISSN
1520-510X
DOI
10.1021/ic062320a
language
English
LU publication?
yes
id
060cf4d6-39a1-4ca6-b295-497870692040 (old id 645743)
date added to LUP
2007-12-07 12:56:47
date last changed
2017-10-01 03:51:53
@article{060cf4d6-39a1-4ca6-b295-497870692040,
  abstract     = {Fe-only hydrogenases are enzymes that catalyze dihydrogen production or oxidation, due to the presence of an unusual Fe6S6 cluster (the so-called H-cluster) in their active site, which is composed of a Fe2S2 subsite, directly involved in catalysis, and a classical Fe4S4 cubane cluster. Here, we present a hybrid quantum mechanical and molecular mechanical (QM/MM) investigation of the Fe-only hydrogenase from Desulfovibrio desulfuricans, in order to unravel key issues regarding the activation of the enzyme from its completely oxidized inactive state (H-ox(inac)) and the influence of the protein environment on the structural and catalytic properties of the H-cluster. Our results show that the Fe2S2 subcluster in the (FeFeII)-Fe-II redox statewhich is experimentally observed for the completely oxidized form of the enzymebinds a water molecule to one of its metal centers. The computed QM/MM energy values for water binding to the diferrous subsite are in fact over 70 kJ mol(-1); however, the affinity toward water decreases by 1 order of magnitude after a one-electron reduction of H-ox(inact), thus leading to the release of coordinated water from the H-cluster. The investigation of a catalytic cycle of the Fe-only hydrogenase that implies formation of a terminal hydride ion and a di(thiomethyl)amine (DTMA) molecule acting as an acid/base catalyst indicates that all steps have reasonable reaction energies and that the influence of the protein on the thermodynamic profile of H-2 production catalysis is not negligible. QM/MM results show that the interactions between the Fe2S2 subsite and the protein environment could give place to structural rearrangements of the H-cluster functional for catalysis, provided that the bidentate ligand that bridges the iron atoms in the binuclear subsite is actually a DTMA residue.},
  author       = {Greco, Claudio and Bruschi, Maurizio and De Gioia, Luca and Ryde, Ulf},
  issn         = {1520-510X},
  language     = {eng},
  number       = {15},
  pages        = {5911--5921},
  publisher    = {The American Chemical Society},
  series       = {Inorganic Chemistry},
  title        = {A QM/MM investigation of the activation and catalytic mechanism of Fe-only hydrogenases},
  url          = {http://dx.doi.org/10.1021/ic062320a},
  volume       = {46},
  year         = {2007},
}