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:
https://lup.lub.lu.se/record/645743
- author
- Greco, Claudio
LU
; Bruschi, Maurizio
; De Gioia, Luca
and Ryde, Ulf
LU
- organization
- publishing date
- 2007
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Inorganic Chemistry
- volume
- 46
- issue
- 15
- pages
- 5911 - 5921
- publisher
- The American Chemical Society (ACS)
- external identifiers
-
- wos:000248011300019
- scopus:34547651339
- pmid:17602468
- ISSN
- 1520-510X
- DOI
- 10.1021/ic062320a
- language
- English
- LU publication?
- yes
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Theoretical Chemistry (S) (011001039)
- id
- 060cf4d6-39a1-4ca6-b295-497870692040 (old id 645743)
- date added to LUP
- 2016-04-01 12:17:47
- date last changed
- 2025-04-04 14:52:57
@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 (ACS)}},
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}},
doi = {{10.1021/ic062320a}},
volume = {{46}},
year = {{2007}},
}