Reaction mechanism of formate dehydrogenase studied by computational methods
Dong, Geng LU and Ryde, Ulf LU
(2018)
In Journal of Biological Inorganic Chemistry
23(8).
p.1243-1254
- Abstract
Formate dehydrogenases (FDHs) are metalloenzymes that catalyse the reversible conversion of formate to carbon dioxide. Since such a process may be used to combat the greenhouse effect, FDHs have been extensively studied by experimental and theoretical methods. However, the reaction mechanism is still not clear; instead five putative mechanisms have been suggested. In this work, the reaction mechanism of FDH was studied by computational methods. Combined quantum mechanical and molecular mechanic (QM/MM) optimisations were performed to obtain the geometries. To get more accurate energies and obtain a detailed account of the surroundings, big-QM calculations with a very large (1121 atoms) QM region were performed. Our results indicate that... (More)
Formate dehydrogenases (FDHs) are metalloenzymes that catalyse the reversible conversion of formate to carbon dioxide. Since such a process may be used to combat the greenhouse effect, FDHs have been extensively studied by experimental and theoretical methods. However, the reaction mechanism is still not clear; instead five putative mechanisms have been suggested. In this work, the reaction mechanism of FDH was studied by computational methods. Combined quantum mechanical and molecular mechanic (QM/MM) optimisations were performed to obtain the geometries. To get more accurate energies and obtain a detailed account of the surroundings, big-QM calculations with a very large (1121 atoms) QM region were performed. Our results indicate that the formate substrate does not coordinate directly to Mo when it enters the oxidised active site of the FDH, but instead resides in the second coordination sphere. The sulfido ligand abstracts a hydride ion from the substrate, giving a Mo(IV)–SH state and a thiocarbonate ion attached to Cys196. The latter releases CO2 when the active site is oxidised back to the resting (MoVI) state. This mechanism is supported by recent experimental studies.
(Less)
- author
- Dong, Geng
LU
and Ryde, Ulf
LU
- organization
- publishing date
- 2018-12
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Density functional theory, Formate dehydrogenase, Molybdenum, QM/MM, Sulfur-shift mechanism
- in
- Journal of Biological Inorganic Chemistry
- volume
- 23
- issue
- 8
- pages
- 1243 - 1254
- publisher
- Springer
- external identifiers
-
- scopus:85053293022
- pmid:30173398
- ISSN
- 0949-8257
- DOI
- 10.1007/s00775-018-1608-y
- language
- English
- LU publication?
- yes
- id
- be2c9bd0-4862-4395-a5f3-d5154e8951ff
- date added to LUP
- 2018-10-23 12:28:10
- date last changed
- 2024-02-14 08:43:43
@article{be2c9bd0-4862-4395-a5f3-d5154e8951ff,
abstract = {{<p>Formate dehydrogenases (FDHs) are metalloenzymes that catalyse the reversible conversion of formate to carbon dioxide. Since such a process may be used to combat the greenhouse effect, FDHs have been extensively studied by experimental and theoretical methods. However, the reaction mechanism is still not clear; instead five putative mechanisms have been suggested. In this work, the reaction mechanism of FDH was studied by computational methods. Combined quantum mechanical and molecular mechanic (QM/MM) optimisations were performed to obtain the geometries. To get more accurate energies and obtain a detailed account of the surroundings, big-QM calculations with a very large (1121 atoms) QM region were performed. Our results indicate that the formate substrate does not coordinate directly to Mo when it enters the oxidised active site of the FDH, but instead resides in the second coordination sphere. The sulfido ligand abstracts a hydride ion from the substrate, giving a Mo(IV)–SH state and a thiocarbonate ion attached to Cys196. The latter releases CO<sub>2</sub> when the active site is oxidised back to the resting (Mo<sup>VI</sup>) state. This mechanism is supported by recent experimental studies.</p>}},
author = {{Dong, Geng and Ryde, Ulf}},
issn = {{0949-8257}},
keywords = {{Density functional theory; Formate dehydrogenase; Molybdenum; QM/MM; Sulfur-shift mechanism}},
language = {{eng}},
number = {{8}},
pages = {{1243--1254}},
publisher = {{Springer}},
series = {{Journal of Biological Inorganic Chemistry}},
title = {{Reaction mechanism of formate dehydrogenase studied by computational methods}},
url = {{http://dx.doi.org/10.1007/s00775-018-1608-y}},
doi = {{10.1007/s00775-018-1608-y}},
volume = {{23}},
year = {{2018}},
}