Isocyanide in Biochemistry? A Theoretical Investigation of the Electronic Effects and Energetics of Cyanide Ligand Protonation in [FeFe]-Hydrogenases
Greco, Claudio ; Bruschi, Maurizio ; Fantucci, Piercarlo ; Ryde, Ulf LU
and De Gioia, Luca
(2011)
In Chemistry: A European Journal
17(6).
p.1954-1965
- Abstract
- The presence of Fe-bound cyanide ligands in the active site of the proton-reducing enzymes [FeFe]-hydrogenases has led to the hypothesis that such Bronsted-Lowry bases could be protonated during the catalytic cycle, thus implying that hydrogen isocyanide (HNC) might have a relevant role in such crucial microbial metabolic paths. We present a hybrid quantum mechanical/molecular mechanical (QM/MM) study of the energetics of CN- protonation in the enzyme, and of the effects that cyanide protonation can have on [FeFe]-hydrogenase active sites. A detailed analysis of the electronic properties of the models and of the energy profile associated with H-2 evolution clearly shows that such protonation is dysfunctional for the catalytic process.... (More)
- The presence of Fe-bound cyanide ligands in the active site of the proton-reducing enzymes [FeFe]-hydrogenases has led to the hypothesis that such Bronsted-Lowry bases could be protonated during the catalytic cycle, thus implying that hydrogen isocyanide (HNC) might have a relevant role in such crucial microbial metabolic paths. We present a hybrid quantum mechanical/molecular mechanical (QM/MM) study of the energetics of CN- protonation in the enzyme, and of the effects that cyanide protonation can have on [FeFe]-hydrogenase active sites. A detailed analysis of the electronic properties of the models and of the energy profile associated with H-2 evolution clearly shows that such protonation is dysfunctional for the catalytic process. However, the inclusion of the protein matrix surrounding the active site in our QM/MM models allowed us to demonstrate that the amino acid environment was finely selected through evolution, specifically to lower the Bronsted-Lowry basicity of the cyanide ligands. In fact, the conserved hydrogen-bonding network formed by these ligands and the neighboring amino acid residues is able to impede CN- protonation, as shown by the fact that the isocyanide forms of [FeFe]-hydrogenases do not correspond to stationary points on the enzyme QM/MM potential-energy surface. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1868555
- author
- Greco, Claudio
; Bruschi, Maurizio
; Fantucci, Piercarlo
; Ryde, Ulf
LU
and De Gioia, Luca
- organization
- publishing date
- 2011
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- density functional calculations, hydrogenases, isocyanide ligands, protonation, QM/MM methods
- in
- Chemistry: A European Journal
- volume
- 17
- issue
- 6
- pages
- 1954 - 1965
- publisher
- Wiley-Blackwell
- external identifiers
-
- wos:000287787100028
- scopus:79551468716
- ISSN
- 1521-3765
- DOI
- 10.1002/chem.201001493
- 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
- 1f2c67f3-797b-45ef-b1ae-4d6bd55bfcda (old id 1868555)
- date added to LUP
- 2016-04-01 14:35:47
- date last changed
- 2025-10-14 09:50:22
@article{1f2c67f3-797b-45ef-b1ae-4d6bd55bfcda,
abstract = {{The presence of Fe-bound cyanide ligands in the active site of the proton-reducing enzymes [FeFe]-hydrogenases has led to the hypothesis that such Bronsted-Lowry bases could be protonated during the catalytic cycle, thus implying that hydrogen isocyanide (HNC) might have a relevant role in such crucial microbial metabolic paths. We present a hybrid quantum mechanical/molecular mechanical (QM/MM) study of the energetics of CN- protonation in the enzyme, and of the effects that cyanide protonation can have on [FeFe]-hydrogenase active sites. A detailed analysis of the electronic properties of the models and of the energy profile associated with H-2 evolution clearly shows that such protonation is dysfunctional for the catalytic process. However, the inclusion of the protein matrix surrounding the active site in our QM/MM models allowed us to demonstrate that the amino acid environment was finely selected through evolution, specifically to lower the Bronsted-Lowry basicity of the cyanide ligands. In fact, the conserved hydrogen-bonding network formed by these ligands and the neighboring amino acid residues is able to impede CN- protonation, as shown by the fact that the isocyanide forms of [FeFe]-hydrogenases do not correspond to stationary points on the enzyme QM/MM potential-energy surface.}},
author = {{Greco, Claudio and Bruschi, Maurizio and Fantucci, Piercarlo and Ryde, Ulf and De Gioia, Luca}},
issn = {{1521-3765}},
keywords = {{density functional calculations; hydrogenases; isocyanide ligands; protonation; QM/MM methods}},
language = {{eng}},
number = {{6}},
pages = {{1954--1965}},
publisher = {{Wiley-Blackwell}},
series = {{Chemistry: A European Journal}},
title = {{Isocyanide in Biochemistry? A Theoretical Investigation of the Electronic Effects and Energetics of Cyanide Ligand Protonation in [FeFe]-Hydrogenases}},
url = {{http://dx.doi.org/10.1002/chem.201001493}},
doi = {{10.1002/chem.201001493}},
volume = {{17}},
year = {{2011}},
}