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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)
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author
organization
publishing date
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
John Wiley & Sons
external identifiers
  • wos:000287787100028
  • scopus:79551468716
ISSN
1521-3765
DOI
10.1002/chem.201001493
language
English
LU publication?
yes
id
1f2c67f3-797b-45ef-b1ae-4d6bd55bfcda (old id 1868555)
date added to LUP
2011-04-19 12:11:23
date last changed
2017-11-12 03:46:35
@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},
  keyword      = {density functional calculations,hydrogenases,isocyanide ligands,protonation,QM/MM methods},
  language     = {eng},
  number       = {6},
  pages        = {1954--1965},
  publisher    = {John Wiley & Sons},
  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},
  volume       = {17},
  year         = {2011},
}