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Protonation of the proximal histidine ligand in heme peroxidases.

Heimdal, Jimmy LU ; Rydberg, Patrik LU and Ryde, Ulf LU (2008) In The Journal of Physical Chemistry Part B 112(8). p.2501-2510
Abstract
The heme peroxidases have a histidine group as the axial ligand of iron. This ligand forms a hydrogen bond to an aspartate carboxylate group by the other nitrogen atom in the side chain. The aspartate is not present in the globins and it has been suggested that it gives an imidazolate character to the histidine ligand. Quantum chemical calculations have indicated that the properties of the heme site strongly depend on the position of the proton in this hydrogen bond. Therefore, we have studied the location of this proton in all intermediates in the reaction mechanism, using a set of different quantum mechanical and combined experimental and computational methods. Quantum refinements of a crystal structure of the resting FeIII state in... (More)
The heme peroxidases have a histidine group as the axial ligand of iron. This ligand forms a hydrogen bond to an aspartate carboxylate group by the other nitrogen atom in the side chain. The aspartate is not present in the globins and it has been suggested that it gives an imidazolate character to the histidine ligand. Quantum chemical calculations have indicated that the properties of the heme site strongly depend on the position of the proton in this hydrogen bond. Therefore, we have studied the location of this proton in all intermediates in the reaction mechanism, using a set of different quantum mechanical and combined experimental and computational methods. Quantum refinements of a crystal structure of the resting FeIII state in yeast cytochrome c peroxidase show that the geometric differences of the two states are so small that it cannot be unambiguously decided where the proton is in the crystal structure. Vacuum calculations indicate that the position of the proton is sensitive to the surroundings and to the side chains of the porphyrin ring. Combined quantum and molecular mechanics (QM/MM) calculations indicate that the proton prefers to reside on the His ligand in all states in the reaction mechanism of the peroxidases. QM/MM free energy perturbations confirm these results, but reduce the energy difference between the two states to 12-44 kJ/mol. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
The Journal of Physical Chemistry Part B
volume
112
issue
8
pages
2501 - 2510
publisher
The American Chemical Society
external identifiers
  • pmid:18251539
  • wos:000253355500024
  • scopus:40549129032
ISSN
1520-5207
DOI
10.1021/jp710038s
language
English
LU publication?
yes
id
211f306d-5f90-489a-bc36-ef50a00a4841 (old id 1042201)
date added to LUP
2008-03-25 14:46:10
date last changed
2017-07-02 04:07:50
@article{211f306d-5f90-489a-bc36-ef50a00a4841,
  abstract     = {The heme peroxidases have a histidine group as the axial ligand of iron. This ligand forms a hydrogen bond to an aspartate carboxylate group by the other nitrogen atom in the side chain. The aspartate is not present in the globins and it has been suggested that it gives an imidazolate character to the histidine ligand. Quantum chemical calculations have indicated that the properties of the heme site strongly depend on the position of the proton in this hydrogen bond. Therefore, we have studied the location of this proton in all intermediates in the reaction mechanism, using a set of different quantum mechanical and combined experimental and computational methods. Quantum refinements of a crystal structure of the resting FeIII state in yeast cytochrome c peroxidase show that the geometric differences of the two states are so small that it cannot be unambiguously decided where the proton is in the crystal structure. Vacuum calculations indicate that the position of the proton is sensitive to the surroundings and to the side chains of the porphyrin ring. Combined quantum and molecular mechanics (QM/MM) calculations indicate that the proton prefers to reside on the His ligand in all states in the reaction mechanism of the peroxidases. QM/MM free energy perturbations confirm these results, but reduce the energy difference between the two states to 12-44 kJ/mol.},
  author       = {Heimdal, Jimmy and Rydberg, Patrik and Ryde, Ulf},
  issn         = {1520-5207},
  language     = {eng},
  number       = {8},
  pages        = {2501--2510},
  publisher    = {The American Chemical Society},
  series       = {The Journal of Physical Chemistry Part B},
  title        = {Protonation of the proximal histidine ligand in heme peroxidases.},
  url          = {http://dx.doi.org/10.1021/jp710038s},
  volume       = {112},
  year         = {2008},
}