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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
; and
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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 (ACS)
external identifiers
  • pmid:18251539
  • wos:000253355500024
  • scopus:40549129032
  • pmid:18251539
ISSN
1520-5207
DOI
10.1021/jp710038s
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
211f306d-5f90-489a-bc36-ef50a00a4841 (old id 1042201)
date added to LUP
2016-04-01 14:29:50
date last changed
2020-11-22 04:18:04
@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 (ACS)},
  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},
  doi          = {10.1021/jp710038s},
  volume       = {112},
  year         = {2008},
}