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On the role of the axial ligand in heme proteins: a theoretical study

Rydberg, Patrik LU ; Sigfridsson, Emma and Ryde, Ulf LU (2004) In Journal of Biological Inorganic Chemistry 9(2). p.203-223
Abstract
We present a systematic investigation of how the axial ligand in heme proteins influences the geometry, electronic structure, and spin states of the active site, and the energies of the reaction cycles. Using the density functional B3LYP method and medium-sized basis sets, we have compared models with His, His+Asp, Cys, Tyr, and Tyr+Arg as found in myoglobin and hemoglobin, peroxidases, cytochrome P450, and heme catalases, respectively. We have studied 12 reactants and intermediates of the reaction cycles of these enzymes, including complexes with H2O, OH-, O2-, CH3OH, O-2, H2O2, and HO2- in various formal oxidation states of the iron ion (II to V). The results show that His gives similar to0.6 V higher reduction potentials than the other... (More)
We present a systematic investigation of how the axial ligand in heme proteins influences the geometry, electronic structure, and spin states of the active site, and the energies of the reaction cycles. Using the density functional B3LYP method and medium-sized basis sets, we have compared models with His, His+Asp, Cys, Tyr, and Tyr+Arg as found in myoglobin and hemoglobin, peroxidases, cytochrome P450, and heme catalases, respectively. We have studied 12 reactants and intermediates of the reaction cycles of these enzymes, including complexes with H2O, OH-, O2-, CH3OH, O-2, H2O2, and HO2- in various formal oxidation states of the iron ion (II to V). The results show that His gives similar to0.6 V higher reduction potentials than the other ligands. In particular, it is harder to reduce and protonate the O-2 complex with His than with the other ligands, in accordance with the O-2 carrier function of globins and the oxidative chemistry of the other proteins. For most properties, the trend Cys<Tyr<Tyr+Arg<His+Asp<His is found, reflecting the donor capacity of the various ligands. Thus, it is easier to reduce compound I with a His+Asp ligand than with a Cys ligand, in accordance with the one-electron chemistry of peroxidases and the hydroxylation reactions of cytochromes P450. However, the Tyr complexes have an unusually low affinity for all neutral ligands, giving them a slightly enhanced driving force in the oxidation of H2O2 by compound I. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Biological Inorganic Chemistry
volume
9
issue
2
pages
203 - 223
publisher
Springer
external identifiers
  • wos:000189274500010
  • pmid:14727167
  • scopus:1542620864
ISSN
1432-1327
DOI
10.1007/s00775-003-0515-y
language
English
LU publication?
yes
id
3ee040ef-1aed-40be-acdd-55b332ed60bd (old id 139701)
date added to LUP
2007-07-17 13:45:35
date last changed
2017-11-26 03:20:27
@article{3ee040ef-1aed-40be-acdd-55b332ed60bd,
  abstract     = {We present a systematic investigation of how the axial ligand in heme proteins influences the geometry, electronic structure, and spin states of the active site, and the energies of the reaction cycles. Using the density functional B3LYP method and medium-sized basis sets, we have compared models with His, His+Asp, Cys, Tyr, and Tyr+Arg as found in myoglobin and hemoglobin, peroxidases, cytochrome P450, and heme catalases, respectively. We have studied 12 reactants and intermediates of the reaction cycles of these enzymes, including complexes with H2O, OH-, O2-, CH3OH, O-2, H2O2, and HO2- in various formal oxidation states of the iron ion (II to V). The results show that His gives similar to0.6 V higher reduction potentials than the other ligands. In particular, it is harder to reduce and protonate the O-2 complex with His than with the other ligands, in accordance with the O-2 carrier function of globins and the oxidative chemistry of the other proteins. For most properties, the trend Cys&lt;Tyr&lt;Tyr+Arg&lt;His+Asp&lt;His is found, reflecting the donor capacity of the various ligands. Thus, it is easier to reduce compound I with a His+Asp ligand than with a Cys ligand, in accordance with the one-electron chemistry of peroxidases and the hydroxylation reactions of cytochromes P450. However, the Tyr complexes have an unusually low affinity for all neutral ligands, giving them a slightly enhanced driving force in the oxidation of H2O2 by compound I.},
  author       = {Rydberg, Patrik and Sigfridsson, Emma and Ryde, Ulf},
  issn         = {1432-1327},
  language     = {eng},
  number       = {2},
  pages        = {203--223},
  publisher    = {Springer},
  series       = {Journal of Biological Inorganic Chemistry},
  title        = {On the role of the axial ligand in heme proteins: a theoretical study},
  url          = {http://dx.doi.org/10.1007/s00775-003-0515-y},
  volume       = {9},
  year         = {2004},
}