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Effect of covalent links on the structure, spectra, and redox properties of myeloperoxidase - A density functional study.

Devarajan, Ajitha LU ; Gaenko, Alexander LU and Ryde, Ulf LU (2008) In Journal of Inorganic Biochemistry 102. p.1549-1557
Abstract
The enzyme myeloperoxidase shows several unusual properties compared to other peroxidases, e.g. a red-shifted absorption spectrum and a peroxidase activity towards chloride. It has been suggested that this is caused by the unusual covalent links between the heme group and the surrounding protein, but whether it is caused by the two ester links to Glu-242 and Asp-94 or the sulfonium ion linkage to Met-243 is unclear. To investigate these suggestions, we have used density functional theory to study the structure, spectra, and reduction potential of 25 models of myeloperoxidase in the reduced (Fe(II)) and oxidized (Fe(III)) states, as well as in the compound I (formally Fe(V)O) and II (Fe(IV)O or Fe(IV)OH) states, using appropriate models of... (More)
The enzyme myeloperoxidase shows several unusual properties compared to other peroxidases, e.g. a red-shifted absorption spectrum and a peroxidase activity towards chloride. It has been suggested that this is caused by the unusual covalent links between the heme group and the surrounding protein, but whether it is caused by the two ester links to Glu-242 and Asp-94 or the sulfonium ion linkage to Met-243 is unclear. To investigate these suggestions, we have used density functional theory to study the structure, spectra, and reduction potential of 25 models of myeloperoxidase in the reduced (Fe(II)) and oxidized (Fe(III)) states, as well as in the compound I (formally Fe(V)O) and II (Fe(IV)O or Fe(IV)OH) states, using appropriate models of the linkages to the Asp, Glu, and Met residues (including the back-bone connection between Glu-242 and Met-243) in varying combinations. The calculated spectral shifts indicate that both the ester and sulfonium linkages play a role in the spectral shift. On the other hand, the sulfonium linkage seems to be mainly responsible for the high positive reduction potential for the both ferric/ferrous and compound I/II couples of myeloperoxidase. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Mammalian peroxidases, Electronic spectra, Reduction potentials, Compound II, Time-dependent density functional theory
in
Journal of Inorganic Biochemistry
volume
102
pages
1549 - 1557
publisher
Elsevier
external identifiers
  • pmid:18331758
  • wos:000258012000001
  • scopus:46749157484
ISSN
1873-3344
DOI
10.1016/j.jinorgbio.2008.01.031
language
English
LU publication?
yes
id
71016228-1a82-40dd-8ca9-55d1e34cc78f (old id 1052650)
date added to LUP
2008-05-23 09:11:11
date last changed
2017-01-01 05:42:06
@article{71016228-1a82-40dd-8ca9-55d1e34cc78f,
  abstract     = {The enzyme myeloperoxidase shows several unusual properties compared to other peroxidases, e.g. a red-shifted absorption spectrum and a peroxidase activity towards chloride. It has been suggested that this is caused by the unusual covalent links between the heme group and the surrounding protein, but whether it is caused by the two ester links to Glu-242 and Asp-94 or the sulfonium ion linkage to Met-243 is unclear. To investigate these suggestions, we have used density functional theory to study the structure, spectra, and reduction potential of 25 models of myeloperoxidase in the reduced (Fe(II)) and oxidized (Fe(III)) states, as well as in the compound I (formally Fe(V)O) and II (Fe(IV)O or Fe(IV)OH) states, using appropriate models of the linkages to the Asp, Glu, and Met residues (including the back-bone connection between Glu-242 and Met-243) in varying combinations. The calculated spectral shifts indicate that both the ester and sulfonium linkages play a role in the spectral shift. On the other hand, the sulfonium linkage seems to be mainly responsible for the high positive reduction potential for the both ferric/ferrous and compound I/II couples of myeloperoxidase.},
  author       = {Devarajan, Ajitha and Gaenko, Alexander and Ryde, Ulf},
  issn         = {1873-3344},
  keyword      = {Mammalian peroxidases,Electronic spectra,Reduction potentials,Compound II,Time-dependent density functional theory},
  language     = {eng},
  pages        = {1549--1557},
  publisher    = {Elsevier},
  series       = {Journal of Inorganic Biochemistry},
  title        = {Effect of covalent links on the structure, spectra, and redox properties of myeloperoxidase - A density functional study.},
  url          = {http://dx.doi.org/10.1016/j.jinorgbio.2008.01.031},
  volume       = {102},
  year         = {2008},
}