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Effect of the protein ligand in DMSO reductase studied by computational methods

Dong, Geng LU and Ryde, Ulf LU (2017) In Journal of Inorganic Biochemistry 171. p.45-51
Abstract

The DMSO reductase family is the largest and most diverse family of mononuclear molybdenum oxygen-atom-transfer proteins. Their active sites contain a Mo ion coordinated to two molybdopterin ligands, one oxo group in the oxidised state, and one additional, often protein-derived ligand. We have used density-functional theory to evaluate how the fourth ligand (serine, cysteine, selenocysteine, OH, O2–, SH, or S2–) affects the geometries, reaction mechanism, reaction energies, and reduction potentials of intermediates in the DMSO reductase reaction. Our results show that there are only small changes in the geometries of the reactant and product states, except from the elongation of the... (More)

The DMSO reductase family is the largest and most diverse family of mononuclear molybdenum oxygen-atom-transfer proteins. Their active sites contain a Mo ion coordinated to two molybdopterin ligands, one oxo group in the oxidised state, and one additional, often protein-derived ligand. We have used density-functional theory to evaluate how the fourth ligand (serine, cysteine, selenocysteine, OH, O2–, SH, or S2–) affects the geometries, reaction mechanism, reaction energies, and reduction potentials of intermediates in the DMSO reductase reaction. Our results show that there are only small changes in the geometries of the reactant and product states, except from the elongation of the Mo[sbnd]X bond as the ionic radius of X[dbnd]O, S, Se increases. The five ligands with a single negative charge gave an identical two-step reaction mechanism, in which DMSO first binds to the reduced active site, after which the S[sbnd]O bond is cleaved, concomitantly with the transfer of two electrons from Mo in a rate-determining second transition state. The five models gave similar activation energies of 69–85 kJ/mol, with SH giving the lowest barrier. In contrast, the O2– and S2– ligands gave much higher activation energies (212 and 168 kJ/mol) and differing mechanisms (a more symmetric intermediate for O2– and a one-step reaction without any intermediate for S2–). The high activation energies are caused by a less exothermic reaction energy, 13–25 kJ/mol, and by a more stable reactant state owing to the strong Mo[sbnd]O2– or Mo[sbnd]S2– bonds.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Arsenate oxidase, Density-functional theory, DMSO reductase, Ligand variation, Mo oxygen-atom-transfer proteins
in
Journal of Inorganic Biochemistry
volume
171
pages
7 pages
publisher
Elsevier
external identifiers
  • scopus:85016410761
  • wos:000402581000006
ISSN
0162-0134
DOI
10.1016/j.jinorgbio.2017.03.004
language
English
LU publication?
yes
id
928fc34d-7f19-46b6-8a69-d1dc5d9e52b3
date added to LUP
2017-04-11 11:11:00
date last changed
2018-01-07 11:58:55
@article{928fc34d-7f19-46b6-8a69-d1dc5d9e52b3,
  abstract     = {<p>The DMSO reductase family is the largest and most diverse family of mononuclear molybdenum oxygen-atom-transfer proteins. Their active sites contain a Mo ion coordinated to two molybdopterin ligands, one oxo group in the oxidised state, and one additional, often protein-derived ligand. We have used density-functional theory to evaluate how the fourth ligand (serine, cysteine, selenocysteine, OH<sup>−</sup>, O<sup>2–</sup>, SH<sup>−</sup>, or S<sup>2–</sup>) affects the geometries, reaction mechanism, reaction energies, and reduction potentials of intermediates in the DMSO reductase reaction. Our results show that there are only small changes in the geometries of the reactant and product states, except from the elongation of the Mo[sbnd]X bond as the ionic radius of X[dbnd]O, S, Se increases. The five ligands with a single negative charge gave an identical two-step reaction mechanism, in which DMSO first binds to the reduced active site, after which the S[sbnd]O bond is cleaved, concomitantly with the transfer of two electrons from Mo in a rate-determining second transition state. The five models gave similar activation energies of 69–85 kJ/mol, with SH<sup>−</sup> giving the lowest barrier. In contrast, the O<sup>2–</sup> and S<sup>2–</sup> ligands gave much higher activation energies (212 and 168 kJ/mol) and differing mechanisms (a more symmetric intermediate for O<sup>2–</sup> and a one-step reaction without any intermediate for S<sup>2–</sup>). The high activation energies are caused by a less exothermic reaction energy, 13–25 kJ/mol, and by a more stable reactant state owing to the strong Mo[sbnd]O<sup>2–</sup> or Mo[sbnd]S<sup>2–</sup> bonds.</p>},
  author       = {Dong, Geng and Ryde, Ulf},
  issn         = {0162-0134},
  keyword      = {Arsenate oxidase,Density-functional theory,DMSO reductase,Ligand variation,Mo oxygen-atom-transfer proteins},
  language     = {eng},
  month        = {06},
  pages        = {45--51},
  publisher    = {Elsevier},
  series       = {Journal of Inorganic Biochemistry},
  title        = {Effect of the protein ligand in DMSO reductase studied by computational methods},
  url          = {http://dx.doi.org/10.1016/j.jinorgbio.2017.03.004},
  volume       = {171},
  year         = {2017},
}