Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

Structure of reduced and oxidized manganese superoxide dismutase: A combined computational and experimental approach

Rulisek, Lubomir LU and Ryde, Ulf LU orcid (2006) In The Journal of Physical Chemistry Part B 110(23). p.11511-11518
Abstract
Manganese superoxide dismutases catalyze the disproportionation of the superoxide radical anion to molecular oxygen and hydrogen peroxide. Recently, atomic-resolution crystal structures of the reduced and oxidized enzymes have been reported. They show an active site with the manganese ion bound to one aspartate, three histidine residues, and a solvent molecule. In this paper, we combine crystallographic refinement with quantum mechanical methods to show that the solvent ligand is undoubtedly a water molecule in the reduced state. However, the putative oxidized structure is to a large extent reduced during data collection, so that it contains a mixture of the Mn2+ and Mn3+ structure. The crystal structures show that the Mn-bound solvent... (More)
Manganese superoxide dismutases catalyze the disproportionation of the superoxide radical anion to molecular oxygen and hydrogen peroxide. Recently, atomic-resolution crystal structures of the reduced and oxidized enzymes have been reported. They show an active site with the manganese ion bound to one aspartate, three histidine residues, and a solvent molecule. In this paper, we combine crystallographic refinement with quantum mechanical methods to show that the solvent ligand is undoubtedly a water molecule in the reduced state. However, the putative oxidized structure is to a large extent reduced during data collection, so that it contains a mixture of the Mn2+ and Mn3+ structure. The crystal structures show that the Mn-bound solvent molecule accepts a hydrogen bond from the side chain of the conserved Gln-146 residue. If the solvent ligand is water, then this could lead to a steric clash, but it is avoided by the plane of water molecule forming an angle of 72 degrees to the Mn-O bond. Such a conformation is also found outside the enzyme, giving a minimal destabilization of the reduced state. We show by molecular dynamics simulations that the suggested Mn2+-(HO)-O-2 and Mn3+OH- structures are stable. Moreover, we show that the superoxide substrate may bind both in the first coordination sphere of the Mn ion, opposite to the aspartate ligand, or in the second sphere, close to the conserved Tyr-34 and His-30 residues, similar to 5 angstrom from Mn. However, the second-sphere structures are not stable in long molecular dynamics simulations. We see no difference in the coordination between the reduced and the oxidized states of the enzyme. (Less)
Please use this url to cite or link to this publication:
author
and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
The Journal of Physical Chemistry Part B
volume
110
issue
23
pages
11511 - 11518
publisher
The American Chemical Society (ACS)
external identifiers
  • wos:000238102800071
  • scopus:33745727307
ISSN
1520-5207
DOI
10.1021/jp057295t
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
b929cc92-de3e-4d5c-9fd4-f089c9de0b8e (old id 406777)
date added to LUP
2016-04-01 16:09:13
date last changed
2021-10-03 04:14:51
@article{b929cc92-de3e-4d5c-9fd4-f089c9de0b8e,
  abstract     = {Manganese superoxide dismutases catalyze the disproportionation of the superoxide radical anion to molecular oxygen and hydrogen peroxide. Recently, atomic-resolution crystal structures of the reduced and oxidized enzymes have been reported. They show an active site with the manganese ion bound to one aspartate, three histidine residues, and a solvent molecule. In this paper, we combine crystallographic refinement with quantum mechanical methods to show that the solvent ligand is undoubtedly a water molecule in the reduced state. However, the putative oxidized structure is to a large extent reduced during data collection, so that it contains a mixture of the Mn2+ and Mn3+ structure. The crystal structures show that the Mn-bound solvent molecule accepts a hydrogen bond from the side chain of the conserved Gln-146 residue. If the solvent ligand is water, then this could lead to a steric clash, but it is avoided by the plane of water molecule forming an angle of 72 degrees to the Mn-O bond. Such a conformation is also found outside the enzyme, giving a minimal destabilization of the reduced state. We show by molecular dynamics simulations that the suggested Mn2+-(HO)-O-2 and Mn3+OH- structures are stable. Moreover, we show that the superoxide substrate may bind both in the first coordination sphere of the Mn ion, opposite to the aspartate ligand, or in the second sphere, close to the conserved Tyr-34 and His-30 residues, similar to 5 angstrom from Mn. However, the second-sphere structures are not stable in long molecular dynamics simulations. We see no difference in the coordination between the reduced and the oxidized states of the enzyme.},
  author       = {Rulisek, Lubomir and Ryde, Ulf},
  issn         = {1520-5207},
  language     = {eng},
  number       = {23},
  pages        = {11511--11518},
  publisher    = {The American Chemical Society (ACS)},
  series       = {The Journal of Physical Chemistry Part B},
  title        = {Structure of reduced and oxidized manganese superoxide dismutase: A combined computational and experimental approach},
  url          = {http://dx.doi.org/10.1021/jp057295t},
  doi          = {10.1021/jp057295t},
  volume       = {110},
  year         = {2006},
}