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HERO ID
6793470
Reference Type
Journal Article
Title
Crystal structure of nitrated human manganese superoxide dismutase: Mechanism of inactivation
Author(s)
Quint, P; Reutzel, R; Mikulski, R; Mckenna, R; Silverman, DN; ,
Year
2006
Is Peer Reviewed?
Yes
Journal
Free Radical Biology and Medicine
ISSN:
0891-5849
EISSN:
1873-4596
Publisher
ELSEVIER SCIENCE INC
Location
NEW YORK
Volume
40
Issue
3
Page Numbers
453-458
Language
English
PMID
16443160
DOI
10.1016/j.freeradbiomed.2005.08.045
Web of Science Id
WOS:000235374600011
Abstract
A cellular consequence of the reaction of superoxide and nitric oxide is enhanced peroxynitrite levels. Reaction of peroxynitrite with manganese superoxide dismutase (MnSOD) causes nitration of the active-site residue Tyr34 and nearly complete inhibition of catalysis. We report the crystal structures at 2.4 angstrom resolution of human MnSOD nitrated by peroxynitrite and the unmodified MnSOD. A comparison of these structures showed no significant conformational changes of active-site residues or solvent displacement. The side chain of 3-nitrotyrosine 34 had a single conformation that extended toward the manganese with O1 of the nitro group within hydrogen-bonding distance (3.1 angstrom) of N epsilon 2 of the second-shell ligand Glnl43. Also, nitration of Tyr34 caused a weakening, as evidenced by the lengthening, of a hydrogen bond between its phenolic OH and Gln143, part of an extensive hydrogen-bond network in the active site. Inhibition of catalysis can be attributed to a steric effect of 3-nitrotyrosine 34 that impedes substrate access and binding, and alteration of the hydrogen-bond network that supports proton transfer in catalysis. It is also possible that an electrostatic effect of the nitro group has altered the finely tuned redox potential necessary for efficient catalysis, although the redox potential of nitrated MnSOD has not been measured. (c) 2005 Elsevier Inc. All rights reserved.
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