NDLI: The structure of the Caenorhabditis elegans manganese superoxide dismutase MnSOD-3-azide complex.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Stewart, Emma E. Bonetta, Rosalin Hunter, Gary J. Hunter, Therese Trinh, Chi H. Cabelli, Diane E.
Description	Country affiliation: Malta Author Affiliation: Hunter GJ ( Department of Physiology and Biochemistry, Faculty of Medicine and Surgery, University of Malta, Msida, Malta.); Trinh CH ( Astbury Centre for Structural Molecular Biology, Institute of Molecular and Cellular Biology, University of Leeds, Leeds, United Kingdom.); Bonetta R ( Department of Physiology and Biochemistry, Faculty of Medicine and Surgery, University of Malta, Msida, Malta.); Stewart EE ( Astbury Centre for Structural Molecular Biology, Institute of Molecular and Cellular Biology, University of Leeds, Leeds, United Kingdom.); Cabelli DE ( Chemistry Department, Brookhaven National Laboratory, Upton, New York.); Hunter T ( Department of Physiology and Biochemistry, Faculty of Medicine and Surgery, University of Malta, Msida, Malta.)
Abstract	C. elegans MnSOD-3 has been implicated in the longevity pathway and its mechanism of catalysis is relevant to the aging process and carcinogenesis. The structures of MnSOD-3 provide unique crystallographic evidence of a dynamic region of the tetrameric interface (residues 41-54). We have determined the structure of the MnSOD-3-azide complex to 1.77-Å resolution. Analysis of this complex shows that the substrate analog, azide, binds end-on to the manganese center as a sixth ligand and that it ligates directly to a third and new solvent molecule also positioned within interacting distance to the His30 and Tyr34 residues of the substrate access funnel. This is the first structure of a eukaryotic MnSOD-azide complex that demonstrates the extended, uninterrupted hydrogen-bonded network that forms a proton relay incorporating three outer sphere solvent molecules, the substrate analog, the gateway residues, Gln142, and the solvent ligand. This configuration supports the formation and release of the hydrogen peroxide product in agreement with the 5-6-5 catalytic mechanism for MnSOD. The high product dissociation constant k4 of MnSOD-3 reflects low product inhibition making this enzyme efficient even at high levels of superoxide.
ISSN	09618368
e-ISSN	1469896X
Journal	Protein Science
Issue Number	11
Volume Number	24
Language	English
Publisher	Wiley-Blackwell (on behalf of The Protein Society)
Publisher Date	2015-11-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Azides Chemistry Caenorhabditis Elegans Proteins Superoxide Dismutase Metabolism Histidine Models, Molecular Protein Conformation Research Support, Non-u.s. Gov't Research Support, U.s. Gov't, Non-p.h.s. Discipline Biochemistry
Content Type	Text
Resource Type	Article
Subject	Medicine Molecular Biology Biochemistry

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