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

Journal Article · · Protein Science
DOI:https://doi.org/10.1002/pro.2768· OSTI ID:1221758
 [1];  [2];  [1];  [2];  [3];  [1]
  1. Univ. of Malta (Malta)
  2. Univ. of Leeds, Leeds (United Kingdom)
  3. Brookhaven National Lab. (BNL), Upton, NY (United States)
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. The 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.
Research Organization:
Brookhaven National Laboratory (BNL), Upton, NY (United States). Laser Electron Accelerator Facility (LEAF).
Sponsoring Organization:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22)
OSTI ID:
1221758
Report Number(s):
BNL--108388-2015-JA; KC0304030
Journal Information:
Protein Science, Journal Name: Protein Science; ISSN 0961-8368
Publisher:
The Protein SocietyCopyright Statement
Country of Publication:
United States
Language:
English

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A Review of the Catalytic Mechanism of Human Manganese Superoxide Dismutase journal January 2018
The first crystal structure of manganese superoxide dismutase from the genus Staphylococcus journal February 2018
Redox manipulation of the manganese metal in human manganese superoxide dismutase for neutron diffraction journal September 2018
Mechanism of Different Stereoisomeric Astaxanthin in Resistance to Oxidative Stress in Caenorhabditis elegans: Mechanism of astaxanthin stereoisomers… journal August 2016

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