Enhancement of Oxidative Reaction by the Intramolecular Electron Transfer between the Coordinated Redox-Active Metal Ions in SOD1

J Phys Chem B. 2020 Mar 19;124(11):2116-2123. doi: 10.1021/acs.jpcb.9b11807. Epub 2020 Mar 10.

Abstract

The denatured Cu, Zn superoxide dismutase (SOD1) has the pro-oxidant activity that is suggested to be related with the pathogenesis of amyotrophic lateral sclerosis (ALS). We showed from the changes in the coordinated metal ions that the Cu ion in the Cu-binding site is the catalytic site of the pro-oxidant activity, and a redox-active metal ion in the Zn-binding site has the auxiliary function to enhance the pro-oxidant activity. The auxiliary function is suggested to arise from the intramolecular electron transfer between the coordinated metal ions in the denatured SOD1. The oxidation/reduction cycle of Cu in the Cu-binding site is assisted with changing the oxidation state of a metal ion in the Zn-binding site. The magnitude of the toxicity of the denatured SOD1 is discussed based on the ability of the auxiliary function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyotrophic Lateral Sclerosis*
  • Electrons*
  • Humans
  • Ions
  • Mutation
  • Oxidation-Reduction
  • Oxidative Stress
  • Superoxide Dismutase / metabolism
  • Superoxide Dismutase-1 / genetics
  • Superoxide Dismutase-1 / metabolism

Substances

  • Ions
  • SOD1 protein, human
  • Superoxide Dismutase
  • Superoxide Dismutase-1