Inactivation of copper, zinc superoxide dismutase by H2O2 : mechanism of protection.

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Goldstone AB, Liochev SI, Fridovich I

Inactivation of copper, zinc superoxide dismutase by H2O2 : mechanism of protection.

Free Radic Biol Med. 2006 Dec 15;41(12):1860-3. Epub 2006 Sep 19.

PubMed ID

17157188 [ View in PubMed

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Abstract

Cu,Zn SOD is known to be inactivated by HO(2)(-) and to be protected against that inactivation by a number of small molecules including formate, imidazole, and urate. This inactivation has been shown to be due to oxidation of a ligand field histidine residue by a bound oxidant formed by reaction of the active site Cu(II) with HO(2)(-). We now report that protective actions of both formate and NADH increase as the pH was raised in the range 8.0-9.5. This is taken to indicate increased accessibility of the Cu site with rising pH and/or increased reactivity of the bound oxidant toward exogeneous substrates at high pH. Formate appears to act as a sacrificial substrate that protects by competing with the endogenous histidine residue for reaction with the bound oxidant, or that repairs the damage by reducing the histidyl radical intermediate. The same is likely also true of NADH.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
NADH	Heme oxygenase 2	Protein	Humans	Unknown	Not Available	Details