5U9M : Copper-Zinc Superoxide Dismutase is Activated through a Sulfenic Acid Intermediate at a Copper-ion Entry Site



Experimental Technique/Method:X-RAY DIFFRACTION
Release Date:2017-05-31
Deposition Date:2016-12-16
Revision Date:2017-06-07#2017-08-02
Molecular Weight:85926.41
Macromolecule Type:Protein
Residue Count:802
Atom Site Count:5737

Metallochaperones are a diverse family of trafficking molecules that provide metal ions to protein targets for use as cofactors. The copper chaperone for superoxide dismutase (Ccs1) activates immature copper-zinc superoxide dismutase (Sod1) by delivering copper and facilitating the oxidation of the Sod1 intramolecular disulfide bond. Here, we present structural, spectroscopic, and cell-based data supporting a novel copper-induced mechanism for Sod1 activation. Ccs1 binding exposes an electropositive cavity and proposed "entry site" for copper ion delivery on immature Sod1. Copper-mediated sulfenylation leads to a sulfenic acid intermediate that eventually resolves to form the Sod1 disulfide bond with concomitant release of copper into the Sod1 active site. Sod1 is the predominant disulfide bond-requiring enzyme in the cytoplasm, and this copper-induced mechanism of disulfide bond formation obviates the need for a thiol/disulfide oxidoreductase in that compartment.
Date made available2017

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