Copper-zinc superoxide dismutase is activated through a sulfenic acid intermediate at a copper ion entry site.
J Biol Chem
; 292(29): 12025-12040, 2017 07 21.
Article
in En
| MEDLINE
| ID: mdl-28533431
ABSTRACT
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Superoxide Dismutase
/
Models, Molecular
/
Protein Processing, Post-Translational
/
Molecular Chaperones
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Copper
/
Cystine
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Saccharomyces cerevisiae Proteins
Limits:
Humans
Language:
En
Journal:
J Biol Chem
Year:
2017
Type:
Article