Description
Experimental Technique/Method:X-RAY DIFFRACTION
Resolution:2.35
Classification:oxidoreductase/chaperone
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
DOI:10.2210/pdb5u9m/pdb
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.
Resolution:2.35
Classification:oxidoreductase/chaperone
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
DOI:10.2210/pdb5u9m/pdb
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.
| Date made available | 2017 |
|---|---|
| Publisher | RCSB-PDB |