5U9M

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

Summary for 5U9M

• Entry DOI: 10.2210/pdb5u9m/pdb
• Descriptor: Superoxide dismutase [Cu-Zn], Superoxide dismutase 1 copper chaperone, ZINC ION, ... (4 entities in total)
• Functional Keywords: oxidoreductase-chaperone complex, cu-zn superoxide dismutase, metallochaperone, oxidoreductase/chaperone
• Biological source: Homo sapiens (Human); More
• Cellular location: Cytoplasm : P00441 P40202
• Total number of polymer chains: 4
• Total formula weight: 85926.40

Authors

Taylor, A.B.,Hart, P.J.,Winkler, D.D. (deposition date: 2016-12-16, release date: 2017-05-31, Last modification date: 2024-10-23)

Primary citation

Fetherolf, M.M.,Boyd, S.D.,Taylor, A.B.,Kim, H.J.,Wohlschlegel, J.A.,Blackburn, N.J.,Hart, P.J.,Winge, D.R.,Winkler, D.D.
Copper-zinc superoxide dismutase is activated through a sulfenic acid intermediate at a copper ion entry site.
J. Biol. Chem., 292:12025-12040, 2017

PubMed 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.

PubMed: 28533431
DOI: 10.1074/jbc.M117.775981

Experimental method

X-RAY DIFFRACTION (2.35 Å)