Winkler, Duane D.

Permanent URI for this collectionhttps://hdl.handle.net/10735.1/5913

Duane Winkler is an Assistant Professor in the Department of Biological Sciences. In 2016, Dr. Winkler received a five-year $1.3 million grant from the National Institute of General Medical Sciences to study the biological mechanisms that underlie Alzheimer's disease and other neurodegenerative disorders in order to develop new treatment strategies.

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Browsing Winkler, Duane D. by Subject "Copper ions"

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    Copper-Zinc Superoxide Dismutase Is Activated through a Sulfenic Acid Intermediate at a Copper Ion Entry Site
    (American Society for Biochemistry and Molecular Biology Inc, 2018-08-20) Fetherolf, M. M.; Boyd, Stefanie D.; Taylor, A. B.; Kim, H. J.; Wohlschlegel, J. A.; Blackburn, N. J.; Hart, P. J.; Winge, D. R.; Winkler, Duane D.; Boyd, Stefanie D.; Winkler, Duane D.
    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.

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