Copper-Zinc Superoxide Dismutase Is Activated through a Sulfenic Acid Intermediate at a Copper Ion Entry Site

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dc.contributor.authorFetherolf, M. M.en_US
dc.contributor.authorBoyd, Stefanie D.en_US
dc.contributor.authorTaylor, A. B.en_US
dc.contributor.authorKim, H. J.en_US
dc.contributor.authorWohlschlegel, J. A.en_US
dc.contributor.authorBlackburn, N. J.en_US
dc.contributor.authorHart, P. J.en_US
dc.contributor.authorWinge, D. R.en_US
dc.contributor.authorWinkler, Duane D.en_US
dc.contributor.utdAuthorBoyd, Stefanie D.en_US
dc.contributor.utdAuthorWinkler, Duane D.en_US
dc.date.accessioned2018-08-20T16:35:16Z
dc.date.available2018-08-20T16:35:16Z
dc.date.created2017-05-22en_US
dc.date.issued2018-08-20
dc.description.abstractMetallochaperones 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.en_US
dc.description.departmentSchool of Natural Sciences and Mathematicsen_US
dc.description.sponsorshipThis work was supported in part by National Institutes of Health Grants R01 GM110755, R01 GM054803, R01 NS39112, R01 GM112763, and R01 GM120252; United States Department of Veterans Affairs Merit Review Award I01 BX002580; National Institutes of Health Grant P41 GM103403 and United States Department of Energy Grant DE-AC02-06CH11357; San Antonio Cancer Institute Grant P30 CA054174; United States Department of Energy, Office of Science, Office of Basic Energy Sciences under Contract DE-AC02-76SF00515;en_US
dc.identifier.bibliographicCitationFetherolf, M. M., S. D. Boyd, A. B. Taylor, H. J. Kim, et al. 2017. "Copper-zinc superoxide dismutase is activated through a sulfenic acid intermediate at a copper ion entry site; 28533431." Journal of Biological Chemistry 292(29), doi:10.1074/jbc.M117.775981en_US
dc.identifier.issn0021-9258en_US
dc.identifier.issue29en_US
dc.identifier.urihttp://hdl.handle.net/10735.1/6004
dc.identifier.volume292en_US
dc.language.isoenen_US
dc.publisherAmerican Society for Biochemistry and Molecular Biology Incen_US
dc.relation.urihttp://dx.doi.org/10.1074/jbc.M117.775981
dc.rights© 2017, American Society for Biochemistry and Molecular Biology Inc. All rights reserved.en_US
dc.sourceJournal of Biological Chemistry
dc.subjectMolecular chaperonesen_US
dc.subjectCytologyen_US
dc.subjectEnzymesen_US
dc.subjectMetal ionsen_US
dc.subjectMetalsen_US
dc.subjectOxygenen_US
dc.subjectSulfur compoundsen_US
dc.subjectZincen_US
dc.subjectOxidoreductasesen_US
dc.subjectSuperoxide dismutaseen_US
dc.subjectCopperen_US
dc.subjectCopper ionsen_US
dc.subjectCysteineen_US
dc.subjectOxidoreductasesen_US
dc.subjectSulfenic acidsen_US
dc.subjectSuperoxide dismutaseen_US
dc.subjectApoenzymesen_US
dc.subjectCcs1 protein, s cerevisiaeen_US
dc.subjectCystineen_US
dc.subjectLigandsen_US
dc.subjectLys7 protein, S cerevisiaeen_US
dc.subjectRecombinant Proteinsen_US
dc.subjectSaccharomyces cerevisiaeen_US
dc.subjectCytoplasmen_US
dc.subjectEnzyme activationen_US
dc.subjectIon Transporten_US
dc.subjectProtein protein interactionsen_US
dc.subjectSpectrum analysisen_US
dc.subjectStructure-activity relationships (Biochemistry)en_US
dc.subjectAmino Acid Substitutionen_US
dc.subjectBinding Sitesen_US
dc.subjectChemistryen_US
dc.subjectEnzyme Stabilityen_US
dc.subjectGeneticsen_US
dc.subjectHumansen_US
dc.subjectMetabolismen_US
dc.subjectModels, Molecularen_US
dc.subjectMutationen_US
dc.subjectOxidation -Reductionen_US
dc.subjectProtein Conformationen_US
dc.subjectProtein Domainsen_US
dc.subjectMutagenesis, Site-Directeden_US
dc.subjectCrystallography, X-Rayen_US
dc.titleCopper-Zinc Superoxide Dismutase Is Activated through a Sulfenic Acid Intermediate at a Copper Ion Entry Siteen_US
dc.type.genrearticleen_US

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