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dc.contributor.authorGaffney, Dominique O
dc.contributor.authorJennings, Erin Q
dc.contributor.authorAnderson, Colin C
dc.contributor.authorMarentette, John O
dc.contributor.authorShi, Taoda
dc.contributor.authorSchou Oxvig, Anne-Mette
dc.contributor.authorStreeter, Matthew D
dc.contributor.authorJohannsen, Mogens
dc.contributor.authorSpiegel, David A
dc.contributor.authorChapman, Eli
dc.contributor.authorRoede, James R
dc.contributor.authorGalligan, James J
dc.date.accessioned2020-03-25T16:33:46Z
dc.date.available2020-03-25T16:33:46Z
dc.date.issued2020-02-20
dc.identifier.citationGaffney, D. O., Jennings, E. Q., Anderson, C. C., Marentette, J. O., Shi, T., Oxvig, A. M. S., ... & Roede, J. R. (2020). Non-enzymatic lysine lactoylation of glycolytic enzymes. Cell chemical biology, 27(2), 206-213. doi:10.1016/j.chembiol.2019.11.005en_US
dc.identifier.issn2451-9448
dc.identifier.pmid31767537
dc.identifier.doi10.1016/j.chembiol.2019.11.005
dc.identifier.urihttp://hdl.handle.net/10150/638058
dc.description.abstractPost-translational modifications (PTMs) regulate enzyme structure and function to expand the functional proteome. Many of these PTMs are derived from cellular metabolites and serve as feedback and feedforward mechanisms of regulation. We have identified a PTM that is derived from the glycolytic by-product, methylglyoxal. This reactive metabolite is rapidly conjugated to glutathione via glyoxalase 1, generating lactoylglutathione (LGSH). LGSH is hydrolyzed by glyoxalase 2 (GLO2), cycling glutathione and generating D-lactate. We have identified the non-enzymatic acyl transfer of the lactate moiety from LGSH to protein Lys residues, generating a "LactoylLys'' modification on proteins. GLO2 knockout cells have elevated LGSH and a consequent marked increase in LactoylLys. Using an alkyne-tagged methylglyoxal analog, we show that these modifications are enriched on glycolytic enzymes and regulate glycolysis. Collectively, these data suggest a previously unexplored feedback mechanism that may serve to regulate glycolytic flux under hyperglycemic or Warburg-like conditions.en_US
dc.language.isoenen_US
dc.publisherCELL PRESSen_US
dc.rights© 2019 Elsevier Ltd.en_US
dc.subjectGLO2en_US
dc.subjectHAGHen_US
dc.subjectglyoxalaseen_US
dc.subjecthydroxyacylglutathione hydrolaseen_US
dc.subjectlactoyllysineen_US
dc.subjectlactyllysineen_US
dc.subjectmethylglyoxalen_US
dc.subjectpost-translational modificationen_US
dc.titleNon-enzymatic Lysine Lactoylation of Glycolytic Enzymesen_US
dc.typeArticleen_US
dc.contributor.departmentUniv Arizona, Dept Pharmacol & Toxicol, Coll Pharmen_US
dc.identifier.journalCELL CHEMICAL BIOLOGYen_US
dc.description.note12 month embargo; published online: 22 November 2019en_US
dc.description.collectioninformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.en_US
dc.eprint.versionFinal accepted manuscripten_US
dc.source.journaltitleCell chemical biology
dc.source.volume27
dc.source.issue2
dc.source.beginpage206
dc.source.endpage213.e6
dc.source.countryUnited States
dc.source.countryUnited States


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