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Final Accepted Manuscript
Author
Gaffney, Dominique OJennings, Erin Q
Anderson, Colin C
Marentette, John O
Shi, Taoda
Schou Oxvig, Anne-Mette
Streeter, Matthew D
Johannsen, Mogens
Spiegel, David A
Chapman, Eli
Roede, James R
Galligan, James J
Affiliation
Univ Arizona, Dept Pharmacol & Toxicol, Coll PharmIssue Date
2020-02-20Keywords
GLO2HAGH
glyoxalase
hydroxyacylglutathione hydrolase
lactoyllysine
lactyllysine
methylglyoxal
post-translational modification
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CELL PRESSCitation
Gaffney, 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.2019.11.005Journal
CELL CHEMICAL BIOLOGYRights
© 2019 Elsevier Ltd.Collection Information
This 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.Abstract
Post-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.Note
12 month embargo; published online: 22 November 2019ISSN
2451-9448PubMed ID
31767537Version
Final accepted manuscriptae974a485f413a2113503eed53cd6c53
10.1016/j.chembiol.2019.11.005
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