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Science. 2013 Aug 2;341(6145):549-53. doi: 10.1126/science.1238327.

Functional lysine modification by an intrinsically reactive primary glycolytic metabolite.

Author information

1
The Skaggs Institute for Chemical Biology and Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA 92037, USA. rmoeller@scripps.edu

Abstract

The posttranslational modification of proteins and their regulation by metabolites represent conserved mechanisms in biology. At the confluence of these two processes, we report that the primary glycolytic intermediate 1,3-bisphosphoglycerate (1,3-BPG) reacts with select lysine residues in proteins to form 3-phosphoglyceryl-lysine (pgK). This reaction, which does not require enzyme catalysis, but rather exploits the electrophilicity of 1,3-BPG, was found by proteomic profiling to be enriched on diverse classes of proteins and prominently in or around the active sites of glycolytic enzymes. pgK modifications inhibit glycolytic enzymes and, in cells exposed to high glucose, accumulate on these enzymes to create a potential feedback mechanism that contributes to the buildup and redirection of glycolytic intermediates to alternate biosynthetic pathways.

PMID:
23908237
PMCID:
PMC4005992
DOI:
10.1126/science.1238327
[Indexed for MEDLINE]
Free PMC Article

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