title: Chemical reporter for visualizing metabolic cross-talk between carbohydrate metabolism and protein modification.
abstract: Metabolic chemical reporters have been largely used to study posttranslational modifications. Generally, it was assumed that these reporters entered one biosynthetic pathway, resulting in labeling of one type of modification. However, because they are metabolized by cells before their addition onto proteins, metabolic chemical reporters potentially provide a unique opportunity to read-out on both modifications of interest and cellular metabolism. We report here the development of a metabolic chemical reporter 1-deoxy-N-pentynyl glucosamine (1-deoxy-GlcNAlk). This small-molecule cannot be incorporated into glycans; however, treatment of mammalian cells results in labeling of a variety proteins and enables their visualization and identification. Competition of this labeling with sodium acetate and an acetyltransferase inhibitor suggests that 1-deoxy-GlcNAlk can enter the protein acetylation pathway. These results demonstrate that metabolic chemical reporters have the potential to isolate and potentially discover cross-talk between metabolic pathways in living cells.
authors: Department of Chemistry and ‡Department of Molecular and Computational Biology, University of Southern California , Los Angeles, California 90089, United States.
authors: Balyn W
authors: BW
authors: Zaro
authors: Kelly N
authors: KN
authors: Chuh
authors: Matthew R
authors: MR
authors: Pratt
mesh_terms: D000107:Acetylation; D000480:Alkynes / Q000032:analysis / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D050260:Carbohydrate Metabolism; D005456:Fluorescent Dyes / Q000737:chemistry; D005944:Glucosamine / Q000031:analogs & derivatives* / Q000032:analysis / Q000737:chemistry / Q000494:pharmacology; D006031:Glycosylation; D006657:Histones / Q000737:chemistry / Q000378:metabolism; D008239:Lysine / Q000378:metabolism; D053858:Metabolic Networks and Pathways; D051379:Mice; D008967:Molecular Biology / Q000379:methods; D015336:Molecular Probe Techniques; D015335:Molecular Probes / Q000737:chemistry*; D041681:NIH 3T3 Cells / Q000187:drug effects; D011499:Protein Processing, Post-Translational; D011506:Proteins / Q000032:analysis / Q000737:chemistry / Q000378:metabolism; D019346:Sodium Acetate / Q000737:chemistry; D053719:Tandem Mass Spectrometry / Q000379:methods; D050880:p300-CBP Transcription Factors / Q000378:metabolism; D000099224:p300-CBP-Associated Factor
chemical_list: D000480:Alkynes; D005456:Fluorescent Dyes; D005944:Glucosamine; D006657:Histones; D008239:Lysine; D015335:Molecular Probes; D011506:Proteins; D019346:Sodium Acetate; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C000601706:1-deoxy-N-pentynyl glucosamine