Journal article
Discovering Targets of Non-enzymatic Acylation by Thioester Reactivity Profiling
CELL CHEMICAL BIOLOGY, v 24(2), pp 231-242
16 Feb 2017
PMID: 28163016
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Non-enzymatic protein modification driven by thioester reactivity is thought to play a major role in the establishment of cellular lysine acylation. However, the specific protein targets of this process are largely unknown. Here we report an experimental strategy to investigate non-enzymatic acylation in cells. Specifically, we develop a chemoproteomic method that separates thioester reactivity from enzymatic utilization, allowing selective enrichment of non-enzymatic acylation targets. Applying this method to cancer cell lines identifies numerous candidate targets of nonenzymatic acylation, including several enzymes in lower glycolysis. Functional studies highlight malonyl-CoA as a reactive thioester metabolite that can modify and inhibit glycolytic enzyme activity. Finally, we show that synthetic thioesters can be used as novel reagents to probe non-enzymatic acylation in living cells. Our studies provide new insights into the targets and drivers of non-enzymatic acylation, and demonstrate the utility of reactivity-based methods to experimentally investigate this phenomenon in biology and disease.
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Details
- Title
- Discovering Targets of Non-enzymatic Acylation by Thioester Reactivity Profiling
- Creators
- Rhushikesh A. Kulkarni - National Cancer InstituteAndrew J. Worth - University of PennsylvaniaThomas T. Zengeya - National Cancer InstituteJonathan H. Shrimp - National Cancer InstituteJulie M. Garlick - National Cancer InstituteAllison M. Roberts - National Cancer InstituteDavid C. Montgomery - National Cancer InstituteCarole Sourbier - National Cancer InstituteBenjamin K. Gibbs - National Cancer InstituteClementina Mesaros - University of PennsylvaniaYien Che Tsai - National Cancer InstituteSudipto Das - LeidosKing C. Chan - LeidosMing Zhou - LeidosThorkell Andresson - LeidosAllan M. Weissman - National Cancer InstituteW. Marston Linehan - National Cancer InstituteIan A. Blair - University of PennsylvaniaNathaniel W. Snyder - Drexel UniversityJordan L. Meier - National Cancer Institute
- Publication Details
- CELL CHEMICAL BIOLOGY, v 24(2), pp 231-242
- Publisher
- Elsevier
- Number of pages
- 12
- Grant note
- ZIA BC011488-02 / Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) ZIABC011488 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) Pennsylvania Department of Health CURE K22ES26235; P30ES013508; ZIA BC011488-02 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA T32ES019851 / NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Environmental Health Sciences (NIEHS)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- A.J. Drexel Autism Institute
- Web of Science ID
- WOS:000397424400016
- Scopus ID
- 2-s2.0-85011304711
- Other Identifier
- 991019167991204721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology