ArticleCell metabolism2017
A Class of Reactive Acyl-CoA Species Reveals the Non-enzymatic Origins of Protein Acylation.
Article in Cell metabolism, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 163 papers, 1 of them a synthesis that pooled it.
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Who cites it
163 citing papers in PubMed, 1 synthesis or guideline pooled it, 260 citations in OpenAlex.
- Current computational tools for protein lysine acylation site prediction.Briefings in bioinformatics · 2024Pooled it
- HUNTER catches N-terminal prey of ICP55 in the mitochondria.Nature structural & molecular biology · 2026Article
- Beyond acetylation: Evaluating the emerging biology of lysine acylation.Cell chemical biology · 2026Review
- Substrate Specificity and Kinetic Mechanism of the NAD+-Dependent Deacylase from Mycobacterium tuberculosis, Rv1151c (Mt-Sirt).Biochemistry · 2026Article
- Lactate-induced H3K4me3 histone mark promotes PLOD1-driven prostate cancer invasion.Cell death & disease · 2026Article
- Histone succinylation directly inhibits Jumonji domain demethylases and stabilizes repressive chromatin states.bioRxiv : the preprint server for biology · 2026Article
- Comprehensive Chemoproteomics Unveils Selective HMG-CoA Synthase 1 Inhibitors for Targeting Mevalonate Metabolism in Cancer.Journal of the American Chemical Society · 2026Article
- Review
- A liquid chromatography-mass spectrometry method to quantify total Coenzyme A concentration and isotopic labeling.bioRxiv : the preprint server for biology · 2026Article
- Leucine catabolic enzyme AUH regulates BAT thermogenesis via PPARγ HMGylation and RNA-binding function in male mice.Nature communications · 2026Article
- Aminoadipate-semialdehyde synthase, a potential target for substrate reduction therapy in glutaric aciduria type 1.Scientific reports · 2026Article
- CLOCK-catalyzed histone H3K37 glutarylation suppresses H3K36 trimethylation pathways in glioblastoma.Science advances · 2026Article
- NAD+ and Sirt5 restore mitochondrial bioenergetics failure and improve locomotor defects caused by sucla2 mutations.JCI insight · 2026Article
- Regulation of apoptosis, ferroptosis, and pyroptosis mediated by acetylation.Cell death discovery · 2026Review
- Review
- The function and mechanism of protein acylation in the regulation of viral infection.Virulence · 2025Review
- Covalent Docking to the Active Sites of Thiamine Diphosphate-Dependent Enzymes.Molecules (Basel, Switzerland) · 2025Article
- Odd-Chain Dicarboxylic Acid Feeding Produces a Glutaric Aciduria Type 1-Like Metabolic Signature in Mice.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Cysteine S-acetylation is a widespread post-translational modification on metabolic proteins.npj metabolic health and disease · 2025Article
- Small Molecules as Alternate Substrates for 3-Methylglutaconylation.JIMD reports · 2025Article
103 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 6 institutions in 3 countries.
Funding
Abstract
The mechanisms underlying the formation of acyl protein modifications remain poorly understood. By investigating the reactivity of endogenous acyl-CoA metabolites, we found a class of acyl-CoAs that undergo intramolecular catalysis to form reactive intermediates that non-enzymatically modify proteins. Based on this mechanism, we predicted, validated, and characterized a protein modification: 3-hydroxy-3-methylglutaryl(HMG)-lysine. In a model of altered HMG-CoA metabolism, we found evidence of two additional protein modifications: 3-methylglutaconyl(MGc)-lysine and 3-methylglutaryl(MG)-lysine. Using quantitative proteomics, we compared the "acylomes" of two reactive acyl-CoA species, namely HMG-CoA and glutaryl-CoA, which are generated in different pathways. We found proteins that are uniquely modified by each reactive metabolite, as well as common proteins and pathways. We identified the tricarboxylic acid cycle as a pathway commonly regulated by acylation and validated malate dehydrogenase as a key target. These data uncover a fundamental relationship between reactive acyl-CoA species and proteins and define a new regulatory paradigm in metabolism.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.