ArticleA Class of Reactive Acyl-CoA Species Reveals the Non-enzymatic Origins of Protein Acylation

Add time:09/07/2019    Source:sciencedirect.com

SummaryThe 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.

We also recommend Trading Suppliers and Manufacturers of (C5:1) COENZYME A LITHIUM SALT (cas 108347-83-7). Pls Click Website Link as below: cas 108347-83-7 suppliers

Prev:Mechanistic aspects of biological redox reactions involving NADH 1: Ab initio quantum chemical structures of the 1-methyl-nicotinamide and 1-methyl-dihydronicotinamide coenzyme analogues
Next:Research ArticleBarley lipid-transfer protein complexed with palmitoyl CoA: the structure reveals a hydrophobic binding site that can expand to fit both large and small lipid-like ligands)