%0 Journal Article %A Zheng, Baohui %A Zhu, Shunying %A Wu, Xu %D 2015 %T Clickable Analogue of Cerulenin as Chemical Probe to Explore Protein Palmitoylation %U https://acs.figshare.com/articles/journal_contribution/Clickable_Analogue_of_Cerulenin_as_Chemical_Probe_to_Explore_Protein_Palmitoylation/2214988 %R 10.1021/cb500758s.s001 %2 https://ndownloader.figshare.com/files/3850561 %K acid biosynthesis %K protein palmitoylation %K protein localization %K mass spectrometry studies %K Explore Protein PalmitoylationDynamic palmitoylation %K DHHC %K Such probe %K profile PATs %K target proteins %K chemical tool %K palmitoyl acyltransferases %K alkyl chain analogue %K cysteine residues %K product cerulenin %K Chemical Probe %K palmitoylating enzymes %K Cerulenin %K Clickable Analogue %K product inhibitor %K chemical probe %K stably label %X Dynamic palmitoylation is an important post-translational modification regulating protein localization, trafficking, and signaling activities. The Asp-His-His-Cys (DHHC) domain containing enzymes are evolutionarily conserved palmitoyl acyltransferases (PATs) mediating diverse protein S-palmitoylation. Cerulenin is a natural product inhibitor of fatty acid biosynthesis and protein palmitoylation, through irreversible alkylation of the cysteine residues in the enzymes. Here, we report the synthesis and characterization of a “clickable” and long alkyl chain analogue of cerulenin as a chemical probe to investigate its cellular targets and to label and profile PATs in vitro and in live cells. Our results showed that the probe could stably label the DHHC-family PATs and enable mass spectrometry studies of PATs and other target proteins in the cellular proteome. Such probe provides a new chemical tool to dissect the functions of palmitoylating enzymes in cell signaling and diseases and reveals new cellular targets of the natural product cerulenin. %I ACS Publications