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Clickable Analogue of Cerulenin as Chemical Probe to Explore Protein Palmitoylation
journal contribution
posted on 2015-01-16, 00:00 authored by Baohui Zheng, Shunying Zhu, Xu WuDynamic 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.
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acid biosynthesisprotein palmitoylationprotein localizationmass spectrometry studiesExplore Protein PalmitoylationDynamic palmitoylationDHHCSuch probeprofile PATstarget proteinschemical toolpalmitoyl acyltransferasesalkyl chain analoguecysteine residuesproduct ceruleninChemical Probepalmitoylating enzymesCeruleninClickable Analogueproduct inhibitorchemical probestably label
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