Palmitoylation is a post-translational modification involving the thioesterification of cysteine residues with a 16-carbon-saturated fatty acid. Little is known about rates of depalmitoylation or the parameters that dictate these rates. Here we report a modular strategy to synthesize quenched fluorogenic substrates for the specific detection of depalmitoylase activity and for mapping the substrate specificity of individual depalmitoylases. We demonstrate that human depalmitoylases APT1 and APT2, and TgPPT1 from the parasite Toxoplasma gondii, have distinct specificities that depend on amino acid residues distal to the palmitoyl cysteine. This information informs the design of optimal and non-optimal substrates as well as isoform-selective substrates to detect the activity of a specific depalmitoylase in complex proteomes. In addition to providing tools for studying depalmitoylases, our findings identify a previously unrecognized mechanism for regulating steady-state levels of distinct palmitoylation sites by sequence-dependent control of depalmitoylation rates.
Pubmed ID: 30393067 RIS Download
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This monoclonal targets Glyceraldehyde-3-PDH (GAPDH)
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View all literature mentionsMus musculus with name B6.FVB-Tg(MMTV-PyVT)634Mul/LellJ from IMSR.
View all literature mentionsCell line PC-3 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line SK-OV-3 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsThis monoclonal targets Glyceraldehyde-3-PDH (GAPDH)
View all literature mentions