Synthetic Fluorogenic Peptides Reveal Dynamic Substrate Specificity of Depalmitoylases.,Cell Chemical Biology

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Synthetic Fluorogenic Peptides Reveal Dynamic Substrate Specificity of Depalmitoylases.
Cell Chemical Biology ( IF 6.6 ) Pub Date : 2018-11-01 , DOI: 10.1016/j.chembiol.2018.10.005
Neri Amara ₁ , Ian T Foe ₁ , Ouma Onguka ₁ , Megan Garland ₂ , Matthew Bogyo ₂

Affiliation

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.

中文翻译：

合成的荧光肽揭示了去棕榈糖酶的动态底物特异性。

棕榈酰化是翻译后修饰，涉及半胱氨酸残基与16碳饱和脂肪酸的硫酯化反应。关于去棕榈酸酯化的速率或决定这些速率的参数知之甚少。在这里，我们报告了一种模块化的策略，用于合成淬灭的荧光底物，用于特异性检测去棕榈酰酶活性并绘制单个去棕榈糖酶的底物特异性。我们证明人类去棕榈糖脂APT1和APT2，和TgPPT1从寄生虫弓形虫，有不同的特异性，取决于远端的棕榈酰半胱氨酸的氨基酸残基。该信息指导了最佳和非最佳底物以及同工型选择性底物的设计，以检测复杂蛋白质组中特定去棕榈酰化酶的活性。

更新日期：2019-02-07

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