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Montgomery DC , Garlick JM , Kulkarni RA , Kennedy S , Allali-Hassani A , Kuo YM , Andrews AJ , Wu H , Vedadi M , Meier JL
Global Profiling of Acetyltransferase Feedback Regulation
J Am Chem Soc. 2016 May 25;138(20) :6388-91
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Lysine acetyltransferases (KATs) are key mediators of cell signaling. Methods capable of providing new insights into their regulation thus constitute an important goal. Here we report an optimized platform for profiling KAT-ligand interactions in complex proteomes using inhibitor-functionalized capture resins. This approach greatly expands the scope of KATs, KAT complexes, and CoA-dependent enzymes accessible to chemoproteomic methods. This enhanced profiling platform is then applied in the most comprehensive analysis to date of KAT inhibition by the feedback metabolite CoA. Our studies reveal that members of the KAT superfamily possess a spectrum of sensitivity to CoA and highlight NAT10 as a novel KAT that may be susceptible to metabolic feedback inhibition. This platform provides a powerful tool to define the potency and selectivity of reversible stimuli, such as small molecules and metabolites, that regulate KAT-dependent signaling.
Montgomery, David C Garlick, Julie M Kulkarni, Rhushikesh A Kennedy, Steven Allali-Hassani, Abdellah Kuo, Yin-Ming Andrews, Andrew J Wu, Hong Vedadi, Masoud Meier, Jordan L Research Support, N.I.H., Intramural United States J Am Chem Soc. 2016 May 25;138(20):6388-91. doi: 10.1021/jacs.6b03036. Epub 2016 May 17.