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A salt bridge turns off the foot-pocket in class-II HDACs
Jingwei Zhou1, Zuolong Yang, Fan Zhang
1School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, P. R. China. wurb3@mail.sysu.edu.cn limin65@mail.sysu.edu.cn.
Abstract:
Histone Deacetylases (HDACs) are promising anticancer targets and several selective inhibitors have been created based on the architectural differences of foot-pockets among HDACs. However, the "gate-keeper" of foot-pockets is still controversial. Herein, it is for the first time revealed that a conserved R-E salt bridge plays a critical role in keeping foot-pockets closed in class-II HDACs by computational simulations. This finding is further substantiated by our mutagenesis experiments.
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