Discovery of PHGPx allosteric activators
作者单位：College of Chemistry and Molecular Engineering StateKey Laboratory for Structural Chemistry of Unstable and Stable Species Peking University Center for Quantitative Biology Peking University College of Chemistry and Molecular Engineering State Key Laboratory for Structural Chemistry of Unstable and Stable SpeciesPeking University
会议名称：《中国生物化学与分子生物学会第十一次会员代表大会暨2014年全国学术会议》
会议日期：2014年
学科分类：0710[理学-生物学] 071010[理学-生物化学与分子生物学] 081704[工学-应用化学] 07[理学] 08[工学] 0817[工学-化学工程与技术]
关 键 词：PHGPx allosteric modulation activator
摘 要：Phospholipid hydroperoxide glutathione peroxidases(PHGPx) is capable of reducing oxidativedamaged biomembranes and reactive oxygen species(ROS) in cells. It plays irreplaceablerole in embryonic development, antioxidation, and male fertility. Activating theprotective effect of PHGPx might be used to cure inflammation, cancer, and other ***, activating target protein by allosteric modulation is a novel strategy in drugdesign. Until now, no compound has been reported to activate the enzymatic activity ofPHGPx. Here, we predicted the allosteric site of PHGPx based on a crystal structure withenzymatic activity, and used structure-based virtual screen for PHGPx activators *** the in vitro activity assay, we got 7 compounds which can activate PHGPx. The bestone has AC50 of 58 ± 5 μM, and can increase the enzymatic activity to about two foldcompared to wild type PHGPx. Moreover, it also exhibits PHGPx activity activation in livingcells. The discovery of these activators verified the possibility to design drugs specific tothe allosteric site, especially allosteric activators. Furthermore, these activators provide anew method to inhibit inflammation more effectively and with less side effects.