A 2-Hydroxyisoquinoline-1,3-Dione Active-Site RNase H Inhibitor Binds in Multiple Modes to HIV-1 Reverse Transcriptase.

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Antimicrobial agents and chemotherapy, ISSN: 1098-6596, Vol: 61, Issue: 10, Page: e01351-17

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Kirby, Karen A; Myshakina, Nataliya A; Christen, Martin T; Chen, Yue-Lei; Schmidt, Hilary A; Huber, Andrew D; Xi, Zhaoyong; Kim, Seongmi; Rao, Rohit K; Kramer, Skyler T; Yang, Qiongying; Singh, Kamalendra; Parniak, Michael A; Wang, Zhengqiang; Ishima, Rieko; Sarafianos, Stefan G Show More Hide
American Society for Microbiology
Pharmacology, Toxicology and Pharmaceutics; Medicine
article description
The RNase H (RNH) function of HIV-1 reverse transcriptase (RT) plays an essential part in the viral life cycle. We report the characterization of YLC2-155, a 2-hydroxyisoquinoline-1,3-dione (HID)-based active-site RNH inhibitor. YLC2-155 inhibits both polymerase (50% inhibitory concentration [IC] = 2.6 μM) and RNH functions (IC = 0.65 μM) of RT but is more effective against RNH. X-ray crystallography, nuclear magnetic resonance (NMR) analysis, and molecular modeling were used to show that YLC2-155 binds at the RNH-active site in multiple conformations.