Literature DB >> 28760905

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

Karen A Kirby1,2, Nataliya A Myshakina3,4, Martin T Christen5, Yue-Lei Chen6, Hilary A Schmidt7,8, Andrew D Huber7,9, Zhaoyong Xi5, Seongmi Kim7,9, Rohit K Rao7,2, Skyler T Kramer7,10, Qiongying Yang7,2, Kamalendra Singh7,2, Michael A Parniak3, Zhengqiang Wang6, Rieko Ishima5, Stefan G Sarafianos1,2,10.   

Abstract

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 [IC50] = 2.6 μM) and RNH functions (IC50 = 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.
Copyright © 2017 American Society for Microbiology.

Entities:  

Keywords:  RNase H; human immunodeficiency virus; inhibitor; reverse transcriptase

Mesh：

Substances：

Year:  2017        PMID： 28760905      PMCID： PMC5610509          DOI： 10.1128/AAC.01351-17

Source DB:  PubMed          Journal:  Antimicrob Agents Chemother        ISSN： 0066-4804            Impact factor:   5.191


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