Determinants of Active-Site Inhibitor Interaction with HIV-1 RNase H.

ABSTRACT: The ribonuclease H (RNH) activity of HIV-1 reverse transcriptase (RT) is essential for viral replication and can be a target for drug development. Yet, no RNH inhibitor to date has substantial antiviral activity to allow advancement into clinical development. Herein, we describe our characterization of the detailed binding mechanisms of RNH active-site inhibitors, YLC2-155 and ZW566, that bind to the RNH domain through divalent metal ions, using NMR, molecular docking, and quantum mechanical calculations. In the presence of Mg²⁺, NMR spectra of RNH exhibited split (two) resonances for some residues upon inhibitor binding, suggesting two binding modes, an observation consistent with the docking results. The relative populations of the two binding conformers were independent of in

SUBMITTER: Xi Z 

PROVIDER: S-EPMC6842066 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature