DSSR-PyMOL cartoon-block schematics: PDB entry 6bsi

PDB-id

6bsi; DSSR-derived features in text and JSON formats

Class

viral protein-DNA-RNA-inhibitor

Method

X-ray (3.25 Å)

Summary

Structure of hiv-1 rt complexed with an RNA-DNA hybrid containing the polypurine-tract sequence

Reference

Tian L, Kim MS, Li H, Wang J, Yang W (2018): "Structure of HIV-1 reverse transcriptase cleaving RNA in an RNA/DNA hybrid." Proc. Natl. Acad. Sci. U.S.A., 115, 507-512. doi: 10.1073/pnas.1719746115.

Abstract

HIV-1 reverse transcriptase (RT) contains both DNA polymerase and RNase H activities to convert the viral genomic RNA to dsDNA in infected host cells. Here we report the 2.65-Å resolution structure of HIV-1 RT engaging in cleaving RNA in an RNA/DNA hybrid. A preferred substrate sequence is absolutely required to enable the RNA/DNA hybrid to adopt the distorted conformation needed to interact properly with the RNase H active site in RT. Substituting two nucleotides 4 bp upstream from the cleavage site results in scissile-phosphate displacement by 4 Å. We also have determined the structure of HIV-1 RT complexed with an RNase H-resistant polypurine tract sequence, which adopts a rigid structure and is accommodated outside of the nuclease active site. Based on this newly gained structural information and a virtual drug screen, we have identified an inhibitor specific for the viral RNase H but not for its cellular homologs.