Summary information and primary citation

PDB-id
6bsg; SNAP-derived features in text and JSON formats; DNAproDB
Class
viral protein-DNA-RNA-inhibitor
Method
X-ray (2.44 Å)
Summary
Structure of hiv-1 rt complexed with RNA-DNA hybrid in an RNA hydrolysis-off mode
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.

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