6BSJ

Structure of HIV-1 RT complexed with an RNA/DNA hybrid sequence non-preferred for RNA hydrolysis

6BSJ の概要

• エントリーDOI: 10.2210/pdb6bsj/pdb
• 分子名称: REVERSE TRANSCRIPTASE P66 SUBUNIT, REVERSE TRANSCRIPTASE P51 SUBUNIT, DNA (5'-D(*GP*TP*AP*TP*GP*CP*CP*TP*AP*TP*AP*GP*TP*TP*AP*TP*TP*GP*TP*GP*GP*CP*C)-3'), ... (9 entities in total)
• 機能のキーワード: hiv-rt, dna-rna complex, rnase h, viral protein, viral protein-dna-rna complex, viral protein-dna-rna-inhibitor complex, viral protein/dna/rna/inhibitor
• 由来する生物種: Human immunodeficiency virus 1; 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 131379.13

構造登録者

Tian, L.,Kim, M.,Yang, W. (登録日: 2017-12-03, 公開日: 2018-01-03, 最終更新日: 2024-05-22)

主引用文献

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

PubMed 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.

PubMed: 29295939
DOI: 10.1073/pnas.1719746115

実験手法

X-RAY DIFFRACTION (2.89 Å)