6IKA

HIV-1 reverse transcriptase with Q151M/G112S/D113A/Y115F/F116Y/F160L/I159L:DNA:entecavir-triphosphate ternary complex

6IKA の概要

• エントリーDOI: 10.2210/pdb6ika/pdb
• 分子名称: HIV-1 RT p66 subunit, HIV-1 RT p51 subunit, DNA/RNA (38-MER), ... (7 entities in total)
• 機能のキーワード: entecavir 5'-triphosphate, hiv-1, hbv, reverse transcriptase, drug resistance, drug sensitivity, entecavir, transferase-dna complex, replication, transferase/dna
• 由来する生物種: Human immunodeficiency virus 1; 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 256594.30

構造登録者

Yasutake, Y.,Hattori, S.I.,Tamura, N.,Maeda, K. (登録日: 2018-10-15, 公開日: 2019-01-30, 最終更新日: 2023-11-22)

主引用文献

Yasutake, Y.,Hattori, S.I.,Tamura, N.,Matsuda, K.,Kohgo, S.,Maeda, K.,Mitsuya, H.
Active-site deformation in the structure of HIV-1 RT with HBV-associated septuple amino acid substitutions rationalizes the differential susceptibility of HIV-1 and HBV against 4'-modified nucleoside RT inhibitors.
Biochem. Biophys. Res. Commun., 509:943-948, 2019

PubMed Abstract: Nucleoside analogue reverse transcriptase (RT) inhibitors (NRTIs) are major antiviral agents against hepatitis B virus (HBV) and human immunodeficiency virus type-1 (HIV-1). However, the notorious insoluble property of HBV RT has prevented atomic-resolution structural studies and rational anti-HBV drug design. Here, we created HIV-1 RT mutants containing HBV-mimicking sextuple or septuple amino acid substitutions at the nucleoside-binding site (N-site) and verified that these mutants retained the RT activity. The most active RT mutant, HIV-1 RT, carrying Q151M/G112S/D113A/Y115F/F116Y/F160L/I159L was successfully crystallized, and its three-dimensional structure was determined in complex with DNA:dGTP/entecavir-triphosphate (ETV-TP), a potent anti-HBV guanosine analogue RT inhibitor, at a resolution of 2.43 Å and 2.60 Å, respectively. The structures reveal significant positional rearrangements of the amino acid side-chains at the N-site, elucidating the mechanism underlying the differential susceptibility of HIV-1 and HBV against recently reported 4'-modified NRTIs.

PubMed: 30648556
DOI: 10.1016/j.bbrc.2019.01.026

実験手法

X-RAY DIFFRACTION (2.598 Å)