4ZHR

Structure of HIV-1 RT Q151M mutant

4ZHR の概要

• エントリーDOI: 10.2210/pdb4zhr/pdb
• 分子名称: RT p66 subunit, RT p51 subunit (3 entities in total)
• 機能のキーワード: hiv-1 reverse transcriptase, closed conformation, q151m, transferase
• 由来する生物種: Human immunodeficiency virus 1 (HIV-1); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 115941.37

構造登録者

Nakamura, A.,Tamura, N.,Yasutake, Y. (登録日: 2015-04-27, 公開日: 2015-11-11, 最終更新日: 2023-11-08)

主引用文献

Nakamura, A.,Tamura, N.,Yasutake, Y.
Structure of the HIV-1 reverse transcriptase Q151M mutant: insights into the inhibitor resistance of HIV-1 reverse transcriptase and the structure of the nucleotide-binding pocket of Hepatitis B virus polymerase.
Acta Crystallogr.,Sect.F, 71:1384-1390, 2015

PubMed Abstract: Hepatitis B virus polymerase (HBV Pol) is an important target for anti-HBV drug development; however, its low solubility and stability in vitro has hindered detailed structural studies. Certain nucleotide reverse transcriptase (RT) inhibitors (NRTIs) such as tenofovir and lamivudine can inhibit both HBV Pol and Human immunodeficiency virus 1 (HIV-1) RT, leading to speculation on structural and mechanistic analogies between the deoxynucleotide triphosphate (dNTP)-binding sites of these enzymes. The Q151M mutation in HIV-1 RT, located at the dNTP-binding site, confers resistance to various NRTIs, while maintaining sensitivity to tenofovir and lamivudine. The residue corresponding to Gln151 is strictly conserved as a methionine in HBV Pol. Therefore, the structure of the dNTP-binding pocket of the HIV-1 RT Q151M mutant may reflect that of HBV Pol. Here, the crystal structure of HIV-1 RT Q151M, determined at 2.6 Å resolution, in a new crystal form with space group P321 is presented. Although the structure of HIV-1 RT Q151M superimposes well onto that of HIV-1 RT in a closed conformation, a slight movement of the β-strands (β2-β3) that partially create the dNTP-binding pocket was observed. This movement might be caused by the introduction of the bulky thioether group of Met151. The structure also highlighted the possibility that the hydrogen-bonding network among amino acids and NRTIs is rearranged by the Q151M mutation, leading to a difference in the affinity of NRTIs for HIV-1 RT and HBV Pol.

PubMed: 26527265
DOI: 10.1107/S2053230X15017896

実験手法

X-RAY DIFFRACTION (2.601 Å)