4H4O

Crystal Structure of HIV-1 Reverse Transcriptase (RT) in Complex with (E)-3-(3-(2-(2-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)ethoxy)- 4-fluorophenoxy)-5-fluorophenyl)acrylonitrile (JLJ506), A Non-nucleoside inhibitor

4H4O の概要

• エントリーDOI: 10.2210/pdb4h4o/pdb
• 関連するPDBエントリー: 1S9E 2BE2 2ZD1 4H4M
• 分子名称: Reverse transcriptase/ribonuclease H, Exoribonuclease H, p66 RT, Reverse transcriptase/ribonuclease H, Exoribonuclease H, p51 RT, (2E)-3-(3-{2-[2-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)ethoxy]-4-fluorophenoxy}-5-fluorophenyl)prop-2-enenitrile, ... (4 entities in total)
• 機能のキーワード: polymerase, transferase, hydrolase/inhibitor, rnase, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Human immunodeficiency virus type 1 BH10 (HIV-1); 詳細
• 細胞内の位置: Gag-Pol polyprotein: Host cell membrane; Lipid-anchor. Matrix protein p17: Virion membrane; Lipid- anchor . Capsid protein p24: Virion . Nucleocapsid protein p7: Virion . Reverse transcriptase/ribonuclease H: Virion . Integrase: Virion : P03366 P03366
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 114440.08

構造登録者

Frey, K.M.,Anderson, K.S. (登録日: 2012-09-17, 公開日: 2012-12-05, 最終更新日: 2023-09-20)

主引用文献

Frey, K.M.,Bollini, M.,Mislak, A.C.,Cisneros, J.A.,Gallardo-Macias, R.,Jorgensen, W.L.,Anderson, K.S.
Crystal Structures of HIV-1 Reverse Transcriptase with Picomolar Inhibitors Reveal Key Interactions for Drug Design.
J.Am.Chem.Soc., 134:19501-19503, 2012

PubMed Abstract: X-ray crystal structures at 2.9 Å resolution are reported for two complexes of catechol diethers with HIV-1 reverse transcriptase. The results help elucidate the structural origins of the extreme antiviral activity of the compounds. The possibility of halogen bonding between the inhibitors and Pro95 is addressed. Structural analysis reveals key interactions with conserved residues P95 and W229 of importance for design of inhibitors with high potency and favorable resistance profiles.

PubMed: 23163887
DOI: 10.1021/ja3092642

実験手法

X-RAY DIFFRACTION (2.9 Å)