2AZ9

HIV-1 Protease NL4-3 1X mutant

2AZ9 の概要

• エントリーDOI: 10.2210/pdb2az9/pdb
• 関連するPDBエントリー: 2AZ8 2AZB 2AZC
• 関連するBIRD辞書のPRD_ID: PRD_000434
• 分子名称: PROTEASE RETROPEPSIN, benzyl [(1S,4S,7S,8R,9R,10S,13S,16S)-7,10-dibenzyl-8,9-dihydroxy-1,16-dimethyl-4,13-bis(1-methylethyl)-2,5,12,15,18-pentaoxo-20-phenyl-19-oxa-3,6,11,14,17-pentaazaicos-1-yl]carbamate (3 entities in total)
• 機能のキーワード: hiv, protease, inhibitor, tl-3, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Human immunodeficiency virus 1
• 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 : P03367
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 11712.86

構造登録者

Heaslet, H.,Kutilek, V.,Morris, G.M.,Lin, Y.-C.,Elder, J.H.,Torbett, B.E.,Stout, C.D. (登録日: 2005-09-09, 公開日: 2006-02-28, 最終更新日: 2023-08-23)

主引用文献

Heaslet, H.,Kutilek, V.,Morris, G.M.,Lin, Y.-C.,Elder, J.H.,Torbett, B.E.,Stout, C.D.
Structural Insights into the Mechanisms of Drug Resistance in HIV-1 Protease NL4-3
J.Mol.Biol., 356:967-981, 2006

PubMed Abstract: The development of resistance to anti-retroviral drugs targeted against HIV is an increasing clinical problem in the treatment of HIV-1-infected individuals. Many patients develop drug-resistant strains of the virus after treatment with inhibitor cocktails (HAART therapy), which include multiple protease inhibitors. Therefore, it is imperative that we understand the mechanisms by which the viral proteins, in particular HIV-1 protease, develop resistance. We have determined the three-dimensional structure of HIV-1 protease NL4-3 in complex with the potent protease inhibitor TL-3 at 2.0 A resolution. We have also obtained the crystal structures of three mutant forms of NL4-3 protease containing one (V82A), three (V82A, M46I, F53L) and six (V82A, M46I, F53L, V77I, L24I, L63P) point mutations in complex with TL-3. The three protease mutants arose sequentially under ex vivo selective pressure in the presence of TL-3, and exhibit fourfold, 11-fold, and 30-fold resistance to TL-3, respectively. This series of protease crystal structures offers insights into the biochemical and structural mechanisms by which the enzyme can overcome inhibition by TL-3 while recovering some of its native catalytic activity.

PubMed: 16403521
DOI: 10.1016/j.jmb.2005.11.094

実験手法

X-RAY DIFFRACTION (2.5 Å)