3O9C

Crystal Structure of wild-type HIV-1 Protease in complex with kd20

3O9C の概要

• エントリーDOI: 10.2210/pdb3o9c/pdb
• 関連するPDBエントリー: 3O99 3O9A 3O9B 3O9D 3O9E 3O9F 3O9G 3O9H 3O9I
• 分子名称: Pol polyprotein, (3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yl [(1S,2R)-3-{(1,3-benzodioxol-5-ylsulfonyl)[(2S)-2-methylbutyl]amino}-1-benzyl-2-hydroxypropyl]carbamate (3 entities in total)
• 機能のキーワード: hiv-1 protease, drug resistance, drug design, protease inhibitors, aids, aspartyl protease, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Human immunodeficiency virus 1 (HIV-1)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 22222.27

構造登録者

Schiffer, C.A.,Nalam, M.N.L. (登録日: 2010-08-04, 公開日: 2011-08-10, 最終更新日: 2024-04-03)

主引用文献

Nalam, M.N.,Ali, A.,Reddy, G.S.,Cao, H.,Anjum, S.G.,Altman, M.D.,Yilmaz, N.K.,Tidor, B.,Rana, T.M.,Schiffer, C.A.
Substrate envelope-designed potent HIV-1 protease inhibitors to avoid drug resistance.
Chem.Biol., 20:1116-1124, 2013

PubMed Abstract: The rapid evolution of HIV under selective drug pressure has led to multidrug resistant (MDR) strains that evade standard therapies. We designed highly potent HIV-1 protease inhibitors (PIs) using the substrate envelope model, which confines inhibitors within the consensus volume of natural substrates, providing inhibitors less susceptible to resistance because a mutation affecting such inhibitors will simultaneously affect viral substrate processing. The designed PIs share a common chemical scaffold but utilize various moieties that optimally fill the substrate envelope, as confirmed by crystal structures. The designed PIs retain robust binding to MDR protease variants and display exceptional antiviral potencies against different clades of HIV as well as a panel of 12 drug-resistant viral strains. The substrate envelope model proves to be a powerful strategy to develop potent and robust inhibitors that avoid drug resistance.

PubMed: 24012370
DOI: 10.1016/j.chembiol.2013.07.014

実験手法

X-RAY DIFFRACTION (1.85 Å)