2Q55

Crystal structure of KK44 bound to HIV-1 protease

2Q55 の概要

• エントリーDOI: 10.2210/pdb2q55/pdb
• 関連するPDBエントリー: 2q54
• 分子名称: Protease, PHOSPHATE ION, (5S)-N-[(1S,2S,4S)-1-BENZYL-2-HYDROXY-4-{[(2S)-3-METHYL-2-(2-OXOTETRAHYDROPYRIMIDIN-1(2H)-YL)BUTANOYL]AMINO}-5-PHENYLPENTYL]-2-OXO-3-PHENYL-1,3-OXAZOLIDINE-5-CARBOXAMIDE, ... (4 entities in total)
• 機能のキーワード: drug design, hiv-1 protease, protease inhibitor, hydrolase
• 由来する生物種: Human immunodeficiency virus 1
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 22477.31

構造登録者

Schiffer, C.A.,Nalam, M.N.L. (登録日: 2007-05-31, 公開日: 2007-09-04, 最終更新日: 2024-03-13)

主引用文献

Reddy, G.S.,Ali, A.,Nalam, M.N.,Anjum, S.G.,Cao, H.,Nathans, R.S.,Schiffer, C.A.,Rana, T.M.
Design and Synthesis of HIV-1 Protease Inhibitors Incorporating Oxazolidinones as P2/P2' Ligands in Pseudosymmetric Dipeptide Isosteres.
J.Med.Chem., 50:4316-4328, 2007

PubMed Abstract: A series of novel HIV-1 protease inhibitors based on two pseudosymmetric dipeptide isosteres have been synthesized and evaluated. The inhibitors were designed by incorporating N-phenyloxazolidinone-5-carboxamides into the hydroxyethylene and (hydroxyethyl)hydrazine dipeptide isosteres as P2 and P2' ligands. Compounds with (S)-phenyloxazolidinones attached at a position proximal to the central hydroxyl group showed low nM inhibitory activities against wild-type HIV-1 protease. Selected compounds were further evaluated for their inhibitory activities against a panel of multidrug-resistant protease variants and for their antiviral potencies in MT-4 cells. The crystal structures of lopinavir (LPV) and two new inhibitors containing phenyloxazolidinone-based ligands in complex with wild-type HIV-1 protease have been determined. A comparison of the inhibitor-protease structures with the LPV-protease structure provides valuable insight into the binding mode of the new inhibitors to the protease enzyme. Based on the crystal structures and knowledge of structure-activity relationships, new inhibitors can be designed with enhanced enzyme inhibitory and antiviral potencies.

PubMed: 17696512
DOI: 10.1021/jm070284z

実験手法

X-RAY DIFFRACTION (1.9 Å)