2PWC

HIV-1 protease in complex with a amino decorated pyrrolidine-based inhibitor

2PWC の概要

• エントリーDOI: 10.2210/pdb2pwc/pdb
• 関連するPDBエントリー: 1XL2 2PQZ 2PWR
• 分子名称: Gag-Pol polyprotein (Pr160Gag-Pol), CHLORIDE ION, N,N'-(3S,4S)-PYRROLIDINE-3,4-DIYLBIS(4-AMINO-N-BENZYLBENZENESULFONAMIDE), ... (5 entities in total)
• 機能のキーワード: protein-ligand complex, hydrolase
• 由来する生物種: Human immunodeficiency virus 1
• 細胞内の位置: Matrix protein p17: Virion (Potential). Capsid protein p24: Virion (Potential). Nucleocapsid protein p7: Virion (Potential). Reverse transcriptase/ribonuclease H: Virion (Potential). Integrase: Virion (Potential): P03367
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 22397.71

構造登録者

Boettcher, J.,Blum, A.,Heine, A.,Diederich, W.E.,Klebe, G. (登録日: 2007-05-11, 公開日: 2008-04-15, 最終更新日: 2024-03-13)

主引用文献

Blum, A.,Bottcher, J.,Heine, A.,Klebe, G.,Diederich, W.E.
Structure-Guided Design of C2-Symmetric HIV-1 Protease Inhibitors Based on a Pyrrolidine Scaffold.
J.Med.Chem., 51:2078-2087, 2008

PubMed Abstract: Infections with the human immunodeficiency virus, which inevitably lead to the development of AIDS, are still among the most serious global health problems causing more than 2.5 million deaths per year. In the pathophysiological processes of this pandemic, HIV protease has proven to be an invaluable drug target because of its essential role in the virus' replication process. By use of pyrrolidine as core structure, symmetric 3,4-bis-N-alkylsulfonamides were designed and synthesized enantioselectively from D-(-)-tartaric acid as a new class of HIV protease inhibitors. Structure-guided design using the cocrystal structure of an initial lead as starting point resulted in a second series of inhibitors with improved affinity. The binding modes of four representatives were determined by X-ray crystallography to elucidate the underlying factors accounting for the SAR. With this information for further rational design, the combination of suitable side chains resulted in a final inhibitor showing a significantly improved affinity of K(i) = 74 nM.

PubMed: 18348517
DOI: 10.1021/jm701142s

実験手法

X-RAY DIFFRACTION (1.78 Å)