4DFG

Crystal Structure of Wild-type HIV-1 Protease with Cyclopentyltetrahydro- furanyl Urethanes as P2-ligand, GRL-0249A

4DFG の概要

• エントリーDOI: 10.2210/pdb4dfg/pdb
• 関連するPDBエントリー: 2HB3 2IEN 2Z4O 3DJK 3DK1 3H5B 3I6O 3OK9 3ST5
• 分子名称: Protease, SODIUM ION, CHLORIDE ION, ... (5 entities in total)
• 機能のキーワード: aspartic acid protease, hiv-1 protease inhibitor grl-0249a, cyclopentyltetrahydro- furanyl urethanes p2-ligands, wild-type hiv-1 protease, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Human immunodeficiency virus type 1 (HIV-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: 22302.90

構造登録者

Wang, Y.-F.,Agniswamy, J.,Weber, I.T. (登録日: 2012-01-23, 公開日: 2012-03-21, 最終更新日: 2023-09-13)

主引用文献

Ghosh, A.K.,Chapsal, B.D.,Steffey, M.,Agniswamy, J.,Wang, Y.F.,Amano, M.,Weber, I.T.,Mitsuya, H.
Substituent effects on P2-cyclopentyltetrahydrofuranyl urethanes: Design, synthesis, and X-ray studies of potent HIV-1 protease inhibitors.
Bioorg.Med.Chem.Lett., 22:2308-2311, 2012

PubMed Abstract: The design, synthesis, and biological evaluation of novel C3-substituted cyclopentyltetrahydrofuranyl (Cp-THF)-derived HIV-1 protease inhibitors are described. Various C3-functional groups on the Cp-THF ligand were investigated in order to maximize the ligand-binding site interactions in the flap region of the protease. Inhibitors 3c and 3d have displayed the most potent enzyme inhibitory and antiviral activity. Both inhibitors have maintained impressive activity against a panel of multidrug resistant HIV-1 variants. A high-resolution X-ray crystal structure of 3c-bound HIV-1 protease revealed a number of important molecular insights into the ligand-binding site interactions.

PubMed: 22364812
DOI: 10.1016/j.bmcl.2012.01.061

実験手法

X-RAY DIFFRACTION (1.23 Å)