6VCE

HIV-1 wild type protease with GRL-026-18A, a crown-like tetrahydropyranotetrahydrofuran with a bridged methylene group as a P2 ligand

6VCE の概要

• エントリーDOI: 10.2210/pdb6vce/pdb
• 関連するPDBエントリー: 2IEN 5TYS 6BZ2
• 分子名称: Protease, SODIUM ION, CHLORIDE ION, ... (6 entities in total)
• 機能のキーワード: aspartic acid protease, hiv-1 protease, cyclic ethers, urethane, carboxamide, inhibitors, multidrug-resistant, synthesis, x-ray crystal structure, backbone binding, viral protein, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 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: 22606.10

構造登録者

Wang, Y.-F.,Kneller, D.W.,Weber, I.T. (登録日: 2019-12-20, 公開日: 2020-07-01, 最終更新日: 2023-10-11)

主引用文献

Ghosh, A.K.,Grillo, A.,Raghavaiah, J.,Kovela, S.,Johnson, M.E.,Kneller, D.W.,Wang, Y.F.,Hattori, S.I.,Higashi-Kuwata, N.,Weber, I.T.,Mitsuya, H.
Design, Synthesis, and X-ray Studies of Potent HIV-1 Protease Inhibitors with P2-Carboxamide Functionalities.
Acs Med.Chem.Lett., 11:1965-1972, 2020

PubMed Abstract: The design, synthesis, biological evaluation, and X-ray structural studies are reported for a series of highly potent HIV-1 protease inhibitors. The inhibitors incorporated stereochemically defined amide-based bicyclic and tricyclic ether derivatives as the P2 ligands with ()-hydroxyethylaminesulfonamide transition-state isosteres. A number of inhibitors showed excellent HIV-1 protease inhibitory and antiviral activity; however, ligand combination is critical for potency. Inhibitor with a difluorophenylmethyl as the P1 ligand, crown-THF-derived acetamide as the P2 ligand, and a cyclopropylaminobenzothiazole P2'-ligand displayed very potent antiviral activity and maintained excellent antiviral activity against selected multidrug-resistant HIV-1 variants. A high resolution X-ray structure of inhibitor -bound HIV-1 protease provided molecular insight into the binding properties of the new inhibitor.

PubMed: 33062180
DOI: 10.1021/acsmedchemlett.9b00670

実験手法

X-RAY DIFFRACTION (1.18 Å)