4ZIP

HIV-1 wild Type protease with GRL-0648A (a isophthalamide-derived P2-Ligand)

4ZIP の概要

• エントリーDOI: 10.2210/pdb4zip/pdb
• 関連するPDBエントリー: 2IEN 3OK9 3QAA 4U8W
• 分子名称: Protease, SODIUM ION, CHLORIDE ION, ... (6 entities in total)
• 機能のキーワード: hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Human immunodeficiency virus type 1 (HIV-1)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 22439.63

構造登録者

Wang, Y.-F.,Agniswamy, J.,Weber, I.T. (登録日: 2015-04-28, 公開日: 2015-07-15, 最終更新日: 2023-09-27)

主引用文献

Ghosh, A.K.,Takayama, J.,Kassekert, L.A.,Ella-Menye, J.R.,Yashchuk, S.,Agniswamy, J.,Wang, Y.F.,Aoki, M.,Amano, M.,Weber, I.T.,Mitsuya, H.
Structure-based design, synthesis, X-ray studies, and biological evaluation of novel HIV-1 protease inhibitors containing isophthalamide-derived P2-ligands.
Bioorg.Med.Chem.Lett., 25:4903-4909, 2015

PubMed Abstract: We describe the design, synthesis and biological evaluation of a series of novel HIV-1 protease inhibitors bearing isophthalamide derivatives as the P2-P3 ligands. We have investigated a range of acyclic and heterocyclic amides as the extended P2-P3 ligands. These inhibitors displayed good to excellent HIV-1 protease inhibitory activity. Also, a number of inhibitors showed very good antiviral activity in MT cells. Compound 5n has shown an enzyme Ki of 0.17 nM and antiviral IC50 of 14 nM. An X-ray crystal structure of inhibitor 5o-bound to HIV-1 protease was determined at 1.11Å resolution. This structure revealed important molecular insight into the inhibitor-HIV-1 protease interactions in the active site.

PubMed: 26096678
DOI: 10.1016/j.bmcl.2015.05.052

実験手法

X-RAY DIFFRACTION (1.11 Å)