9EEE

Room-temperature X-ray structure of HIV-1 protease in complex with GRL-10624A inhibitor

これはPDB形式変換不可エントリーです。

9EEE の概要

• エントリーDOI: 10.2210/pdb9eee/pdb
• 分子名称: Protease, (3S,3aS,4S,7R,8aS)-3-methylhexahydro-1H,3H-3a,7-epoxycyclohepta[c]furan-4-yl {(2S,3R)-3-hydroxy-4-[(4-methoxybenzene-1-sulfonyl)(2-methylpropyl)amino]-1-phenylbutan-2-yl}carbamate, CHLORIDE ION, ... (4 entities in total)
• 機能のキーワード: hiv-1 protease, homodimer, inhibitor complex, hydrolase-inhibitor complex, 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: 22169.02

構造登録者

Kovalevsky, A.,Gerlits, O.,Ghosh, A. (登録日: 2024-11-19, 公開日: 2025-02-05, 最終更新日: 2025-02-12)

主引用文献

Ghosh, A.K.,Yadav, M.,Sharma, A.,Johnson, M.,Ghosh, A.K.,Prasad, R.,Amano, M.,Gerlits, O.,Kovalevsky, A.,Mitsuya, H.
Potent HIV‐1 protease inhibitors containing oxabicyclo octanol-derived P2-ligands: Design, synthesis, and X‐ray structural studies of inhibitor-HIV-1 protease complexes.
Bioorg.Med.Chem.Lett., 120:130109-130109, 2025

PubMed Abstract: We describe here the design, synthesis, and X-ray structural studies of a new class of HIV-1 protease inhibitors containing 8-oxabicyclo[3.2.1]octanol-derived P2 ligands. We investigated the functional effect of these stereochemically defined fused-poly cyclic ligands on enzyme inhibition and antiviral activity in MT-2 cells. The tricyclic core of 8-oxabicyclo[3.2.1]octan-6-ol is designed to interact with the residues in the S2 subsite of HIV-1 protease. The syntheses of the ligands were carried out using the [5+2]-cycloaddition as the key step. Several inhibitors exhibited potent enzyme inhibitory activity. High resolution room-temperature X-ray structures of inhibitor-bound HIV-1 protease were determined. These structures provided important molecular insights for further design and optimization of inhibitor potency.

PubMed: 39848476
DOI: 10.1016/j.bmcl.2025.130109

実験手法

X-RAY DIFFRACTION (1.7 Å)