8CTA

Minimal 2:2 Ternary Complex between BI-224436 bound HIV-1 Integrase Catalytic Core Domain Dimer and Carboxy Terminal Domains

8CTA の概要

• エントリーDOI: 10.2210/pdb8cta/pdb
• 分子名称: Integrase, (2S)-tert-butoxy[4-(2,3-dihydropyrano[4,3,2-de]quinolin-7-yl)-2-methylquinolin-3-yl]acetic acid, 1,2-ETHANEDIOL, ... (5 entities in total)
• 機能のキーワード: viral dna integration, dna binding, ledgf binding, viral protein
• 由来する生物種: Human immunodeficiency virus 1; 詳細
• タンパク質・核酸の鎖数: 16
• 化学式量合計: 195681.97

構造登録者

Gupta, K.,Van Duyne, G.D.,Eilers, G.,Bushman, F.D. (登録日: 2022-05-13, 公開日: 2023-02-22, 最終更新日: 2023-10-25)

主引用文献

Eilers, G.,Gupta, K.,Allen, A.,Montermoso, S.,Murali, H.,Sharp, R.,Hwang, Y.,Bushman, F.D.,Van Duyne, G.
Structure of a HIV-1 IN-Allosteric inhibitor complex at 2.93 angstrom resolution: Routes to inhibitor optimization.
Plos Pathog., 19:e1011097-e1011097, 2023

PubMed Abstract: HIV integrase (IN) inserts viral DNA into the host genome and is the target of the strand transfer inhibitors (STIs), a class of small molecules currently in clinical use. Another potent class of antivirals is the allosteric inhibitors of integrase, or ALLINIs. ALLINIs promote IN aggregation by stabilizing an interaction between the catalytic core domain (CCD) and carboxy-terminal domain (CTD) that undermines viral particle formation in late replication. Ongoing challenges with inhibitor potency, toxicity, and viral resistance motivate research to understand their mechanism. Here, we report a 2.93 Å X-ray crystal structure of the minimal ternary complex between CCD, CTD, and the ALLINI BI-224436. This structure reveals an asymmetric ternary complex with a prominent network of π-mediated interactions that suggest specific avenues for future ALLINI development and optimization.

PubMed: 36867659
DOI: 10.1371/journal.ppat.1011097

実験手法

X-RAY DIFFRACTION (2.93 Å)