6PUZ

Structure of HIV cleaved synaptic complex (CSC) intasome bound with magnesium and INSTI XZ446 (compound 4f)

6PUZ の概要

• エントリーDOI: 10.2210/pdb6puz/pdb
• EMDBエントリー: 20485
• 分子名称: Chimeric Sso7d and HIV-1 integrase, viral DNA non-transferred strand, viral DNA transferred strand, ... (7 entities in total)
• 機能のキーワード: integrase, intasome, transposition, viral protein-dna complex, viral protein/dna
• 由来する生物種: Saccharolobus solfataricus (strain ATCC 35092 / DSM 1617 / JCM 11322 / P2); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 185940.25

構造登録者

Lyumkis, D.,Jozwik, I.K.,Passos, D. (登録日: 2019-07-18, 公開日: 2020-02-12, 最終更新日: 2024-03-20)

主引用文献

Passos, D.O.,Li, M.,Jozwik, I.K.,Zhao, X.Z.,Santos-Martins, D.,Yang, R.,Smith, S.J.,Jeon, Y.,Forli, S.,Hughes, S.H.,Burke Jr., T.R.,Craigie, R.,Lyumkis, D.
Structural basis for strand-transfer inhibitor binding to HIV intasomes.
Science, 367:810-814, 2020

PubMed Abstract: The HIV intasome is a large nucleoprotein assembly that mediates the integration of a DNA copy of the viral genome into host chromatin. Intasomes are targeted by the latest generation of antiretroviral drugs, integrase strand-transfer inhibitors (INSTIs). Challenges associated with lentiviral intasome biochemistry have hindered high-resolution structural studies of how INSTIs bind to their native drug target. Here, we present high-resolution cryo-electron microscopy structures of HIV intasomes bound to the latest generation of INSTIs. These structures highlight how small changes in the integrase active site can have notable implications for drug binding and design and provide mechanistic insights into why a leading INSTI retains efficacy against a broad spectrum of drug-resistant variants. The data have implications for expanding effective treatments available for HIV-infected individuals.

PubMed: 32001521
DOI: 10.1126/science.aay8015

実験手法

ELECTRON MICROSCOPY (2.8 Å)