6F6I

CRYSTAL STRUCTURE OF EBOLAVIRUS GLYCOPROTEIN IN COMPLEX WITH PAROXETINE

6F6I の概要

• エントリーDOI: 10.2210/pdb6f6i/pdb
• 関連するPDBエントリー: 6F5U
• 分子名称: Envelope glycoprotein,GP,GP1, Envelope glycoprotein, alpha-D-mannopyranose-(1-6)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (8 entities in total)
• 機能のキーワード: ebola virus, filoviridae, envelope glycoprotein, protein inhibitor complex, ibuprofen, benztropine, bepridil, paroxetine, sertraline, toremifene, viral protein
• 由来する生物種: Ebola virus; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 57726.52

構造登録者

Ren, J.,Zhao, Y.,Fry, E.E.,Stuart, D.I. (登録日: 2017-12-05, 公開日: 2018-01-03, 最終更新日: 2024-11-13)

主引用文献

Ren, J.,Zhao, Y.,Fry, E.E.,Stuart, D.I.
Target Identification and Mode of Action of Four Chemically Divergent Drugs against Ebolavirus Infection.
J. Med. Chem., 61:724-733, 2018

PubMed Abstract: Here, we show that four chemically divergent approved drugs reported to inhibit Ebolavirus infection, benztropine, bepridil, paroxetine and sertraline, directly interact with the Ebolavirus glycoprotein. Binding of these drugs destabilizes the protein, suggesting that this may be the mechanism of inhibition, as reported for the anticancer drug toremifene and the painkiller ibuprofen, which bind in the same large cavity on the glycoprotein. Crystal structures show that the position of binding and the mode of interaction within the pocket vary significantly between these compounds. The binding constants (K) determined by thermal shift assay correlate with the protein-inhibitor interactions as well as with the antiviral activities determined by virus cell entry assays, supporting the hypothesis that these drugs inhibit viral entry by binding the glycoprotein and destabilizing the prefusion conformation. Details of the protein-inhibitor interactions of these complexes and their relation with binding affinity may facilitate the design of more potent inhibitors.

PubMed: 29272110
DOI: 10.1021/acs.jmedchem.7b01249

実験手法

X-RAY DIFFRACTION (2.4 Å)