7GPR

PanDDA analysis group deposition -- Crystal Structure of Enterovirus D68 3C Protease in complex with POB0095

7GPR の概要

• エントリーDOI: 10.2210/pdb7gpr/pdb
• Group deposition: PanDDA analysis group deposition (G_1002271)
• 分子名称: Protease 3C, methyl (3R)-3-(4-methylphenyl)pyrrolidine-3-carboxylate, DIMETHYL SULFOXIDE, ... (4 entities in total)
• 機能のキーワード: diamond i04-1 fragment screening, pandda, xchemexplorer, xce, viral protease, 3c, viral protein
• 由来する生物種: Human Enterovirus D68
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 40549.43

構造登録者

Lithgo, R.M.,Fairhead, M.,Koekemoer, L.,Aschenbrenner, J.C.,Balcomb, B.H.,Godoy, A.S.,Marples, P.G.,Ni, X.,Tomlinson, C.W.E.,Thompson, W.,Wild, C.,Fearon, D.,Walsh, M.A.,von Delft, F. (登録日: 2023-08-24, 公開日: 2023-11-29, 最終更新日: 2024-10-16)

主引用文献

Lithgo, R.M.,Tomlinson, C.W.E.,Fairhead, M.,Winokan, M.,Thompson, W.,Wild, C.,Aschenbrenner, J.C.,Balcomb, B.H.,Marples, P.G.,Chandran, A.V.,Golding, M.,Koekemoer, L.,Williams, E.P.,Wang, S.,Ni, X.,MacLean, E.,Giroud, C.,Godoy, A.S.,Xavier, M.A.,Walsh, M.,Fearon, D.,von Delft, F.
Crystallographic Fragment Screen of Coxsackievirus A16 2A Protease identifies new opportunities for the development of broad-spectrum anti-enterovirals.
Biorxiv, 2024

PubMed Abstract: are the causative agents of paediatric hand-foot-and-mouth disease, and a target for pandemic preparedness due to the risk of higher order complications in a large-scale outbreak. The 2A protease of these viruses is responsible for the self-cleavage of the poly protein, allowing for correct folding and assembly of capsid proteins in the final stages of viral replication. These 2A proteases are highly conserved between species, such as . Inhibition of the 2A protease deranges capsid folding and assembly, preventing formation of mature virions in host cells and making the protease a valuable target for antiviral activity. Herein, we describe a crystallographic fragment screening campaign that identified 75 fragments which bind to the 2A protease including 38 unique compounds shown to bind within the active site. These fragments reveal a path for the development of non-peptidomimetic inhibitors of the 2A protease with broad-spectrum anti-enteroviral activity.

PubMed: 38746446
DOI: 10.1101/2024.04.29.591684

実験手法

X-RAY DIFFRACTION (1.65 Å)