7H36
Group deposition for crystallographic fragment screening of Coxsackievirus A16 (G-10) 2A protease -- Crystal structure of Coxsackievirus A16 (G-10) 2A protease in complex with Z1688504114 (A71EV2A-x0310)
Summary for 7H36
| Entry DOI | 10.2210/pdb7h36/pdb |
| Group deposition | Group deposition for crystallographic fragment screening of Coxsackievirus A16 (G-10) 2A protease (G_1002288) |
| Descriptor | Protease 2A, 2-cyano-~{N}-(1,3,5-trimethylpyrazol-4-yl)ethanamide, ZINC ION, ... (5 entities in total) |
| Functional Keywords | diamond light source, i03, asap, coxsackievirus a16, crystallographic fragment screening, pandda, pandda2, xchemexplorer, viral protein, hydrolase |
| Biological source | Coxsackievirus A16 More |
| Total number of polymer chains | 1 |
| Total formula weight | 17063.47 |
| Authors | Lithgo, R.M.,Fairhead, M.,Koekemoer, L.,Balcomb, B.H.,Capkin, E.,Chandran, A.V.,Golding, M.,Godoy, A.S.,Aschenbrenner, J.C.,Marples, P.G.,Ni, X.,Thompson, W.,Tomlinson, C.W.E.,Wild, C.,Winokan, M.,Xavier, M.-A.E.,Fearon, D.,von Delft, F. (deposition date: 2024-04-04, release date: 2024-04-24, Last modification date: 2024-10-16) |
| Primary citation | 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 Cited by 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: 38746446DOI: 10.1101/2024.04.29.591684 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.36 Å) |
Structure validation
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