7GRY
Crystal structure of SARS-CoV-2 main protease in complex with cpd-21
Summary for 7GRY
| Entry DOI | 10.2210/pdb7gry/pdb |
| Group deposition | Fragment-based screening targeting an open form of the SARS-CoV-2 main protease binding pocket (G_1002282) |
| Descriptor | 3C-like proteinase nsp5, DIMETHYL SULFOXIDE, CHLORIDE ION, ... (6 entities in total) |
| Functional Keywords | protease, sars-cov-2, viral protein |
| Biological source | Severe acute respiratory syndrome coronavirus 2 (2019-nCoV, SARS-CoV-2) |
| Total number of polymer chains | 2 |
| Total formula weight | 68692.26 |
| Authors | Huang, C.-Y.,Metz, A.,Sharpe, M.,Sweeney, A. (deposition date: 2023-11-14, release date: 2024-02-14) |
| Primary citation | Huang, C.Y.,Metz, A.,Lange, R.,Artico, N.,Potot, C.,Hazemann, J.,Muller, M.,Dos Santos, M.,Chambovey, A.,Ritz, D.,Eris, D.,Meyer, S.,Bourquin, G.,Sharpe, M.,Mac Sweeney, A. Fragment-based screening targeting an open form of the SARS-CoV-2 main protease binding pocket. Acta Crystallogr D Struct Biol, 80:123-136, 2024 Cited by PubMed Abstract: To identify starting points for therapeutics targeting SARS-CoV-2, the Paul Scherrer Institute and Idorsia decided to collaboratively perform an X-ray crystallographic fragment screen against its main protease. Fragment-based screening was carried out using crystals with a pronounced open conformation of the substrate-binding pocket. Of 631 soaked fragments, a total of 29 hits bound either in the active site (24 hits), a remote binding pocket (three hits) or at crystal-packing interfaces (two hits). Notably, two fragments with a pose that was sterically incompatible with a more occluded crystal form were identified. Two isatin-based electrophilic fragments bound covalently to the catalytic cysteine residue. The structures also revealed a surprisingly strong influence of the crystal form on the binding pose of three published fragments used as positive controls, with implications for fragment screening by crystallography. PubMed: 38289714DOI: 10.1107/S2059798324000329 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.54 Å) |
Structure validation
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