7NUK
Crystal structure of SARS CoV2 main protease in complex with EG009 (modelled using PanDDA event map)
Summary for 7NUK
| Entry DOI | 10.2210/pdb7nuk/pdb |
| Descriptor | 3C-like proteinase, DIMETHYL SULFOXIDE, 2-[2-chloranylethanoyl(propyl)amino]-~{N}-(2-methoxyphenyl)ethanamide, ... (4 entities in total) |
| Functional Keywords | protease, complex, viral protein |
| Biological source | Severe acute respiratory syndrome coronavirus 2 (2019-nCoV, SARS-CoV-2) |
| Total number of polymer chains | 2 |
| Total formula weight | 68262.39 |
| Authors | Oerlemans, R.,Eris, D.,Wang, M.,Sharpe, M.,Domling, A.,Groves, M.R. (deposition date: 2021-03-12, release date: 2021-06-16, Last modification date: 2024-01-31) |
| Primary citation | Sutanto, F.,Shaabani, S.,Oerlemans, R.,Eris, D.,Patil, P.,Hadian, M.,Wang, M.,Sharpe, M.E.,Groves, M.R.,Domling, A. Combining High-Throughput Synthesis and High-Throughput Protein Crystallography for Accelerated Hit Identification. Angew.Chem.Int.Ed.Engl., 60:18231-18239, 2021 Cited by PubMed Abstract: Protein crystallography (PX) is widely used to drive advanced stages of drug optimization or to discover medicinal chemistry starting points by fragment soaking. However, recent progress in PX could allow for a more integrated role into early drug discovery. Here, we demonstrate for the first time the interplay of high throughput synthesis and high throughput PX. We describe a practical multicomponent reaction approach to acrylamides and -esters from diverse building blocks suitable for mmol scale synthesis on 96-well format and on a high-throughput nanoscale format in a highly automated fashion. High-throughput PX of our libraries efficiently yielded potent covalent inhibitors of the main protease of the COVID-19 causing agent, SARS-CoV-2. Our results demonstrate, that the marriage of in situ HT synthesis of (covalent) libraires and HT PX has the potential to accelerate hit finding and to provide meaningful strategies for medicinal chemistry projects. PubMed: 34097796DOI: 10.1002/anie.202105584 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.19 Å) |
Structure validation
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