5WG9
Crystal structure of the influenza virus PA endonuclease (E119D mutant) in complex with inhibitor 9b (SRI-30101)
Summary for 5WG9
| Entry DOI | 10.2210/pdb5wg9/pdb |
| Related | 5W3I 5W44 5W73 5W7U 5W92 5W9G 5WA6 5WA7 5WAP 5WB3 5WCS 5WCT 5WDC 5WDN 5WDW 5WE7 5WE9 5WEB 5WEF 5WEI 5WF3 5WFM 5WFW 5WFZ |
| Descriptor | Polymerase acidic protein, MANGANESE (II) ION, SULFATE ION, ... (5 entities in total) |
| Functional Keywords | virus, nuclease, transcription, cap-snatching, hydrolase, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor |
| Biological source | Influenza A virus More |
| Total number of polymer chains | 1 |
| Total formula weight | 23947.29 |
| Authors | Kumar, G.,White, S.W. (deposition date: 2017-07-13, release date: 2018-01-03, Last modification date: 2024-03-13) |
| Primary citation | Beylkin, D.,Kumar, G.,Zhou, W.,Park, J.,Jeevan, T.,Lagisetti, C.,Harfoot, R.,Webby, R.J.,White, S.W.,Webb, T.R. Protein-Structure Assisted Optimization of 4,5-Dihydroxypyrimidine-6-Carboxamide Inhibitors of Influenza Virus Endonuclease. Sci Rep, 7:17139-17139, 2017 Cited by PubMed Abstract: Influenza is a serious hazard to human health that causes hundreds of thousands of deaths annually. Though vaccines and current therapeutics can blunt some of the perilous impact of this viral infection, new treatments are needed due to the constantly evolving nature of this virus. Recently, our growing understanding of an essential influenza viral protein, PA, has led to the development of focused libraries of new small molecules that specifically target the active site of the PA influenza endonuclease, which we report here. Our overarching approach has been to proactively develop lead inhibitors that are less likely to rapidly develop clinical resistance by optimizing inhibitors that retain activity against induced resistant mutants. Here, we report details behind the discovery of new potent inhibitors of wild type and resistant mutant endonucleases along with their high-resolution co-crystal structure-activity relationships. These results add to our understanding of nuclease protein targets and potentially serve as starting points for a new therapeutic approach to the treatment of influenza. PubMed: 29215062DOI: 10.1038/s41598-017-17419-6 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.3 Å) |
Structure validation
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