9PO6
Influenza PA-N Endonuclease with compound 4 ((6M)-3-hydroxy-4-oxo-6-(2-phenoxyphenyl)-1,4-dihydropyridine-2-carboxylic acid)
This is a non-PDB format compatible entry.
Summary for 9PO6
| Entry DOI | 10.2210/pdb9po6/pdb |
| Related | 9PMP 9PMR 9PN2 9PN3 9PNL 9PNM |
| Descriptor | Polymerase acidic protein, MANGANESE (II) ION, (6M)-3-hydroxy-4-oxo-6-(2-phenoxyphenyl)-1,4-dihydropyridine-2-carboxylic acid (3 entities in total) |
| Functional Keywords | metal binding protein, endonuclease, influenza endonuclease, lyase |
| Biological source | Influenza A virus (A/California/04/2009(H1N1)) |
| Total number of polymer chains | 1 |
| Total formula weight | 22857.72 |
| Authors | |
| Primary citation | Kohlbrand, A.J.,Stokes, R.W.,Sankaran, B.,Cohen, S.M. Substituent size versus metal binding of inhibitors with variants of influenza endonuclease. J.Inorg.Biochem., 277:113210-113210, 2025 Cited by PubMed Abstract: The influenza virus causes a significant burden of illness each year. Although vaccination is the most effective method to prevent seasonal influenza infection, viral escape mechanisms make vaccine composition difficult to predict. Antivirals are crucial for decreasing rates of morbidity and mortality from influenza viral infection. The newest anti-influenza drugs target the RNA-dependent RNA polymerase acidic N-terminal (PA) endonuclease, a critical component of influenza viral replication machinery. This study examines the structure of inhibitors of PA that utilize a hydroxypyridinone-based metal-binding pharmacophore (MBP). Specifically, this report explores how the size of substituent groups impacts the binding conformation and affinity of a series of compounds against both wild-type (WT) and resistance mutant strains, I38T and E23K. Co-crystal structures revealed that the distance between compounds and enzyme residue 38 was conserved to maintain strong interactions, resulting in deviations from ideal coordination geometries at the active site metal centers. This suggests the interactions with residue 38 with each compound is important and can impact inhibitor potency as a consequence of distortions in the metal binding geometry of the compounds. PubMed: 41512630DOI: 10.1016/j.jinorgbio.2025.113210 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.17 Å) |
Structure validation
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