8CTF
The N-terminal domain of PA endonuclease from the influenza H1N1 viral polymerase in complex with 3-hydroxy-4-oxo-1,4-dihydropyridine-2-carboxylic acid
Summary for 8CTF
| Entry DOI | 10.2210/pdb8ctf/pdb |
| Related | 7V04 |
| Descriptor | Polymerase acidic protein, ACETATE ION, 3-hydroxy-4-oxo-1,4-dihydropyridine-2-carboxylic acid, ... (5 entities in total) |
| Functional Keywords | drug discovery, metal-binding pharmacophore, isosteres, influenza endonuclease, viral protein, hydrolase-inhibitor complex, hydrolase/inhibitor |
| Biological source | Influenza A virus |
| Total number of polymer chains | 1 |
| Total formula weight | 22808.69 |
| Authors | Kohlbrand, A.J.,Stokes, R.W.,Karges, J.,Seo, H.,Sankaran, B.,Cohen, S.M. (deposition date: 2022-05-14, release date: 2022-12-21, Last modification date: 2023-10-25) |
| Primary citation | Stokes, R.W.,Kohlbrand, A.J.,Seo, H.,Sankaran, B.,Karges, J.,Cohen, S.M. Carboxylic Acid Isostere Derivatives of Hydroxypyridinones as Core Scaffolds for Influenza Endonuclease Inhibitors. Acs Med.Chem.Lett., 14:75-82, 2023 Cited by PubMed Abstract: Among the most important influenza virus targets is the RNA-dependent RNA polymerase acidic N-terminal (PA) endonuclease, which is a critical component of the viral replication machinery. To inhibit the activity of this metalloenzyme, small-molecule inhibitors employ metal-binding pharmacophores (MBPs) that coordinate to the dinuclear Mn active site. In this study, several metal-binding isosteres (MBIs) were examined where the carboxylic acid moiety of a hydroxypyridinone MBP is replaced with other groups to modulate the physicochemical properties of the compound. MBIs were evaluated for their ability to inhibit PA using a FRET-based enzymatic assay, and their mode of binding in PA was determined using X-ray crystallography. PubMed: 36655124DOI: 10.1021/acsmedchemlett.2c00434 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.14 Å) |
Structure validation
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