9B98
Crystal structure of the human PAD2 protein bound to small molecule
This is a non-PDB format compatible entry.
Summary for 9B98
| Entry DOI | 10.2210/pdb9b98/pdb |
| Descriptor | Protein-arginine deiminase type-2, ACETATE ION, CALCIUM ION, ... (5 entities in total) |
| Functional Keywords | complex, hydrolase |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 79793.48 |
| Authors | Byrnes, L.J.,Vajdos, F. (deposition date: 2024-04-01, release date: 2024-10-09, Last modification date: 2024-10-30) |
| Primary citation | Byrnes, L.J.,Choi, W.Y.,Balbo, P.,Banker, M.E.,Chang, J.,Chen, S.,Cheng, X.,Cong, Y.,Culp, J.,Di, H.,Griffor, M.,Hall, J.,Meng, X.,Morgan, B.,Mousseau, J.J.,Nicki, J.,O'Connell, T.,Ramsey, S.,Shaginian, A.,Shanker, S.,Trujillo, J.,Wan, J.,Vincent, F.,Wright, S.W.,Vajdos, F. Discovery, Characterization, and Structure of a Cell Active PAD2 Inhibitor Acting through a Novel Allosteric Mechanism. Acs Chem.Biol., 19:2186-2197, 2024 Cited by PubMed Abstract: Peptidyl arginine deiminases (PADs) are important enzymes in many diseases, especially those involving inflammation and autoimmunity. Despite many years of effort, developing isoform-specific inhibitors has been a challenge. We describe herein the discovery of a potent, noncovalent PAD2 inhibitor, with selectivity over PAD3 and PAD4, from a DNA-encoded library. The biochemical and biophysical characterization of this inhibitor and two noninhibitory binders indicated a novel, Ca competitive mechanism of inhibition. This was confirmed via X-ray crystallographic analysis. Finally, we demonstrate that this inhibitor selectively inhibits PAD2 in a cellular context. PubMed: 39316753DOI: 10.1021/acschembio.4c00397 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.003 Å) |
Structure validation
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