9G6T
p53-Y220C Core Domain Covalently Bound to 5-Chloro-6-methylpyrazine-2-carbonitrile Soaked at 5 mM
This is a non-PDB format compatible entry.
Summary for 9G6T
| Entry DOI | 10.2210/pdb9g6t/pdb |
| Related | 9G5H 9G6U |
| Descriptor | Cellular tumor antigen p53, 5-chloranyl-6-methyl-pyrazine-2-carbonitrile, 1,2-ETHANEDIOL, ... (8 entities in total) |
| Functional Keywords | covalent, snar, stabilization, cell cycle |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 2 |
| Total formula weight | 51642.25 |
| Authors | Stahlecker, J.,Klett, T.,Stehle, T.,Boeckler, F.M. (deposition date: 2024-07-19, release date: 2025-06-11, Last modification date: 2025-07-16) |
| Primary citation | Klett, T.,Stahlecker, J.,Schwer, M.,Jaag, S.J.,Masberg, B.,Knappe, C.,Lammerhofer, M.,Stehle, T.,Boeckler, F.M. S N Ar Reactive Pyrazine Derivatives as p53-Y220C Cleft Binders with Diverse Binding Modes. Drug Des Devel Ther, 19:4727-4753, 2025 Cited by PubMed Abstract: The tumor suppressor p53 is most commonly mutated in human cancer. The structural mutant in the β-sandwich of the protein, p53-Y220C, is the ninth most common p53 mutant. The p53-Y220C mutant has a solvent-accessible hydrophobic pocket, leading to thermal destabilization of the protein. Screening of our covalent fragment library (CovLib) revealed the highly reactive pyrazine derivatives SN006 and SN007, which arylate among other cysteines in p53, the mutation-generated Cys220. Herein, comprehensive structure-activity relationship (SAR) studies of these intrinsically reactive CovLib hits were performed, aiming to identify improved stabilizers for p53-Y220C, with a more balanced reactivity profile, diverse binding modes and a better potential for chemical optimization. PubMed: 40599607DOI: 10.2147/DDDT.S513792 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.56 Å) |
Structure validation
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