2X0V
STRUCTURE OF THE P53 CORE DOMAIN MUTANT Y220C BOUND TO 4-(trifluoromethyl)benzene-1,2-diamine
Summary for 2X0V
| Entry DOI | 10.2210/pdb2x0v/pdb |
| Related | 1A1U 1AIE 1C26 1DT7 1GZH 1H26 1HS5 1JSP 1KZY 1MA3 1OLG 1OLH 1PES 1PET 1SAE 1SAF 1SAH 1SAJ 1SAK 1SAL 1TSR 1TUP 1UOL 1XQH 1YCQ 1YCR 1YCS 2AC0 2ADY 2AHI 2ATA 2B3G 2BIM 2BIN 2BIO 2BIP 2BIQ 2FEJ 2FOJ 2FOO 2GS0 2H1L 2J0Z 2J10 2J11 2J1W 2J1X 2J1Y 2J1Z 2J20 2J21 2VUK 2WGX 2X0U 2X0W 3SAK |
| Descriptor | CELLULAR TUMOR ANTIGEN P53, ZINC ION, 4-(TRIFLUOROMETHYL)BENZENE-1,2-DIAMINE, ... (4 entities in total) |
| Functional Keywords | cell cycle, host-virus interaction, transcription regulation, transcription factor, li-fraumeni drug discovery, surface crevice, tumor suppressor, protein stabilization, transcription, metal binding, cancer, apoptosis |
| Biological source | HOMO SAPIENS (HUMAN) |
| Total number of polymer chains | 2 |
| Total formula weight | 49544.72 |
| Authors | Basse, N.,Kaar, J.L.,Joerger, A.C.,Fersht, A.R. (deposition date: 2009-12-17, release date: 2010-01-26, Last modification date: 2023-12-20) |
| Primary citation | Basse, N.,Kaar, J.L.,Settanni, G.,Joerger, A.C.,Rutherford, T.J.,Fersht, A.R. Toward the Rational Design of P53-Stabilizing Drugs: Probing the Surface of the Oncogenic Y220C Mutant. Chem.Biol., 17:46-, 2010 Cited by PubMed Abstract: The p53 cancer mutation Y220C induces formation of a cavity on the protein's surface that can accommodate stabilizing small molecules. We combined fragment screening and molecular dynamics to assess the druggability of p53-Y220C and map ligand interaction sites within the mutational cavity. Elucidation of the binding mode of fragment hits by crystallography yielded a clear picture of how a drug might dock in the cavity. Simulations that solvate the protein with isopropanol found additional sites that extend the druggable surface. Moreover, structural observations and simulation revealed the dynamic landscape of the cavity, which improves our understanding of the impact of the mutation on p53 stability. This underpins the importance of considering flexibility of the cavity in screening for optimized ligands. Our findings provide a blueprint for the design of effective drugs that rescue p53-Y220C. PubMed: 20142040DOI: 10.1016/J.CHEMBIOL.2009.12.011 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.8 Å) |
Structure validation
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