7b4h | pdb_00007b4h

Structural basis of reactivation of oncogenic p53 mutants by a small molecule: methylene quinuclidinone (MQ). Human wild-type p53DBD bound to DNA and MQ: wt-DNA-MQ (III)

spinqualitylabelsall models 7b4h, resolution 1.39Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7b4h is a 2 chain structure with sequence from Homo sapiens and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.39Å Ligands: ACT, EDO, FMT, QN8, QNN, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed In response to genotoxic stress, the tumor suppressor p53 acts as a transcription factor by regulating the expression of genes critical for cancer prevention. Mutations in the gene encoding p53 are associated with cancer development. PRIMA-1 and eprenetapopt (APR-246/PRIMA-1(MET)) are small molecules that are converted into the biologically active compound, methylene quinuclidinone (MQ), shown to reactivate mutant p53 by binding covalently to cysteine residues. Here, we investigate the structural basis of mutant p53 reactivation by MQ based on a series of high-resolution crystal structures of cancer-related and wild-type p53 core domains bound to MQ in their free state and in complexes with their DNA response elements. Our data demonstrate that MQ binds to several cysteine residues located at the surface of the core domain. The structures reveal a large diversity in MQ interaction modes that stabilize p53 and its complexes with DNA, leading to a common global effect that is pertinent to the restoration of non-functional p53 proteins. Structural basis of reactivation of oncogenic p53 mutants by a small molecule: methylene quinuclidinone (MQ).,Degtjarik O, Golovenko D, Diskin-Posner Y, Abrahmsen L, Rozenberg H, Shakked Z Nat Commun. 2021 Dec 3;12(1):7057. doi: 10.1038/s41467-021-27142-6. PMID:34862374 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also P53 3D structures

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