Tumor protein p53 Tyr220Cys mutant (TP53 Y220C) (TP53 Y220C)

TP53 Y220C refers to the tumor protein p53 with a tyrosine-to-cysteine substitution at position 220, a recurrent hotspot mutation in cancers including AML and MDS. This structural mutation creates a unique hydrophobic surface crevice or pocket in the DNA-binding domain, reducing thermal stability (melting at physiological temperatures), impairing DNA binding, promoting denaturation and aggregation, and abrogating wild-type p53 tumor suppressor functions. Small molecules like PC14586 bind this pocket to refold the protein into wild-type-like conformation, reactivate transcriptional targets (e.g., MDM2, p21), and induce signaling, though full apoptotic efficacy requires combinations targeting MDM2, XPO1, or BCL-2 due to mechanistic limitations. The query specifies a "TP53 Y220C/HLA complex," but no search results describe such a complex; available data focus solely on the isolated mutant p53 protein or its small-molecule-bound structures (e.g., PDB 6GGC), indicating the complex may be non-standard, hypothetical, or undocumented here.

Other names

p53 Y220Cp53 cancer mutant Y220Cmutant p53-Y220C

Binds hydrophobic pocket created by Y220C mutation to stabilize wild-type conformation, Restore p53 transcriptional activity, Increase thermal stability, Decrease aggregation, Reactivate p53 signaling