P53(Y220C) His Tag Protein, Human

P53-Y220C is one of the most representative conformational mutants of the TP53 gene, resulting from a substitution of tyrosine to cysteine at position 220. This mutation is located on the surface of the DNA-binding domain (DBD) and does not directly participate in DNA contact. The Y220C mutation creates a surface crevice or “pocket” within the protein core, severely disrupting the thermodynamic stability of the p53 protein. This causes it to undergo conformational changes and aggregate at physiological temperatures, leading to a loss of DNA-binding ability and transcriptional activation function.

In contrast to many other types of mutations, the unique crevice created by the Y220C mutation provides an excellent “druggable” target for the development of small-molecule “chaperone” drugs. These small molecules can precisely bind to this crevice, acting like “glue” to stabilize the folded conformation of the p53 protein, thereby restoring its tumor suppressor function. Consequently, P53-Y220C has become one of the most intensively studied and advanced mutation targets in the field of p53-targeted therapeutics.