Malami, IbrahimMuhammad, AliyuEtti, Imaobong C.Waziri, Peter M.Alhassan, Alhassan M.2018-03-142018-03-142017-12-081611-2156http://hdl.handle.net/2003/3680110.17877/DE290R-18802R273H mutant p53 is a DNA-contact mutant that renders p53 dysfunctional due to a single substitution of Arg273 for His273. Rescuing R273 mutant p53 implies that a competent molecule would have to bind to the site of DNA-contact hot spots to complement the loss of contact with the DNA-binding domain. Here, curcumin, flavokawain B, and alpinetin were docked against the crystal structure of R273H mutant p53 in silico. Consequently, all the compounds bind to the cavity of R273H mutant p53 with a dissociation constant estimated to have 36.57, 70.77, and 75.11 μM for curcumin, flavokawain B, and alpinetin, respectively. Subsequently, each molecule was able to bind to the R273H mutant p53 by interacting with the DNA-contact hot spot Arg248 and mutant R273H, thereby compensating for the loss of direct contact with the DNA-binding domain. Furthermore, all the molecules were able to induce a direct contact with the consensus site of the DNA binding domain, thus maintaining DNA-contact residues with the DNA. The present findings offer reliminary indirect supporting evidence that small molecular weight compounds may certainly rescue DNA-contact mutant p53, which may lay a foundation for designing a competent and effective molecule capable of rescuing mutant p53 in tumor cells expressing R273H mutant p53.enEXCLI Journal;Vol. 16 2017http://creativecommons.org/licenses/by/4.0/molecular docking simulationR273H mutant p53flavokawain BalpinetincurcuminDNA-binding domain610article (journal)