CAN BE A MOLECULAR MECHANISM FOR IMPAIRED FUNCTION OF THE p53 MUTANTS

SUMMARY Motivation: At present, there are abundant experimental data concerning associations between the mutations in the p53 protein and cancer. Not of all the molecular mechanisms underlying the impairment of p53 function are known. Results: We support here our previous assumption that G245C mutations can give rise to an additional Zn binding site in the immediate vicinity to the functionally significant binding site (Ivanisenko et al., 2005). We demonstrated here that the interaction energy of the Zn ion in the G245C mutant with the de novo arisen site is commensurate with the interaction energy in the wild-type p53. The presence of an additional site in the mutant can damage p53 conformation upon interaction with DNA. Also, using molecular mechanics, we calculated the effects of certain other mutations on the zinc interaction energy with the normal site.