Study of pH influence on the stability of 175th codon of P53 genes by computational and modeling methods

Subject Areas : Journal of Physical & Theoretical Chemistry

Nastaran  Asghari Moghaddam ¹ (-)

Received: 2014-12-05 Accepted : 2014-12-05 Published : 2014-12-01

Keywords: P53 gene, Protonation, Mutagenesis,

Abstract :

P53 tumor suppressor gene, also known as “genome guardian” is mutated in more than half of allkind of cancers. In this study we have investigated the controls of environmental pH for P53 genemutation in point of specific sequence which is prone to mutagenesis. The most probable cancerousmutations occur as point mutations in exons 5-8 of P53 gene. The 175th codon of P53 is the thirdmost mutated codon in this gene. By experimental research, it is revealed that acidic pH raised therate of cancer and mutation in 175 CGC codon of P53 gene. It to some extent is due to protonation ofthis three nucleotide codon. Mutation in this codon changes the encoding amino acid andsubsequently produces a protein which has oncogenic features instead of tumor suppressorcharacteristics of original p53 protein. In current study, we perform investigation on the impact ofprotonation on stability of codon 175CGC in this gene. We used HyperChem software for answeringto our mentioned goal above. Our results suggested a reliable answer about the effect of protonationon mentioned codon and its stability. From theoretical point of view, acidity can decrease theinstability of this specific codon. Along with the experimental investigations, our results can to someextent elaborate acidic pH competency to cause mutation.