title: The effect of R249S carcinogenic and H168R-R249S suppressor mutations on p53-DNA interaction, a multi scale computational study.
abstract: In this study we have undertaken the theoretical analysis of the effect of R249S carcinogenic and H168R-R249S suppressor mutation at core domain of the tumor suppressor protein p53, on its natural interaction with DNA using a newly developed method. The results show that the carcinogenic mutation R249S affects the flexibility of L3 loop region in p53, inducing the loss of important hydrogen bonds observed at interaction in the wild-type with DNA, on the other hand the suppressor mutation H168R on the R249S assists in maintaining the wild-type like flexibility of the L3 region in p53 and thus recover the interaction terms lost in the carcinogenic mutation alone. The present study sets a new direction in the development of new drugs that may restore the interactions that lost as a consequence of the carcinogenic mutations in p53.
authors.affiliation: Tohoku University, Aoba, Aramaki, Aoba-ku, Sendai, Japan. rauf_94@yahoo.com
authors.forename: Shah Md Abdur
authors.initials: SM
authors.lastname: Rauf
authors.forename: Mohamed
authors.initials: M
authors.lastname: Ismael
authors.forename: Kamlesh Kumar
authors.initials: KK
authors.lastname: Sahu
authors.forename: Ai
authors.initials: A
authors.lastname: Suzuki
authors.forename: Michihisa
authors.initials: M
authors.lastname: Koyama
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Tsuboi
authors.forename: Nozomu
authors.initials: N
authors.lastname: Hatakeyama
authors.forename: Akira
authors.initials: A
authors.lastname: Endou
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Takaba
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Del Carpio
authors.forename: Momoji
authors.initials: M
authors.lastname: Kubo
authors.forename: Akira
authors.initials: A
authors.lastname: Miyamoto
mesh_terms: D001665:Binding Sites; D003198:Computer Simulation; D004247:DNA / Q000737:chemistry* / Q000235:genetics*; D016147:Genes, Tumor Suppressor; D008956:Models, Chemical; D008957:Models, Genetic; D009154:Mutation; D011485:Protein Binding; D025941:Protein Interaction Mapping; D013329:Structure-Activity Relationship; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry* / Q000235:genetics*
chemical_list: C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D004247:DNA