The effect of R249S carcinogenic and H168R-R249S suppressor mutations on p53-DNA interaction, a multi scale computational study

Shah Md Abdur Rauf, Mohamed Ismael, Kamlesh Kumar Sahu, Ai Suzuki, Michihisa Koyama, Hideyuki Tsuboi, Nozomu Hatakeyama, Akira Endou, Hiromitsu Takaba, Carlos A. Del Carpio, Momoji Kubo, Akira Miyamoto

    研究成果: Contribution to journalArticle査読

    5 被引用数 (Scopus)

    抄録

    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.

    本文言語英語
    ページ(範囲)498-508
    ページ数11
    ジャーナルComputers in Biology and Medicine
    40
    5
    DOI
    出版ステータス出版済み - 5 1 2010

    All Science Journal Classification (ASJC) codes

    • コンピュータ サイエンスの応用
    • 健康情報学

    フィンガープリント

    「The effect of R249S carcinogenic and H168R-R249S suppressor mutations on p53-DNA interaction, a multi scale computational study」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

    引用スタイル