A graph theoretical approach to the effect of mutation on the flexibility of the DNA binding domain of p53 protein

Rauf, Shah Md. Abdur, Ismael, Mohamed, Sahu, Kamlesh Kumar, Suzuki, Ai, Sahnoun, Riadh, Koyama, Michihisa, Tsuboi, Hideyuki, Hatakeyama, Nozomu, Endou, Akira, Takaba, Hiromitsu, Del Carpio, Carlos A., Kubo, Momoji and Miyamoto, Akira A graph theoretical approach to the effect of mutation on the flexibility of the DNA binding domain of p53 protein Chemical Papers, Vol.63, No. 6, 2009, 654-661

Document type: ńĆl√°nok z ńćasopisu / Journal Article
Collection: Chemical papers  

Author(s) Rauf, Shah Md. Abdur
Ismael, Mohamed
Sahu, Kamlesh Kumar
Suzuki, Ai
Sahnoun, Riadh
Koyama, Michihisa
Tsuboi, Hideyuki
Hatakeyama, Nozomu
Endou, Akira
Takaba, Hiromitsu
Del Carpio, Carlos A.
Kubo, Momoji
Miyamoto, Akira
Title A graph theoretical approach to the effect of mutation on the flexibility of the DNA binding domain of p53 protein
Journal name Chemical Papers
Publication date 2009
Year available 2009
Volume number 63
Issue number 6
ISSN 0366-6352
Start page 654
End page 661
Place of publication Poland
Publisher Versita
Collection year 2009
Language english
Subject 270000 Biological Sciences
270100 Biochemistry and Cell Biology
Abstract/Summary Tumor suppressor protein p53 becomes inactive due to mutation on its DNA binding core domain leading to misbehavior of this protein and preventing its interaction with DNA. In the present study, changes of the protein conformation by five hot spot mutations of T-p53C were assessed preventing the mutants wild-type (WT) behavior. While studies of this nature were undertaken both experimentally and theoretically, the focus is fundamentally on the effects of the mutation on the dynamics of the protein. Hence, the basic concept underlying this study is the change in flexibility or rigidity of the protein. It was found that stable variant T-p53C (PDB-ID: 1uol) that is structurally and functionally very close to wild-type p53 is the most rigid structure and each single carcinogenic mutation on it makes the structure more flexible. We hypothesize that these changes of the molecule’s flexibility disrupt the network of hydrogen bonds associated with the interaction of WT not only at interaction but in the internal structures of the mutants as well, which prevents them from interacting in the WT fashion loosing the anti-cancer properties of WT.
 
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