Investigation of the binding of p53 and DNA upon DNA-contact mutations (R273C and R273H) and their effect on cancer
نویسندگان
چکیده
In this contribution, we elucidate the structural and functional consequence of p53 proteins upon DNA-contact (R273C & R273H) mutations and their molecular mechanisms at the atomic level by molecular dynamics simulations. Further, we also carried out a docking study to observe the p53-DNA binding pattern upon DNA-contact mutations. In this study we clearly observe that, due to DNA-contact mutations, the p53 structure is damaged and the p53-DNA interaction pattern is lost, which may lead to cancer.
منابع مشابه
Structure and Function of p53-DNA Complexes with Inactivation and Rescue Mutations: A Molecular Dynamics Simulation Study.
The tumor suppressor protein p53 can lose its function upon DNA-contact mutations (R273C and R273H) in the core DNA-binding domain. The activity can be restored by second-site suppressor or rescue mutations (R273C_T284R, R273H_T284R, and R273H_S240R). In this paper, we elucidate the structural and functional consequence of p53 proteins upon DNA-contact mutations and rescue mutations and the und...
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A p53 hot-spot mutation found frequently in human cancer is the replacement of R273 by histidine or cysteine residues resulting in p53 loss of function as a tumor suppressor. These mutants can be reactivated by the incorporation of second-site suppressor mutations. Here, we present high-resolution crystal structures of the p53 core domains of the cancer-related proteins, the rescued proteins an...
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