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Zinc Finger DNA Recognition and 17 Amino Acids Residues, a Transcriptor Repressor in WT1: Analysis of Base Specificities by Site Directed Mutagenesis

Journal of Clinical and Laboratory Investigation Updates - Volume 4

Journal of Clinical and Laboratory Investigation Updates

Zinc Finger DNA Recognition and 17 Amino Acids Residues, a Transcriptor Repressor in WT1: Analysis of Base Specificities by Site Directed Mutagenesis - Pages 1-10dA

Rukhshan Khurshid1, Muhammad Mustansar1, Shamim Akram2, M. Zamir Ahamad2 and Atiya Abbasi2

1Department of Biochemistry, Fatima Jinnah Medical College, Lahore, Pakistan and 2Department of Biochemistry, AllamaIqbal Medical College, Lahore, Pakistan

DOI: http://dx.doi.org/10.20941/2310-9556.2016.04.1

Abstract: The Wilms' tumor suppressor gene encodes a zinc finger DNA binding protein (WT1), which functions as a transcriptional regulator and has been shown to be involved in the progression of breast cancer. Mutation in the zinc finger region of WT1, originally identified in Wilms' tumor patient, has been associated with loss of its DNA-binding activity. We have studied the intra-molecular ionic interactions at active site residues, in particular the four Cys(2)-His(2) pairs of WT1. We have also mutated some of the crucial amino acid residues involved in binding of DNA and observed the effect of these mutations on the binding pattern. Of the five WT1 mutants analyzed, significant change was observed in Cys416Ala416 mutant where reduction in the van der Waal’s contact was seen between the amino acids, which may also affect coordination with the Zn ion. Two other mutants His434Asp434 and His434Arg434 also showed a loss of coordination of Zn ion with the mutant residue, Asp434. His434 did not interact directly with A1, which may affect the DNA binding pattern and change the normal functioning of WT1. However no significant change was observed in the Ser415Ala415 mutant.

Keywords: Tumor suppressor protein WT1, 3D structure prediction, mutation, breast cancer.

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