In Silico Analysis of the Protein Structure of Tumor Suppressor Genes in Humans

Authors : Kooffreh M.E, Okon E.A., Ekerete E.E. and Simon I.

Volume/Issue : Volume 4 - 2019, Issue 2 - February

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Tumor suppressor genes encode for proteins that are involved in inhibition of cell proliferation, induction of apoptosis, DNA damage repair and inhibition of metastasis and these are crucial to normal cell development and differentiation. The study examined the secondary protein structure, tertiary protein structure, the G≡C content of Rb, p53, BRCA1 and BRCA2 human tumor suppressor genes and the phylogenetic relationship between them. The nucleotide and amino acid sequences of the genes were obtained from the GenBank, secondary protein structure of the proteins were determined using Gor4 online software, while the tertiary protein structure was determined using phyre2 online software. Phylogenetic relationship was computed using MEGA 6 software and G≡C content was measured using GENSCAN software. Secondary structure of the genes contained Alpha helix, extended strand and random coiling; with BRCA1 having the highest percentage (46.15%) for Alpha helices and lowest (18.07%) in p53 gene; the percentage for extended strand was highest (19.23%) in BRCA1 and lowest (11.31%) in Rb gene; and random coil percentage was highest (52.59%) in p53 and lowest (31.34%) in BRCA2. The phylogenetic tree showed evolutionary relationship between the genes with BRCA1 gene being the common ancestor of all sampled genes and BRCA2 and Rb arising from the same cluster, the tertiary structure was then determined for each representative of the three (3) clusters resulting from the phylogenetic tree construction. The G≡C content obtained in percentage were 52.59, 50.07, 36.02 and 31.34 in p53, BRAC1, Rb and BRAC2 respectively. These findings may become useful in trying to understand how tumor suppressor genes function and also assist in emerging anti-cancer strategies.

Keywords : Tumor Suppressor Genes. Phylogenetic Tree, G≡C Content, Protein Structure.


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