Open Access Journal

ISSN : 2456-1304 (Online)

International Journal of Engineering Research in Electronics and Communication Engineering(IJERECE)

Monthly Journal for Electronics and Communication Engineering

Open Access Journal

International Journal of Science Engineering and Management (IJSEM)

Monthly Journal for Science Engineering and Management

ISSN : 2456-1304 (Online)

In Silico Analysis of SNPs and Gene Disease Association Analysis, Homology Modelling and Molecular Docking of Human GST Gene using Bioinformatics tools

Author : Krishna Saraiya 1 Kinnari N. Mistry 2

Date of Publication :11th May 2021

Abstract: GST gene codes for metabolic isozymes catalyze the conjugation reaction where glutathione is reduced to xenobiotic substrate and mutation in GST gene can cause cancer. During this study, mutation found in GST and efficacy of current treatment is determined using computational and web-based tools. Diseases related to GST were obtained using DisGeNET. Primarily breast carcinoma and malignant tumor of prostate are selected for further analysis. Using Cystoscape network analysis is obtained. Highest scores were displayed in breast carcinoma and malignant tumor of prostate for GSTZ1 and GSTA1 respectively, which allows predicting role of GST in disorder. Disease specific mutations were collected from ClinVar, DisGeNET and UniProt databases. I-Tasser platform is employed to perform homology modelling and validate by Ramachandran plot. Molecular docking was performed by PyRx of generated model against drugs/ligands commonly used to control the disease. Drugs showed high binding affinity towards generated protein model of GST might be used as potential drug target for the disease.

Reference :

    1. Ali-Osman F, Akande O, Antoun G, Mao JX, and Buo- lamwini J. Molecular cloning, characterization, and expres- sion in Escherichia coli of full-length cDNAs of three human glutathione S-transferase Pi gene variants. Evidence for dif- ferential catalytic activity of the encoded proteins. J Biol Chem 272: 10004–10012, 1997.
    2. Board, P. G. & Menon, D. Glutathione transferases, regulators of cellular metabolism and physiology. Biochim. Biophys. Acta 1830, 3267 –3288 (2013).
    3. Choi, Y. and Chan, A.P. (2015) PROVEAN Web Server: a tool to predict the functional effect of amino acid substitutions and indels. Bioinformatics, 31(16):2745-7. [4] Choi, Y., Sims, G.E., Murphy, S., Miller, J.R. and Chan, A.P. (2012) Predicting the Functional Effect of Amino Acid Substitutions and Indels. PLoS ONE, 7(10):e46688.
    4. Dallakyan, S. and Olson, A.J. (2015) Small-molecule Library Screening by docking with PyRx. Methods Mol Bio, 1263:243-50.
    5. Daniel WB,Vasillis V, “Analysis of the Glutathione S-transferase gene family” Human genomics 2004; 460-464.
    6. Daniel WB,Vasillis V, “Analysis of the Glutathione S-transferase gene family” Human genomics 2004; 460-464.
    7. Darazy M (2011) CYP1A1, CYP2E1, and GSTM1 gene polymorphisms and susceptibility to colorectal and gastrin cancer among Lebanese. Genet Test Mol Biomarkers. 15: 423-429.
    8. Deponte, M. Glutathione catalysis and the reaction mechanisms of glutathione-dependent enzymes. Biochim. Biophys. Acta 1830, 3217–3266 (2013).
    9. Di Pietro, G., Magno, L. A. & Rios-Santos, F. Glutathione S-transferases: an overview in cancer research. Expert. Opin. Drug. Metab. Toxicol. 6, 153 –170 (2010).
    10. Gate, L. & Tew, K. D. Glutathione S-transferases as emerging therapeutic targets. Expert. Opin. Ther. Targets 5, 477 –489 (2001).
    11.  Hayes,J .D.andPulford, D.J.(1995),„The glutathione S -transferasegene family:Regulation ofGST andthe contribution ofthe isoenzymesto cancerchemoprotection anddrugresistance‟, Crit. Rev. Biochem. Mol. Biol. Vol. 30,pp.445–600.

Recent Article