E-ISSN 2063-5346
 

Research Article 


EFFECT OF 2677>T/A NON-SYNONYMOUS SINGLE POLYMORPHISM OF HUMAN MDR1 GENE ON SUBSTRATE BINDING TO PERMEABILITY GLYCOPROTEIN

Goutham Yerrakula, Syed Sadathulla T, Kishor GS, Senthil V, Samuel Gideon George P.

Abstract
Background: Non -Synonymous polymorphism in the human MDR1 gene tend to decrease the transporter activity of the P-glycoprotein,a major efflux transporter of endogenous substrates and xenobiotics predominantly cytotoxic agents.Hence this study was determined to assess the effect of 2677 G>T genetic polymorphism of human MDR1 gene on the structure of P-glycoprotein. Methodology: Three dimensional structures of MDR variants were ab-initio model using iTASSER server and drug binding residues of transmembrane domain were predicted using Prankweb server. Substrate binding was analyzed by molecular docking using Autodock 4.2.6.Moreover, statistically significant difference was observed between the binding affinities of substrates to wild and mutant variants (One way Analysis of Variance, df=1, 95% CI). Results & Discussion: Here in, we have investigated the effect of 2677G>T/A non-synonymous polymorphism on substrate transport via human P-glycoprotein through in silico methods. Few molecular modelling studies of human P-gp have stressed the significance of Ser222, Phe303 and Phe343 in substrate conductance. Conclusion: The binding energy of P-gp substrates to the mutant (Ala893Ser and Ala893Pro) was found to be less than that of the wild type. Hence genetic testing of hMDR1need to be done before initiating therapy with cytotoxic and narrow therapeutic P-gp substrates.

Key words: MDR1, Pharmacogenomics, P-glycoprotein, Polymorphism


 
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Pubmed Style

Goutham Yerrakula, Syed Sadathulla T, Kishor GS, Senthil V, Samuel Gideon George P. EFFECT OF 2677>T/A NON-SYNONYMOUS SINGLE POLYMORPHISM OF HUMAN MDR1 GENE ON SUBSTRATE BINDING TO PERMEABILITY GLYCOPROTEIN. ECB. 2022; 11(4): 22-30. doi:10.31838/ecb/2022.11.04.004


Web Style

Goutham Yerrakula, Syed Sadathulla T, Kishor GS, Senthil V, Samuel Gideon George P. EFFECT OF 2677>T/A NON-SYNONYMOUS SINGLE POLYMORPHISM OF HUMAN MDR1 GENE ON SUBSTRATE BINDING TO PERMEABILITY GLYCOPROTEIN. https://www.eurchembull.com/?mno=65762 [Access: September 25, 2022]. doi:10.31838/ecb/2022.11.04.004


AMA (American Medical Association) Style

Goutham Yerrakula, Syed Sadathulla T, Kishor GS, Senthil V, Samuel Gideon George P. EFFECT OF 2677>T/A NON-SYNONYMOUS SINGLE POLYMORPHISM OF HUMAN MDR1 GENE ON SUBSTRATE BINDING TO PERMEABILITY GLYCOPROTEIN. ECB. 2022; 11(4): 22-30. doi:10.31838/ecb/2022.11.04.004



Vancouver/ICMJE Style

Goutham Yerrakula, Syed Sadathulla T, Kishor GS, Senthil V, Samuel Gideon George P. EFFECT OF 2677>T/A NON-SYNONYMOUS SINGLE POLYMORPHISM OF HUMAN MDR1 GENE ON SUBSTRATE BINDING TO PERMEABILITY GLYCOPROTEIN. ECB. (2022), [cited September 25, 2022]; 11(4): 22-30. doi:10.31838/ecb/2022.11.04.004



Harvard Style

Goutham Yerrakula, Syed Sadathulla T, Kishor GS, Senthil V, Samuel Gideon George P (2022) EFFECT OF 2677>T/A NON-SYNONYMOUS SINGLE POLYMORPHISM OF HUMAN MDR1 GENE ON SUBSTRATE BINDING TO PERMEABILITY GLYCOPROTEIN. ECB, 11 (4), 22-30. doi:10.31838/ecb/2022.11.04.004



Turabian Style

Goutham Yerrakula, Syed Sadathulla T, Kishor GS, Senthil V, Samuel Gideon George P. 2022. EFFECT OF 2677>T/A NON-SYNONYMOUS SINGLE POLYMORPHISM OF HUMAN MDR1 GENE ON SUBSTRATE BINDING TO PERMEABILITY GLYCOPROTEIN. European Chemical Bulletin, 11 (4), 22-30. doi:10.31838/ecb/2022.11.04.004



Chicago Style

Goutham Yerrakula, Syed Sadathulla T, Kishor GS, Senthil V, Samuel Gideon George P. "EFFECT OF 2677>T/A NON-SYNONYMOUS SINGLE POLYMORPHISM OF HUMAN MDR1 GENE ON SUBSTRATE BINDING TO PERMEABILITY GLYCOPROTEIN." European Chemical Bulletin 11 (2022), 22-30. doi:10.31838/ecb/2022.11.04.004



MLA (The Modern Language Association) Style

Goutham Yerrakula, Syed Sadathulla T, Kishor GS, Senthil V, Samuel Gideon George P. "EFFECT OF 2677>T/A NON-SYNONYMOUS SINGLE POLYMORPHISM OF HUMAN MDR1 GENE ON SUBSTRATE BINDING TO PERMEABILITY GLYCOPROTEIN." European Chemical Bulletin 11.4 (2022), 22-30. Print. doi:10.31838/ecb/2022.11.04.004



APA (American Psychological Association) Style

Goutham Yerrakula, Syed Sadathulla T, Kishor GS, Senthil V, Samuel Gideon George P (2022) EFFECT OF 2677>T/A NON-SYNONYMOUS SINGLE POLYMORPHISM OF HUMAN MDR1 GENE ON SUBSTRATE BINDING TO PERMEABILITY GLYCOPROTEIN. European Chemical Bulletin, 11 (4), 22-30. doi:10.31838/ecb/2022.11.04.004