In silico modeling of the interaction between TEX19 and LIRE1, and analysis of TEX19 gene missense SNPs

Molecular Genetics & Genomic Medicine

卷:9

Hisham N. Altayeb¹  Faisal A. Alzahrani¹  Hanan E. Alatwi²  Othman R. Alzahrani²  Naif O. Alsiwiehri³  Lamjed Mansour⁴  Suliman Alomar⁴  Osama M. Al‐Amer⁵  Yousef MohammedRabaa Hawsawi⁶ 

[1] Department of Biochemistry Faculty of Science Embryonic Stem Cell Unit King Fahad Center for Medical Research King Abdulaziz University Jeddah Saudi Arabia;

[2] Department of Biology Faculty of Sciences University of Tabuk Tabuk Saudi Arabia;

[3] Department of Clinical Laboratory Science Faculty of Applied Medical Science Taif University Taif Saudi Arabia;

[4] Doping Research Chair Department of Zoology College of Science King Saud University Riyadh Saudi Arabia;

[5] Genome and Biotechnology Unit Faculty of Science University of Tabuk Tabuk Saudi Arabia;

[6] Research Center at King Faisal Specialist Hospital and Research Center Jeddah Saudi Arabia;

关键词: LINE‐1;    MD simulation;    molecular docking;    SNPs analysis;    TEX19;   

DOI  :  10.1002/mgg3.1707

来源: DOAJ

【 摘 要 】

Abstract Background Testis expressed 19 (TEX19) is a specific human stem cell gene identified as cancer‐testis antigen (CTA), which emerged as a potential therapeutic drug target. TEX19.1, a mouse paralog of human TEX19, can interact with LINE‐1 retrotransposable element ORF1 protein (LIRE1) and subsequently restrict mobilization of LINE‐1 elements in the genome. Aim This study aimed to predict the interaction of TEX19 with LIRE1 and analyze TEX19 missense polymorphisms. TEX19 model was generated using I‐TASSER and the interaction between TEX19 and LIRE1 was studied using the HADDOCK software. Methods The stability of the docking formed complex was studied through the molecular dynamic simulation using GROMACS. Missense SNPs (n=102) of TEX19 were screened for their potential effects on protein structure and function using different software. Results Outcomes of this study revealed amino acids that potentially stabilize the predicted interaction interface between TEX19 and LIRE1. Of these SNPs, 37 were predicted to play a probably damaging role for the protein, three of them (F35S, P61R, and E55L) located at the binding site of LIRE1 and could disturb this binding affinity. Conclusion This information can be verified by further in vitro and in vivo experimentations and could be exploited for potential therapeutic targets.

【 授权许可】

Unknown