Loss of phosphatase activity in PTEN (phosphatase and tensin homolog deleted on chromosome ten) results in endometrial carcinoma in humans: An in-silico study

Heliyon

Madhab Kumar Sen¹  Sunil Kanti Mondal² 

[1] Corresponding author.;Department of Biotechnology, The University of Burdwan, Burdwan, 713104, West Bengal, India;

关键词: Systems biology;    Bioinformatics;    Biotechnology;    Molecular biology;    Tumour suppressor gene;    PTEN;   

DOI  :  

来源: DOAJ

【 摘 要 】

The tumour suppressor gene, PTEN (Phosphatase and Tensin homolog deleted on chromosome Ten), can act as both protein phosphatase and lipid phosphatase, is known to play a vital role in Pi3k signalling pathway. In humans, it is located at 10q23. Loss of its phosphatase and catalytic activity is associated with various types of cancers. This study focuses on evolution, understanding the somatic missense mutation in a particular residue of PTEN and understanding the molecular mechanism that leads to endometrial carcinoma through molecular docking. Mutational analysis of H123 position indicates that the missense mutation at first position of the codon CAC by G or T, result in aspartic acid or tyrosine instead of histidine and can have negative effect on the function of PTEN. Alongside, structural analysis showed mutated PTEN has lower stability than the normal. Additionally, SNPs dataset for endometrial carcinoma suggests H123 as strongly mutated residue. The mutation in phosphatase domain of PTEN along with its effect and interaction with substrate TLA1352 were systematically studied through molecular docking. Molecular interaction study reveals that the optimal substrate binding site in PTEN is unable to interact with the substrate in the mutated condition. This observation drew attention on the impact of mutation on disease biology and enabled us to conduct follow-up studies to retrieve novel molecular targets, such as mutated protein domain and modified Asp and Tyr sites, to design effective therapies to either prevent endometrial carcinoma or impede its progression.

【 授权许可】

Unknown