Thioredoxin system: a model for determining novel lead molecules for breast Cancer chemotherapy

Thioredoxin reductase 1 [TXNRD1] and thioredoxin interacting protein [TXNIP] also known as thioredoxin binding protein 2 or vitamin D3-upregulated protein 1 are key players in oxidative stress control. Thioredoxin [TRX] is one of the major components of the thiol reducing system and plays multiple roles in cellular processes. Computational analyses of TXNRD1, TXNIP and TRX expressions have not been analyzed in relation to prognosis of breast cancer. High expression of TXNRD1 and low expression of TXNIP are associated with worst prognosis in breast cancer. Using bioinformatics applications we studied sequence analysis, molecular modeling, template and fold recognition, docking and scoring of thioredoxin as a target. The resultant model obtained was validated based on the templates from I-TASSER server and binding site residues were predicted. The predicted model was used for Threading and Fold recognition and was optimized using GROMACS. The generated model was validated using programs such as Procheck, Ramachandran plot, verify-3d and Errat value from Saves server, and the results show that the model is reliable. Next we obtained small molecules from pubchem and chembank which are databases for selecting suitable ligands for our modeled target. These molecules were screened for docking, using GOLD and scoring was obtained using Chemscore as a scoring function. This study predicted the ligand interaction of four molecules with the minimized protein modeled structure and the best ligand with top scores from about 500 molecules screened. These were 3-hydroxy-2,3-diphenylbutanoic acid, 4-amino-3-pentadecylphenol, 3-[hydroxyimino]-2,4-diphenylbutanenitrile and 2-ethyl-1,2-diphenylbutyl carbamate, which are proposed as possible hit molecules for the drug discovery and development process

TrxR2 gene polymorphisms may not be associated with the susceptibility to Kashin-Beck disease / 南方医科大学学报

<p><b>OBJECTIVE</b>To study the association between single nucleotide polymorphisms of thioredoxin reductase-2 (TrxR2) gene and the susceptibility to Kashin-Beck disease (KBD).</p><p><b>METHODS</b>Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to analyze the genotype frequencies of rs5748469 in TrxR2 gene in 84 KBD patients and 109 healthy control subjects.</p><p><b>RESULTS</b>The genotype frequencies of A/A, A/C, and C/C in the KBD patients were 83.33%, 15.48% and 1.19%, as compared with the frequencies of 74.31%, 25.69%, and 0.00% in the healthy control, respectively, showing no significant difference in the single nucleotide polymorphisms of TrxR2 gene between the two groups (P=0.13).</p><p><b>CONCLUSION</b>No obvious correlation can be found between rs5748469 polymorphisms in TrxR2 gene and the susceptibility to KBD.</p>

Association of genetic polymorphisms in selenoprotein GPX1 and TXNRD2 with genetic susceptibility of gastric cancer / 中华预防医学杂志

<p><b>OBJECTIVE</b>This study examined whether the two polymorphisms of GPX1 (198Pro--> Leu) and TXNRD2 (370Lys-->Arg) contributed alone or in combination, to the risk of gastric cancer development.</p><p><b>METHODS</b>A total of 361 patients with gastric cancer and 363 cancer-free controls were recruited and their genotypes of the two polymorphisms were determined by polymerase chain reaction-based restrictive fragment length polymorphism (PCR-RFLP) method. Odds ratio (OR) and 95% confidence interval (CI) were computed using unconditional logistic regression model.</p><p><b>RESULTS</b>GPX1 and TXNRD2 polymorphisms individually were not associated with the risk of gastric cancer. Gene-gene interaction of GPX1 and TXNRD2 polymorphisms decreased the risk of gastric cancer. Carrying the protective genotype might decrease the risk at 62% (OR = 0.38, 95% CI = 0.26-0.55, P < 0.001) as compared with the risk genotype.</p><p><b>CONCLUSION</b>The GPX1 198 Pro/Pro and TXNRD2 370Arg/Arg genotypes might be associated with the genetic susceptibility of gastric cancer.</p>