Functional studies of single-nucleotide polymorphic variants of human glutathione transferase T1-1 involving residues in the dimer interface

2011 ◽  
Vol 513 (2) ◽  
pp. 87-93 ◽  
Author(s):  
P. David Josephy ◽  
Dan Pan ◽  
Michael D. Ianni ◽  
Bengt Mannervik
Keyword(s):  
Glutathione Transferase ◽  
Single Nucleotide Polymorphic ◽  
Single Nucleotide ◽  
Dimer Interface ◽  
Functional Studies ◽  
Polymorphic Variants

Association of genetic polymorphism of cytokines and antioxidant enzymes with the development of asbestosis

2020 ◽  
Vol 60 (12) ◽  
pp. 898-903
Author(s):  
Lyudmila P. Kuzmina ◽  
Anastasiya G. Khotuleva ◽  
Evgeniy V. Kovalevsky ◽  
Nikolay N. Anokhin ◽  
Iraklij M. Tskhomariya
Keyword(s):  
Antioxidant Enzymes ◽  
Genetic Polymorphism ◽  
Genetic Predisposition ◽  
Risk Groups ◽  
Dust Exposure ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Gstp1 Gene ◽  
Polymorphic Variants

Introduction. Various industries widely use chrysotile asbestos, which determines the relevance of research aimed at the prevention of asbestos-related diseases. It is promising to assess the role of specific genes, which products are potentially involved in the development and regulation of certain links in the pathogenesis of asbestosis, forming a genetic predisposition to the disease. The study aims to analyze the presence of associations of genetic polymorphism of cytokines and antioxidant enzymes with asbestosis development. Materials and methods. Groups were formed for examination among employees of OJSC "Uralasbest" with an established diagnosis of asbestosis and without lung diseases. For each person included in the study, dust exposure doses were calculated considering the percentage of time spent at the workplace during the shift for the entire work time. Genotyping of single nucleotide polymorphisms of cytokines IL1b (rs16944), IL4 (rs2243250), IL6 (rs1800795), TNFα (rs1800629) and antioxidant enzymes SOD2 (rs4880), GSTP1 (rs1610011), CAT (rs1001179) was carried out. Results. The authors revealed the associations of polymorphic variants A511G IL1b gene (OR=2.457, 95% CI=1.232-4.899) and C47T SOD2 gene (OR=1.705, 95% CI=1.055-2.756) with the development of asbestosis. There was an increase in the T allele IL4 gene (C589T) frequency in persons with asbestosis at lower values of dust exposure doses (OR=2.185, 95% CI=1.057-4.514). The study showed the associations of polymorphism C589T IL4 gene and C174G IL6 gene with more severe asbestosis, polymorphism A313G GSTP1 gene with pleural lesions in asbestosis. Conclusion. Polymorphic variants of the genes of cytokines and antioxidant enzymes, the protein products directly involved in the pathogenetic mechanisms of the formation of asbestosis, contribute to forming a genetic predisposition to the development and severe course of asbestosis. Using the identified genetic markers to identify risk groups for the development and intense period of asbestos-related pathology will optimize treatment and preventive measures, considering the organism's characteristics.

Rapid determination of trisomy 21 from amniotic fluid cells using single-nucleotide polymorphic loci

2005 ◽  
Vol 25 (12) ◽  
pp. 1138-1141 ◽  
Author(s):  
Bálint Nagy ◽  
Zoltán Bán ◽  
Levente Lázár ◽  
Richárd Gyula Nagy ◽  
Csaba Papp ◽  
...  
Keyword(s):  
Amniotic Fluid ◽  
Trisomy 21 ◽  
Rapid Determination ◽  
Single Nucleotide Polymorphic ◽  
Single Nucleotide ◽  
Polymorphic Loci ◽  
Amniotic Fluid Cells

Genetic association and functional studies of major polymorphic variants of MGMT

DNA Repair ◽  
2007 ◽  
Vol 6 (8) ◽  
pp. 1116-1126 ◽  
Author(s):  
James M. Bugni ◽  
Jiali Han ◽  
Miaw-sheue Tsai ◽  
David J. Hunter ◽  
Leona D. Samson
Keyword(s):  
Genetic Association ◽  
Functional Studies ◽  
Polymorphic Variants

scholarly journals Engineering a Pseudo-26-kDa Schistosoma Glutathione Transferase from bovis/haematobium for Structure, Kinetics, and Ligandin Studies

Biomolecules ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 1844
Author(s):  
Neo Padi ◽  
Blessing Oluebube Akumadu ◽  
Olga Faerch ◽  
Chinyere Aloke ◽  
Vanessa Meyer ◽  
...  
Keyword(s):  
Glutathione Transferase ◽  
Specific Activity ◽  
Enzyme Stability ◽  
Competitive Inhibitor ◽  
Spectroscopic Studies ◽  
Complete Sequence ◽  
Detoxification Enzymes ◽  
Ligand Docking ◽  
Sequence Information ◽  
Dimer Interface

Glutathione transferases (GSTs) are the main detoxification enzymes in schistosomes. These parasitic enzymes tend to be upregulated during drug treatment, with Schistosoma haematobium being one of the species that mainly affect humans. There is a lack of complete sequence information on the closely related bovis and haematobium 26-kDa GST isoforms in any database. Consequently, we engineered a pseudo-26-kDa S. bovis/haematobium GST (Sbh26GST) to understand structure–function relations and ligandin activity towards selected potential ligands. Sbh26GST was overexpressed in Escherichia coli as an MBP-fusion protein, purified to homogeneity and catalyzed 1-chloro-2,4-dinitrobenzene-glutathione (CDNB-GSH) conjugation activity, with a specific activity of 13 μmol/min/mg. This activity decreased by ~95% in the presence of bromosulfophthalein (BSP), which showed an IC50 of 27 µM. Additionally, enzyme kinetics revealed that BSP acts as a non-competitive inhibitor relative to GSH. Spectroscopic studies affirmed that Sbh26GST adopts the canonical GST structure, which is predominantly α-helical. Further extrinsic 8-anilino-1-naphthalenesulfonate (ANS) spectroscopy illustrated that BSP, praziquantel (PZQ), and artemisinin (ART) might preferentially bind at the dimer interface or in proximity to the hydrophobic substrate-binding site of the enzyme. The Sbh26GST-BSP interaction is both enthalpically and entropically driven, with a stoichiometry of one BSP molecule per Sbh26GST dimer. Enzyme stability appeared enhanced in the presence of BSP and GSH. Induced fit ligand docking affirmed the spectroscopic, thermodynamic, and molecular modelling results. In conclusion, BSP is a potent inhibitor of Sbh26GST and could potentially be rationalized as a treatment for schistosomiasis.

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