کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1985716 1540231 2016 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Fasciola gigantica thioredoxin glutathione reductase: Biochemical properties and structural modeling
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Fasciola gigantica thioredoxin glutathione reductase: Biochemical properties and structural modeling
چکیده انگلیسی


• The recombinant thioredoxin glutathione reductase of Fasciola gigantica exists in a dimeric state in solution.
• The enzymatic constants for FgTGR were found comparable with other reported TGRs.
• Molecular docking studies suggested binding sites for substrates and co-factors.
• Site-2 was found to be more favorable for substrate binding.

Platyhelminth thioredoxin glutathione reductase (TGR) is a multifunctional enzyme that crosstalk between the conventional thioredoxin (Trx) and glutathione (GSH) system. It has been validated as a potential drug target in blood flukes. In the present study, we have performed a biochemical study on Fasciola gigantica TGR with substrates DTNB and GSSG. The Michaelis constant (Km) with DTNB was found to be 4.34 ± 0.12 μM while it was 61.15 ± 1.50 μM with GSSG. The kinetic results were compared with the TGR activities of other helminths. FgTGR showed typical hysteretic behavior with GSSG as other TGRs. We also described a homology-based structure of FgTGR. The cofactors (NADPH and FAD) and substrates (GSSG and DTNB) were docked, and two possible binding sites for substrates were identified in a single chain. The substrates were found to bind more favorably in the second site of TrxR domains. We also presented the first report on binding interaction of DTNB with a TGR. DTNB forms H-bond with His204 and Arg450 of chain A, Sec597, and Gly598 from chain B, salt-bridge with Lys124, and numerous other hydrophobic interactions. Helminth TGR represents an important enzyme in the redox and antioxidant system; hence, its inhibition can be used as an effective strategy against liver flukes.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: International Journal of Biological Macromolecules - Volume 89, August 2016, Pages 152–160
نویسندگان
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