کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
8328831 1540207 2018 12 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Inhibitory mechanism of two allosteric inhibitors, oleanolic acid and ursolic acid on α-glucosidase
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Inhibitory mechanism of two allosteric inhibitors, oleanolic acid and ursolic acid on α-glucosidase
چکیده انگلیسی
Glycemic control which can be efficaciously regulated by inhibiting α-glucosidase activity is an effective therapy for diabetes mellitus. This work is to investigate the kinetics and inhibition mechanism of oleanolic acid and ursolic acid on α-glucosidase. Oleanolic acid and ursolic acid exhibited potent inhibitory activities with IC50 values of (6.35 ± 0.02) × 10−6 and (1.69 ± 0.03) × 10−5 mol L−1 respectively in a reversible and non-competitive manner. Both of them binding to α-glucosidase induced the conformational change and intrinsic fluorescence quenching of α-glucosidase. The binding constants of oleanolic acid and ursolic acid with α-glucosidase at 298 K were (2.04 ± 0.02) × 103 and (1.87 ± 0.02) × 103 L mol−1, respectively. Docking results showed that oleanolic acid and ursolic acid bound in different allosteric sites of cavity 2 and cavity 4 on α-glucosidase, respectively, which triggered allosteric regulation to perturb conformational dynamics of α-glucosidase, eventually leading to a decrease of catalytic activity of the enzyme. The substrate was not catalyzed by α-glucosidase to generate further products due to formation of a nonreactive ternary complex of oleanolic acid- or ursolic acid-α-glucosidase-substrate. The combination of oleanolic acid and ursolic acid displayed a significant synergistic inhibition on α-glucosidase.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: International Journal of Biological Macromolecules - Volume 107, Part B, February 2018, Pages 1844-1855
نویسندگان
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