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A bioactive polypeptide from sugarcane selectively inhibits intestinal sucrase.

Shaik, Abduldileep and Narayanasamy, Raja and Usharani, D. and Ajeet, Singh and Ram, Rajasekharan (2020) A bioactive polypeptide from sugarcane selectively inhibits intestinal sucrase. International Journal of Biological Macromolecules, 156. pp. 938-948. ISSN 0141-8130

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Human sucrase enzyme is a key therapeutic target for type 2 diabetes. While sugarcane sucrase inhibitor (sucinh) modulates invertase activity thereby accumulates sucrose. Molecular level understanding of sucinh towards mammalian α-glucosidases is scarce. The interaction of sucinh with human sucrase was identified and the association of these proteins was confirmed using co-purification, co-immunoprecipitation and pull-down assay. In addition, microscale thermophoresis assay showed that sucinh has a tight binding with sucrase (Kd = 4.77 nM) and a better affinity over acarbose. Collectively, in vitro, ex vivo and in silico data revealed that sucinh is selective for intestinal sucrase. The M region (H5/6 loop) of sucinh identified at the protein-protein interface is shown to have high affinity over N and C regions. Whereas, the biolayer luminescent imaging and microscale thermophoresis on the synthetic peptide of 28 amino acids of M region has a weak dose-dependent binding with sucrase. However, the synthetic peptide did not show substantial inhibition of sucrase and amylase activities at low concentration. Naturally derived carbohydrate mimics were shown to have a positive impact at the in vitro conditions. The insights obtained in this study give clues towards a new class of bioactive therapeutic peptides for α-glucosidases. A new horizon towards polypeptides derived from food sources emerge as a promising strategy for dietary interventions for prediabetic conditions.

Item Type: Article
Uncontrolled Keywords: Sucrase Plant invertase inhibitor α-Glucosidases MM/GBSA Protein-protein interactions Acarbose
Subjects: 600 Technology > 08 Food technology > 16 Nutritive value > 05 Enzymes
600 Technology > 08 Food technology > 25 Sugar/Starch/Confectionery
Divisions: Dept. of Lipid Science
Depositing User: Food Sci. & Technol. Information Services
Date Deposited: 27 Nov 2020 09:29
Last Modified: 27 Nov 2020 09:29
URI: http://ir.cftri.res.in/id/eprint/14663

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