title: The kinetics and mechanism of α-glucosidase inhibition by F5-SP, a novel compound derived from sericin peptides.
abstract: The inhibition of α-glucosidase decreases postprandial blood glucose and therefore plays an important role in the treatment of type 2 diabetes mellitus. The present study investigated and characterized a peptide fraction of sericin hydrolysate, the kinetics of peptide-induced inhibition of α-glucosidase, and the interaction mechanism between the peptides and α-glucosidase. The fraction that eluted with 0.4 M NaCl (F5-SPs) on a DEAE-cellulose column exhibited significant inhibitory activity with an IC50of 41 ± 1.94 μg mL-1. A kinetics analysis revealed that the F5-SP-induced inhibition was a reversible and parabolic mixed-type inhibition with a Kivalue of 86.63 ± 0.014 μg mL-1. F5-SPs can bind to α-glucosidase at multiple sites to alter the conformation of α-glucosidase. F5-SPs were found to be rich in Gly, Ser, Glu, Tyr, Arg, and Pro, and had a sericin-conserved sequence SEDSSEVDIDLGNLG, as analyzed by Nano LC-MS/MS. Fluorescence spectra analysis showed that F5-SPs quenched the intrinsic fluorescence of α-glucosidase by a static quenching mechanism, and circular dichroism analysis suggested that the binding of F5-SPs to α-glucosidase resulted in the alteration of the secondary structure of an enzyme. The results of this study support the dietary recommendation of F5-SPs for the treatment of type 2 diabetes.
authors.affiliation: Department of Food Science and Engineering, Shanghai Food Safety and Engineering Research Center, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240, China. wujinhong@sjtu.edu.cn.
authors.forename: Yuwen
authors.initials: Y
authors.lastname: Fang
authors.affiliation: College of Biological Science and Engineering, Fuzhou University, Fuzhou 350108, China.
authors.forename: Shaoyun
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Food Science and Engineering, Shanghai Food Safety and Engineering Research Center, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240, China. wujinhong@sjtu.edu.cn.
authors.forename: Jinhong
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Food Science and Engineering, Shanghai Food Safety and Engineering Research Center, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240, China. wujinhong@sjtu.edu.cn.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Food Science and Engineering, Shanghai Food Safety and Engineering Research Center, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240, China. wujinhong@sjtu.edu.cn.
authors.forename: Zhengwu
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Food Science and Engineering, Shanghai Food Safety and Engineering Research Center, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240, China. wujinhong@sjtu.edu.cn.
authors.forename: Li
authors.initials: L
authors.lastname: Gan
authors.affiliation: Department of Food Science and Engineering, Shanghai Food Safety and Engineering Research Center, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240, China. wujinhong@sjtu.edu.cn.
authors.forename: Jiajun
authors.initials: J
authors.lastname: He
authors.affiliation: Department of Food Science and Engineering, Shanghai Food Safety and Engineering Research Center, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240, China. wujinhong@sjtu.edu.cn.
authors.forename: Haiming
authors.initials: H
authors.lastname: Shi
authors.affiliation: Department of Food Science and Engineering, Shanghai Food Safety and Engineering Research Center, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240, China. wujinhong@sjtu.edu.cn.
authors.forename: Jingli
authors.initials: J
authors.lastname: Hou
mesh_terms: D065089:Glycoside Hydrolase Inhibitors / Q000737:chemistry*; D007700:Kinetics; D013058:Mass Spectrometry; D010449:Peptide Mapping; D010455:Peptides / Q000737:chemistry*; D012441:Saccharomyces cerevisiae / Q000201:enzymology*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000378:metabolism; D047030:Sericins / Q000737:chemistry*; D000520:alpha-Glucosidases / Q000737:chemistry* / Q000378:metabolism
chemical_list: D065089:Glycoside Hydrolase Inhibitors; D010455:Peptides; D029701:Saccharomyces cerevisiae Proteins; D047030:Sericins; D000520:alpha-Glucosidases