title: Probing the binding of Syzygium-derived α-glucosidase inhibitors with N- and C-terminal human maltase glucoamylase by docking and molecular dynamics simulation.
abstract: Human maltase glucoamylase (MGAM) is a potent molecular target for controlling post prandial glucose surplus in type 2 diabetes. Binding of small molecules from Syzygium sp. with α-glucosidase inhibitory potential in MGAM has been investigated in silico. Our results suggest that myricetin was the most potent inhibitor with high binding affinity for both N- and C-terminals of MGAM. Molecular dynamics revealed that myricetin interacts in its stretched conformation through water-mediated interactions with C-terminal of MGAM and by normal hydrogen bonding with the N-terminal. W1369 of the extended 21 amino acid residue helical loop of C-terminal plays a major role in myricetin binding. Owing to its additional sugar sites, overall binding of small molecules favours C-terminal MGAM.
authors.affiliation: 206, Structural Biology Lab, Centre for Biomedical Research, School of Bio Sciences & Technology, VIT University, Vellore, 632014, Tamil Nadu, India.
authors.forename: Debasish
authors.initials: D
authors.lastname: Roy
authors.forename: Vinod
authors.initials: V
authors.lastname: Kumar
authors.forename: Kshitish K
authors.initials: KK
authors.lastname: Acharya
authors.forename: Kavitha
authors.initials: K
authors.lastname: Thirumurugan
mesh_terms: D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D065089:Glycoside Hydrolase Inhibitors; D006801:Humans; D007004:Hypoglycemic Agents / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D011487:Protein Conformation; D054852:Small Molecule Libraries / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D013379:Substrate Specificity; D027842:Syzygium / Q000737:chemistry*; D000520:alpha-Glucosidases / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; D065089:Glycoside Hydrolase Inhibitors; D007004:Hypoglycemic Agents; D054852:Small Molecule Libraries; D000520:alpha-Glucosidases