title: Automated docking of monosaccharide substrates and analogues and methyl alpha-acarviosinide in the glucoamylase active site.
abstract: Glucoamylase is an important industrial glucohydrolase with a large specificity range. To investigate its interaction with the monosaccharides D-glucose, D-mannose, and D-galactose and with the substrate analogues 1-deoxynojirimycin, D-glucono-1,5-lactone, and methyl alpha-acarviosinide, MM3(92)-optimized structures were docked into its active site using AutoDock 2.1. The results were compared to structures of glucoamylase complexes obtained by protein crystallography. Charged forms of some substrate analogues were also docked to assess the degree of protonation possessed by glucoamylase inhibitors. Many forms of methyl alpha-acarviosinide were conformationally mapped by using MM3(92), characterizing the conformational pH dependence found for the acarbose family of glucosidase inhibitors. Their significant conformers, representing the most common states of the inhibitor, were used as initial structures for docking. This constitutes a new approach for the exploration of binding modes of carbohydrate chains. Docking results differ slightly from x-ray crystallographic data, the difference being of the order of the crystallographic error. The estimated energetic interactions, even though agreeing in some cases with experimental binding kinetics, are only qualitative due to the large approximations made by AutoDock force field.
authors.affiliation: Department of Chemical Engineering, Iowa State University, Ames, USA.
authors.forename: P M
authors.initials: PM
authors.lastname: Coutinho
authors.forename: M K
authors.initials: MK
authors.lastname: Dowd
authors.forename: P J
authors.initials: PJ
authors.lastname: Reilly
mesh_terms: D017485:1-Deoxynojirimycin / Q000737:chemistry* / Q000378:metabolism; D001230:Aspergillus / Q000201:enzymology; D001331:Automation; D001665:Binding Sites; D002384:Catalysis; D003198:Computer Simulation; D004187:Disaccharides / Q000737:chemistry* / Q000378:metabolism; D005656:Fungal Proteins / Q000737:chemistry / Q000378:metabolism; D005690:Galactose / Q000737:chemistry* / Q000378:metabolism; D005087:Glucan 1,4-alpha-Glucosidase / Q000737:chemistry* / Q000378:metabolism*; D005942:Gluconates / Q000737:chemistry* / Q000378:metabolism; D005947:Glucose / Q000737:chemistry* / Q000378:metabolism; D007783:Lactones; D008358:Mannose / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D009005:Monosaccharides / Q000737:chemistry / Q000378:metabolism; D013379:Substrate Specificity
chemical_list: D004187:Disaccharides; D005656:Fungal Proteins; D005942:Gluconates; D007783:Lactones; D009005:Monosaccharides; D017485:1-Deoxynojirimycin; D005087:Glucan 1,4-alpha-Glucosidase; D005947:Glucose; D008358:Mannose; C010730:beta-glucono-1,5-lactone; D005690:Galactose