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Automated docking of monosaccharide substrates and analogues and methyl α‐Acarviosinide in the glucoamylase active site
Author(s) -
Coutinho Pedro M.,
Dowd Michael K.,
Reilly Peter J.
Publication year - 1997
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/(sici)1097-0134(199702)27:2<235::aid-prot10>3.0.co;2-n
Subject(s) - docking (animal) , active site , monosaccharide , chemistry , stereochemistry , biochemistry , enzyme , medicine , nursing
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 αacarviosinide, 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 αa‐carviosinide 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 AudoDock force field. © 1997 Wiley‐Liss, Inc.