Journal article
Selection of a high-energy bioactive conformation of a sulfonium-ion glycosidase inhibitor by the enzyme glucoamylase G2
Transferred nuclear Overhauser effect and rotating-frame Overhauser enhancement NMR spectroscopies are used to probe the conformation of a bicyclic sulfonium ion, which is an analogue of the naturally occurring glycosidase inhibitor castanospermine, bound to the enzyme glucoamylase G2. Enzyme inhibition assays indicate that the bicyclic sulfonium ion is a slightly better inhibitor (K(i) = 1.32 mM) of glucoamylase G2 than the naturally occurring sulfonium-ion glycosidase inhibitor, salacinol, with a K(i) value of 1.7 mM.
The NMR results are interpreted in terms of the selection by the enzyme of a high-energy conformation of the ligand that is already represented in the ensemble of free-ligand conformations.
Language: | English |
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Year: | 2003 |
Pages: | 5663-5670 |
ISSN: | 15205126 and 00027863 |
Types: | Journal article |
DOI: | 10.1021/ja0212617 |
Binding, Competitive Bridged Bicyclo Compounds, Heterocyclic Carbohydrate Sequence Enzyme Inhibitors Glucan 1,4-alpha-Glucosidase Indolizines Models, Molecular Molecular Conformation Molecular Sequence Data Nuclear Magnetic Resonance, Biomolecular Protein Conformation Sulfonium Compounds Thermodynamics castanospermine