Abstract
The title compound, a powerful inhibitor of retaining N-acetylhexosaminidases, can move freely among three pyranose solution conformations of similar energy-two twist boats and the (4)C(1) chair-as revealed by NMR, calculational, and crystallographic studies. It binds in the enzyme active site only in the pseudo-(4)C(1) conformation, however, in which it most closely resembles the hypothetical bound substrate transition state, a (4)E sofa that is approximately trigonal bipyramidal at the anomeric carbon.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Crystallography, X-Ray
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Enzyme Inhibitors / chemistry
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Glucosamine / analogs & derivatives*
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Glucosamine / chemistry
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Magnetic Resonance Spectroscopy
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Molecular Conformation
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Thermodynamics
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Thiazoles / chemistry*
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beta-N-Acetylhexosaminidases / antagonists & inhibitors
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beta-N-Acetylhexosaminidases / chemistry
Substances
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Enzyme Inhibitors
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GlcNAc-thiazoline
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Thiazoles
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hexosaminidase C
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beta-N-Acetylhexosaminidases
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Glucosamine