Common Inhibition of Both β-Glucosidases and β-Mannosidases by Isofagomine Lactam Reflects Different Conformational Itineraries for Pyranoside Hydrolysis

Glycosidase inhibition is a key process both in the pursuit of new therapeutic agents and in the drive to understand transition‐state stabilisation by these remarkable enzymes. That isofagomine lactam (1) is an equally potent inhibitor of β‐glucosidases and β‐mannosidases (despite possessing a carbo...

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Published in:Chembiochem : a European journal of chemical biology 2004-11, Vol.5 (11), p.1596-1599
Main Authors: Vincent, Florence, Gloster, Tracey M, Macdonald, James, Morland, Carl, Stick, Robert V, Dias, Fernando M.V, Prates, José A.M, Fontes, Carlos M.G.A, Gilbert, Harry J, Davies, Gideon J
Format: Article
Language:English
Subjects:
beta-Mannosidase - antagonists & inhibitors
beta-Mannosidase - chemistry
Biochemistry, Molecular Biology
Biophysics
carbohydrates
Cellulases - antagonists & inhibitors
Cellulases - chemistry
enzyme catalysis
Enzyme Inhibitors - pharmacology
glycosides
Hydrolysis
Imino Pyranoses
inhibitors
Kinetics
lactams
Lactams - pharmacology
Life Sciences
Molecular biology
Molecular Conformation
Piperidines - pharmacology
Pyrans - chemistry
Structural Biology
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Summary:Glycosidase inhibition is a key process both in the pursuit of new therapeutic agents and in the drive to understand transition‐state stabilisation by these remarkable enzymes. That isofagomine lactam (1) is an equally potent inhibitor of β‐glucosidases and β‐mannosidases (despite possessing a carbonyl group) adds to the emerging view that mannosidases and glucosidases harness distinct transition states; the B2,5 conformation for some retaining mannosidases and the 4H3 for glucosidases, both of which place O2 pseudo‐equatorially.
ISSN:1439-4227
1439-7633
DOI:10.1002/cbic.200400169