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Common Inhibition of Both β‐Glucosidases and β‐Mannosidases by Isofagomine Lactam Reflects Different Conformational Itineraries for Pyranoside Hydrolysis
Author(s) -
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.
Publication year - 2004
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.200400169
Subject(s) - glucosidases , glycoside hydrolase , mannosidase , stereochemistry , enzyme , hydrolase , chemistry , hydrolysis , lactam , biochemistry
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 B 2,5 conformation for some retaining mannosidases and the 4 H 3 for glucosidases, both of which place O2 pseudo‐equatorially.