Distortion of a cellobio-derived isofagomine highlights the potential conformational itinerary of inverting beta-glucosidases.
A cellobio-derived isofagomine glycosidase inhibitor (Ki approximately 400 nM) displays an unusual distorted 2,5B (boat) conformation upon binding to cellobiohydrolase Cel6A from Humicola insolens, highlighting the different conformational itineraries used by various glycosidases, with consequences for the design of therapeutic agents.
Structural Biology Laboratory, Department of Chemistry, The University of York, Heslington, York, UK Y010 5YW.
Annabelle
A
Varrot
James
J
Macdonald
Robert V
RV
Stick
Gavin
G
Pell
Harry J
HJ
Gilbert
Gideon J
GJ
Davies
D001203:Ascomycota / Q000201:enzymology; D002475:Cellobiose / Q000031:analogs & derivatives* / Q000378:metabolism; D002480:Cellulase / Q000737:chemistry / Q000378:metabolism; D043366:Cellulose 1,4-beta-Cellobiosidase; D006026:Glycoside Hydrolases / Q000037:antagonists & inhibitors; D050112:Imino Pyranoses; D008958:Models, Molecular; D010880:Piperidines / Q000737:chemistry* / Q000378:metabolism; D011487:Protein Conformation; D013379:Substrate Specificity; D001617:beta-Glucosidase / Q000737:chemistry*
D050112:Imino Pyranoses; D010880:Piperidines; C098432:isofagomine; D002475:Cellobiose; D006026:Glycoside Hydrolases; D001617:beta-Glucosidase; D002480:Cellulase; D043366:Cellulose 1,4-beta-Cellobiosidase