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.
Varrot
Annabelle
A
Structural Biology Laboratory, Department of Chemistry, The University of York, Heslington, York, UK Y010 5YW.
Macdonald
James
J
Stick
Robert V
RV
Pell
Gavin
G
Gilbert
Harry J
HJ
Davies
Gideon J
GJ
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