A xylobiose-derived isofagomine lactam glycosidase inhibitor binds as its amide tautomer.
The atomic-resolution structure of a xylobiose-derived isofagomine lactam in complex with the xylanase Xyn10A from Streptomyces lividans reveals that the lactam is bound to the enzyme as the amide tautomer, with "reversed" protonation-states for nucleophile and acid-base.
Gloster
Tracey
T
Structural Biology Laboratory, Department of Chemistry, The University of York, Heslington, UK.
Williams
Spencer J
SJ
Tarling
Chris A
CA
Roberts
Shirley
S
Dupont
Claude
C
Jodoin
Pascalé
P
Shareck
François
F
Withers
Stephen G
SG
Davies
Gideon J
GJ
D000577:Amides / Q000737:chemistry*; D001667:Binding, Competitive; D018360:Crystallography, X-Ray; D004187:Disaccharides / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D006026:Glycoside Hydrolases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D050112:Imino Pyranoses; D007769:Lactams / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D008958:Models, Molecular; D010880:Piperidines / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D013302:Streptomyces / Q000201:enzymology; D043325:Xylan Endo-1,3-beta-Xylosidase; D014995:Xylosidases / Q000378:metabolism
D000577:Amides; D004187:Disaccharides; D004791:Enzyme Inhibitors; D050112:Imino Pyranoses; D007769:Lactams; D010880:Piperidines; C098432:isofagomine; D006026:Glycoside Hydrolases; D014995:Xylosidases; D043325:Xylan Endo-1,3-beta-Xylosidase; C004173:xylobiose