Distortion of a cellobio-derived isofagomine highlights the potential conformational itinerary of inverting beta-glucosidases

Chem Commun (Camb). 2003 Apr 21:(8):946-7. doi: 10.1039/b301592k.

Abstract

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.

MeSH terms

  • Ascomycota / enzymology
  • Cellobiose / analogs & derivatives*
  • Cellobiose / metabolism
  • Cellulase / chemistry
  • Cellulase / metabolism
  • Cellulose 1,4-beta-Cellobiosidase
  • Glycoside Hydrolases / antagonists & inhibitors
  • Imino Pyranoses
  • Models, Molecular
  • Piperidines / chemistry*
  • Piperidines / metabolism
  • Protein Conformation
  • Substrate Specificity
  • beta-Glucosidase / chemistry*

Substances

  • Imino Pyranoses
  • Piperidines
  • isofagomine
  • Cellobiose
  • Glycoside Hydrolases
  • beta-Glucosidase
  • Cellulase
  • Cellulose 1,4-beta-Cellobiosidase