An unusual mechanism of glycoside hydrolysis involving redox and elimination steps by a family 4 beta-glycosidase from Thermotoga maritima

J Am Chem Soc. 2004 Jul 14;126(27):8354-5. doi: 10.1021/ja047632w.


Among the numerous well-characterized families of glycosidases, family 4 appears to be the anomaly, requiring both catalytic NAD+ and a divalent metal for activity. The unusual cofactor requirement prompted the proposal of a mechanism involving key NAD+-mediated redox steps as well as elimination of the glycosidic oxygen. Primary kinetic isotope effects for the 2- and 3-deutero substrate analogues, isotopic exchange with solvent, and structural analysis of a 6-phospho-beta-glucosidase, BglT (E.C., provided evidence in support of the proposed mechanism, which has striking resemblances to that of the sugar dehydratases. Furthermore, analysis of the stereochemical outcome indicated that family 4 enzymes are retaining glycosidases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Glucosidases / chemistry*
  • Glucosidases / metabolism*
  • Glycosides / chemistry*
  • Glycosides / metabolism*
  • Hydrolysis
  • Models, Molecular
  • Oxidation-Reduction
  • Thermotoga maritima / enzymology*


  • Glycosides
  • Glucosidases
  • 6-phospho-beta-glucosidase