Abstract
The glycoside hydrolases are a large group of enzymes that can be grouped into two major mechanistic classes based upon the stereochemical outcome of catalysis: retention and inversion of sugar anomeric configuration. Both mechanisms involve nucleophilic displacement at the anomeric center, and both proceed via positively charged oxocarbenium ion-like transition states. Exceptions to this are the Family 4 glycoside hydrolases (GH4), which display an unusual requirement for NAD+ and a divalent metal for activity. In addition, Family 4, uniquely, contains both α- and β-glycosidases. A novel mechanism is proposed for all GH4 members, featuring a redox-elimination-addition sequence, and involving anionic transition states to effect hydrolytic cleavage of the glycosidic linkage.
Notes
1Although Family 39 glycosidases, which includes both α-L-iduronidases and β-D-xylosidases, also appear to be an exception to this rule, the anomeric configurations of the substrates are the same. The α/β switch seen is a consequence of nomenclature rules associated with the D/L configuration differences in the substrates.