Overview of structure-function relationships of glucuronidases

Glucuronic acid (GlcA) is component of proteoglycans, glycosaminoglycans, xylans, and numerous endogenous and xenobiotic glycosides. Glucuronidases hydrolyze the glycosidic bond between GlcA and either a carbohydrate or a noncarbohydrate moiety and are of significance for biofuel, medical and biochemical applications. They are dispersed across all taxonomic groups and have evolved substantial differences in their biochemical properties. Glucuronidases can be classified into α-glucuronidases and β-glucuronidases. α-Glucuronidases that adopt the inverting mechanism are harbored in the glycosyl hydrolase (GH) families 67 and 115 in the Carbohydrate Active enZyme (CAZy) database. β-Glucuronidases that are classified into GH families 1, 2, 30, 79, 154, and 169, employ the retaining mechanism. All glucuronidases within these families share a catalytic domain comprising a (β/α)8-barrel fold, although individual enzymes may contain additional domains. The unique GH4 family α-glucuronidase contains a modified Rossmann fold and utilizes a distinctive metal- and NAD (H)-dependent redox-based multistep mechanism involving elimination-addition via anionic intermediate states. An overview of literature directed at the characterization of the structure-function relationships of glucuronidases is presented.