InterPro domain: IPR006775

This entry represents the catalytic region found in the CAZyme GH116 family members, which presently includes enzymes with beta-glucosidase ( 3.2.1.21 ), beta-xylosidase ( 3.2.1.37 ) , and glucocerebrosidase ( 3.2.1.45 ) activity [ 1 ]. Proteins containing this domain include animal non-lysosomal glucosylceramidase GBA2, which catalyse the conversion of glucosylceramide to free glucose and ceramide [ 2 ]. GBA2 is involved in sphingomyelin generation and prevention of glycolipid accumulation and may also catalyse the hydrolysis of bile acid 3-O-glucosides, however, the relevance of such activity is unclear in vivo [ 3 ]. Mutations in the human protein cause motor-neurone defects in hereditary spastic paraplegia [ 4 ]. The catalytic nucleophile, identified in Q97YG8 is a glutamine-335, with the likely acid/base at Asp-442 and the aspartates at Asp-406 and Asp-458 residues also playing a role in the catalysis of glucosides and xylosides that are beta-bound to hydrophobic groups [ 5 ].

1. A new archaeal beta-glycosidase from Sulfolobus solfataricus: seeding a novel retaining beta-glycan-specific glycoside hydrolase family along with the human non-lysosomal glucosylceramidase GBA2. J. Biol. Chem. 285, 20691-703
2. Identification of the non-lysosomal glucosylceramidase as beta-glucosidase 2. J. Biol. Chem. 282, 1305-12
3. Mutation of beta-glucosidase 2 causes glycolipid storage disease and impaired male fertility. J. Clin. Invest. 116, 2985-94
4. Mutations in GBA2 cause autosomal-recessive cerebellar ataxia with spasticity. Am. J. Hum. Genet. 92, 245-51