Title : The structure of mammalian β
-mannosidase provides insight into β-mannosidosis and nystagmus
Abstract :
- β -Mannosidase is a lysosomal enzyme from the glycosyl hydrolase family 2 that cleaves the single β (1-4 )-linked mannose at the nonreducing end of N-glycosylated proteins, and plays an important role in the polysaccharide degradation pathway
- Mutations in the MANBA gene, which encodes the β -mannosidase , can lead to the lysosomal storage disease β-mannosidosis, as well as nystagmus, an eye condition characterized by involuntary eye movements
- Here, we present the first structures of a mammalian β -mannosidase in both the apo- and mannose-bound forms
- The structure is similar to previously determined β -mannosidase structures with regard to domain organization and fold, however, there are important differences that underlie substrate specificity between species
- Additionally, in contrast to most other ligand-bound β-mannosidases from bacterial and fungal sources where bound sugars were in a boat-like conformation, we find the mannose in the chair conformation
- Evaluation of known disease mutations in the MANBA gene provides insight into their impact on disease phenotypes
- Together, these results will be important for the design of therapeutics for treating diseases caused by β -mannosidase deficiency
- DATABASE: Structural data are available in the Protein Data Bank under the accession numbers 6DDT and 6DDU