Title : Three-dimensional structure of human lysosomal
aspartylglucosaminidase
Abstract :
- The high resolution crystal structure of human lysosomal aspartylglucosaminidase ( AGA ) has been determined
- This lysosomal enzyme is synthesized as a single polypeptide precursor , which is immediately post-translationally cleaved into alpha- and beta- subunits
- Two alpha- and beta- chains are found to pack together forming the final heterotetrameric structure
- The catalytically essential residue , the N-terminal threonine of the beta- chain is situated in the deep pocket of the funnel-shaped active site
- On the basis of the structure of the enzyme-product complex we present a catalytic mechanism for this lysosomal enzyme with an exceptionally high pH optimum
- The three-dimensional structure also allows the prediction of the structural consequences of human mutations resulting in aspartylglucosaminuria (AGU), a lysosomal storage disease