Three-dimensional structure of human lysosomal aspartylglucosaminidase.
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.
Oinonen
C
C
Department of Chemistry, University of Joensuu, Finland.
Tikkanen
R
R
Rouvinen
J
J
Peltonen
L
L
D001227:Aspartylglucosylaminase / Q000737:chemistry* / Q000648:ultrastructure; D006801:Humans; D008024:Ligands; D008247:Lysosomes / Q000737:chemistry / Q000201:enzymology*; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary
D008024:Ligands; D001227:Aspartylglucosylaminase