Three dimensional structural studies of α-N-acetylgalactosaminidase (α-NAGA) in α-NAGA deficiency (Kanzaki disease): different gene mutations cause peculiar structural changes in α-NAGAs resulting in different substrate specificities and clinical phen

Our findings suggest that the association of α-NAGA with its substrates is strongly affected by the amino acid substitution at R329 and that the association with GalNAcα1-O-Thr is more highly susceptible to structural changes. The residual mutant enzyme in R329W could not associate with GalNAcα1-O-Thr and GalNAcα1-O-Ser. However, the residual mutant enzyme in R329Q catalyzed GalNAcα1-O-Ser to some extent. Therefore, the urinary ratio of GalNAcα1-O-Ser:GalNAcα1-O-Thr was lower and the clinical phenotype was milder in the R329Q mutation. Structural analysis revealed biochemical and phenotypic differences in these Kanzaki patients with the R329Q and R329W mutation.