Article
The 1.9 Å structure of human α-N-acetylgalactosaminidase The molecular basis of Schindler and Kanzaki diseases
Journal of Molecular Biology
(2010)
Abstract
alpha-N-acetylgalactosaminidase (alpha-NAGAL; E.C. 3.2.1.49) is a lysosomal exoglycosidase that cleaves terminal alpha-N-acetylgalactosamine residues from glycopeptides and glycolipids. In humans, a deficiency of alpha-NAGAL activity results in the lysosomal storage disorders Schindler disease and Kanzaki disease. To better understand the molecular defects in the diseases, we determined the crystal structure of human alpha-NAGAL after expressing wild-type and glycosylation-deficient glycoproteins in recombinant insect cell expression systems. We measured the enzymatic parameters of our purified wild-type and mutant enzymes, establishing their enzymatic equivalence. To investigate the binding specificity and catalytic mechanism of the human alpha-NAGAL enzyme, we determined three crystallographic complexes with different catalytic products bound in the active site of the enzyme. To better understand how individual defects in the alpha-NAGAL glycoprotein lead to Schindler disease, we analyzed the effect of disease-causing mutations on the three-dimensional structure.
Keywords
- lysosomal storage disease,
- glycoside hydrolase,
- glycoprotein structure,
- human NAGA gene,
- x-ray crystallography
Disciplines
Publication Date
2010
Publisher Statement
This article was harvested from PubMed Central. Please use this link to view the publisher’s version: http://www.sciencedirect.com/science/article/pii/S0022283609009875
Citation Information
Nathaniel E. Clark and Scott Garman. "The 1.9 Å structure of human α-N-acetylgalactosaminidase The molecular basis of Schindler and Kanzaki diseases" Journal of Molecular Biology Vol. 393 Iss. 2 (2010) Available at: http://works.bepress.com/scott_garman/2/