3H55

Crystal Structure of human alpha-N-acetylgalactosaminidase, Complex with Galactose

Summary for 3H55

• Entry DOI: 10.2210/pdb3h55/pdb
• Related: 3H53 3H54
• Descriptor: Alpha-N-acetylgalactosaminidase, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose, alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (8 entities in total)
• Functional Keywords: glycoprotein, carbohydrate-binding protein, glycosidase, lysosomal enzyme, (beta/alpha)8 barrel, protein-ligand complex, disease mutation, disulfide bond, hydrolase, lysosome
• Biological source: Homo sapiens (Human)
• Cellular location: Lysosome: P17050
• Total number of polymer chains: 2
• Total formula weight: 95837.89

Authors

Clark, N.E.,Garman, S.C. (deposition date: 2009-04-21, release date: 2009-10-20, Last modification date: 2023-09-06)

Primary citation

Clark, N.E.,Garman, S.C.
The 1.9 a structure of human alpha-N-acetylgalactosaminidase: The molecular basis of Schindler and Kanzaki diseases
J.Mol.Biol., 393:435-447, 2009

PubMed 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.

PubMed: 19683538
DOI: 10.1016/j.jmb.2009.08.021

Experimental method

X-RAY DIFFRACTION (1.91 Å)