3H54

Crystal Structure of human alpha-N-acetylgalactosaminidase,complex with GalNAc

3H54 の概要

• エントリーDOI: 10.2210/pdb3h54/pdb
• 関連するPDBエントリー: 3H53 3H55
• 分子名称: 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)
• 機能のキーワード: glycoprotein, carbohydrate-binding protein, glycosidase, lysosomal enzyme, (beta/alpha)8 barrel, protein-ligand complex, disease mutation, disulfide bond, hydrolase, lysosome
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Lysosome: P17050
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 96556.85

構造登録者

Clark, N.E.,Garman, S.C. (登録日: 2009-04-21, 公開日: 2009-10-20, 最終更新日: 2024-11-20)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.2 Å)