-
- 清水 敏之
- 東京大学大学院薬学系研究科
書誌事項
- タイトル別名
-
- Structural Basis for β-Galactosidase Associated with Lysosomal Disease
- リソソームビョウ ゲンイン タンパクシツv-ガラクトシダーゼ ノ コウゾウ キバン
この論文をさがす
抄録
GM1-gangliosidosis and Morquio B are rare lysosomal storage diseases associated with a neurodegenerative disorder or dwarfism and skeletal abnormalities, respectively. These diseases are caused by deficiencies in the lysosomal enzyme human β-D-galactosidase (h-β-GAL), which lead to accumulations of the h-β-GAL substrates, GM1 ganglioside and keratan sulfate due to mutations in the h-β-GAL gene. H-β-GAL is an exoglycosidase that catalyzes the hydrolysis of terminal β-linked galactose residues. Here, we present the crystal structures of h-β-GAL in complex with its catalytic product galactose or with its inhibitor 1-deoxygalactonojirimycin. H-β-GAL showed a novel homodimer structure; each monomer was comprised of a catalytic TIM barrel domain followed by β-domain 1 and β-domain 2. The long loop region connecting the TIM barrel domain with β-domain 1 was responsible for the dimerization. To gain structural insight into the molecular defects of h-β-GAL in the above diseases, the disease-causing mutations were mapped onto the three-dimensional structure. Finally, the possible causes of the diseases are discussed.<br>
収録刊行物
-
- 薬学雑誌
-
薬学雑誌 133 (5), 509-517, 2013-05-01
公益社団法人 日本薬学会
- Tweet
詳細情報 詳細情報について
-
- CRID
- 1390282681105841152
-
- NII論文ID
- 130003361944
-
- NII書誌ID
- AN00284903
-
- COI
- 1:STN:280:DC%2BC3snhsVKgtA%3D%3D
-
- ISSN
- 13475231
- 00316903
-
- NDL書誌ID
- 024650602
-
- PubMed
- 23649392
-
- 本文言語コード
- ja
-
- データソース種別
-
- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
-
- 抄録ライセンスフラグ
- 使用不可