1GUV

Structure of human chitotriosidase

1GUV の概要

• エントリーDOI: 10.2210/pdb1guv/pdb
• 関連するPDBエントリー: 1HKI 1HKJ 1HKK 1HKM 1LG1 1LG2
• 分子名称: CHITOTRIOSIDASE, 1,2-ETHANEDIOL (3 entities in total)
• 機能のキーワード: hydrolase, chitin degradation, lectin, glycosidase
• 由来する生物種: HOMO SAPIENS (HUMAN)
• 細胞内の位置: Secreted: Q13231
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 41519.52

構造登録者

Von Moeller, H.,Houston, D.,Boot, R.G.,Aerts, J.M.F.G.,Van Aalten, D.M.F. (登録日: 2002-01-31, 公開日: 2003-03-30, 最終更新日: 2024-11-20)

主引用文献

Fusetti, F.,Von Moeller, H.,Houston, D.,Rozeboom, H.J.,Dijkstra, B.W.,Boot, R.G.,Aerts, J.M.F.G.,Van Aalten, D.M.F.
Structure of Human Chitotriosidase - Implications for Specific Inhibitor Design and Function of Mammalian Chitinase-Like Lectins
J.Biol.Chem., 277:25537-, 2002

PubMed Abstract: Chitin hydrolases have been identified in a variety of organisms ranging from bacteria to eukaryotes. They have been proposed to be possible targets for the design of novel chemotherapeutics against human pathogens such as fungi and protozoan parasites as mammals were not thought to possess chitin-processing enzymes. Recently, a human chitotriosidase was described as a marker for Gaucher disease with plasma levels of the enzyme elevated up to 2 orders of magnitude. The chitotriosidase was shown to be active against colloidal chitin and is inhibited by the family 18 chitinase inhibitor allosamidin. Here, the crystal structure of the human chitotriosidase and complexes with a chitooligosaccharide and allosamidin are described. The structures reveal an elongated active site cleft, compatible with the binding of long chitin polymers, and explain the inactivation of the enzyme through an inherited genetic deficiency. Comparison with YM1 and HCgp-39 shows how the chitinase has evolved into these mammalian lectins by the mutation of key residues in the active site, tuning the substrate binding specificity. The soaking experiments with allosamidin and chitooligosaccharides give insight into ligand binding properties and allow the evaluation of differential binding and design of species-selective chitinase inhibitors.

PubMed: 11960986
DOI: 10.1074/JBC.M201636200

実験手法

X-RAY DIFFRACTION (2.35 Å)