1KRF

STRUCTURE OF P. CITRINUM ALPHA 1,2-MANNOSIDASE REVEALS THE BASIS FOR DIFFERENCES IN SPECIFICITY OF THE ER AND GOLGI CLASS I ENZYMES

1KRF の概要

• エントリーDOI: 10.2210/pdb1krf/pdb
• 関連するPDBエントリー: 1KKT 1KRE
• 分子名称: Mannosyl-oligosaccharide alpha-1,2-mannosidase, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]alpha-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total)
• 機能のキーワード: (alpha/alpha)7-barrel, hydrolase
• 由来する生物種: Penicillium citrinum
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 117316.93

構造登録者

Lobsanov, Y.D.,Vallee, F.,Imberty, A.,Yoshida, T.,Yip, P.,Herscovics, A.,Howell, P.L. (登録日: 2002-01-09, 公開日: 2002-02-20, 最終更新日: 2024-11-06)

主引用文献

Lobsanov, Y.D.,Vallee, F.,Imberty, A.,Yoshida, T.,Yip, P.,Herscovics, A.,Howell, P.L.
Structure of Penicillium citrinum alpha 1,2-mannosidase reveals the basis for differences in specificity of the endoplasmic reticulum and Golgi class I enzymes.
J.Biol.Chem., 277:5620-5630, 2002

PubMed Abstract: Class I alpha1,2-mannosidases (glycosylhydrolase family 47) are key enzymes in the maturation of N-glycans. This protein family includes two distinct enzymatically active subgroups. Subgroup 1 includes the yeast and human endoplasmic reticulum (ER) alpha1,2-mannosidases that primarily trim Man(9)GlcNAc(2) to Man(8)GlcNAc(2) isomer B whereas subgroup 2 includes mammalian Golgi alpha1,2-mannosidases IA, IB, and IC that trim Man(9)GlcNAc(2) to Man(5)GlcNAc(2) via Man(8)GlcNAc(2) isomers A and C. The structure of the catalytic domain of the subgroup 2 alpha1,2-mannosidase from Penicillium citrinum has been determined by molecular replacement at 2.2-A resolution. The fungal alpha1,2-mannosidase is an (alphaalpha)(7)-helix barrel, very similar to the subgroup 1 yeast (Vallée, F., Lipari, F., Yip, P., Sleno, B., Herscovics, A., and Howell, P. L. (2000) EMBO J. 19, 581-588) and human (Vallée, F., Karaveg, K., Herscovics, A., Moremen, K. W., and Howell, P. L. (2000) J. Biol. Chem. 275, 41287-41298) ER enzymes. The location of the conserved acidic residues of the catalytic site and the binding of the inhibitors, kifunensine and 1-deoxymannojirimycin, to the essential calcium ion are conserved in the fungal enzyme. However, there are major structural differences in the oligosaccharide binding site between the two alpha1,2-mannosidase subgroups. In the subgroup 1 enzymes, an arginine residue plays a critical role in stabilizing the oligosaccharide substrate. In the fungal alpha1,2-mannosidase this arginine is replaced by glycine. This replacement and other sequence variations result in a more spacious carbohydrate binding site. Modeling studies of interactions between the yeast, human and fungal enzymes with different Man(8)GlcNAc(2) isomers indicate that there is a greater degree of freedom to bind the oligosaccharide in the active site of the fungal enzyme than in the yeast and human ER alpha1,2-mannosidases.

PubMed: 11714724
DOI: 10.1074/jbc.M110243200

実験手法

X-RAY DIFFRACTION (2.2 Å)