3CV5

GOLGI MANNOSIDASE II D204A catalytic nucleophile mutant complex with 3alpha,6alpha-mannopentaose

3CV5 の概要

• エントリーDOI: 10.2210/pdb3cv5/pdb
• 関連するPDBエントリー: 1HTY 1HWW 1HXK 1PS2 1QWN 1QWU 1QX1 1R33 1R34 2ALW 2F7O 2F7P 2F7Q 2F7R 3BUB 3BUD 3BUI 3BUP 3BUQ 3BVT 3BVU 3BVV 3BVW 3BVX
• 分子名称: Alpha-mannosidase 2, alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]alpha-D-mannopyranose-(1-6)-[alpha-D-mannopyranose-(1-3)]beta-D-mannopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total)
• 機能のキーワード: family 38 glycosyl hydrolase, glycosidase, golgi apparatus, membrane, metal-binding, signal-anchor, transmembrane, hydrolase
• 由来する生物種: Drosophila melanogaster (Fruit fly)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 120891.11

構造登録者

Shah, N.,Kuntz, D.A.,Rose, D.R. (登録日: 2008-04-17, 公開日: 2008-06-24, 最終更新日: 2024-10-30)

主引用文献

Shah, N.,Kuntz, D.A.,Rose, D.R.
Golgi alpha-mannosidase II cleaves two sugars sequentially in the same catalytic site.
Proc.Natl.Acad.Sci.Usa, 105:9570-9575, 2008

PubMed Abstract: Golgi alpha-mannosidase II (GMII) is a key glycosyl hydrolase in the N-linked glycosylation pathway. It catalyzes the removal of two different mannosyl linkages of GlcNAcMan(5)GlcNAc(2), which is the committed step in complex N-glycan synthesis. Inhibition of this enzyme has shown promise in certain cancers in both laboratory and clinical settings. Here we present the high-resolution crystal structure of a nucleophile mutant of Drosophila melanogaster GMII (dGMII) bound to its natural oligosaccharide substrate and an oligosaccharide precursor as well as the structure of the unliganded mutant. These structures allow us to identify three sugar-binding subsites within the larger active site cleft. Our results allow for the formulation of the complete catalytic process of dGMII, which involves a specific order of bond cleavage, and a major substrate rearrangement in the active site. This process is likely conserved for all GMII enzymes-but not in the structurally related lysosomal mannosidase-and will form the basis for the design of specific inhibitors against GMII.

PubMed: 18599462
DOI: 10.1073/pnas.0802206105

実験手法

X-RAY DIFFRACTION (1.6 Å)