3CZS

Golgi alpha-mannosidase II (D204A nucleophile mutant)

Summary for 3CZS

• Entry DOI: 10.2210/pdb3czs/pdb
• Related: 1HTY 1HWW 1HXK 1PS2 1QWN 1QWU 1QX1 1R33 1R34 2ALW 2F7O 2F7P 2F7Q 2F7R 3BUB 3BUD 3BUI 3BUP 3BUQ 3BVT 3BVU 3BVV 3BVW 3BVX 3CV5 3CZN 3D4Y 3D4Z 3D50 3D51 3D52
• Descriptor: Alpha-mannosidase 2, 2-acetamido-2-deoxy-beta-D-glucopyranose, alpha-D-mannopyranose, ... (6 entities in total)
• Functional Keywords: hydrolase, glycosyl hydrolase, mannosidase, n-terminal alpha-beta domain, three helix bundle, 2 c-terminal beta barrels
• Biological source: Drosophila melanogaster (fruit fly)
• Total number of polymer chains: 1
• Total formula weight: 120242.55

Authors

Shah, N.,Rose, D.R. (deposition date: 2008-04-29, release date: 2008-06-24, Last modification date: 2024-10-09)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.3 Å)