1QWN

GOLGI ALPHA-MANNOSIDASE II Covalent Intermediate Complex with 5-fluoro-gulosyl-fluoride

Summary for 1QWN

• Entry DOI: 10.2210/pdb1qwn/pdb
• Related: 1HTY 1HWW 1HXK 1PS3 1QWU 1QX1
• Descriptor: Alpha-mannosidase II, 2-acetamido-2-deoxy-beta-D-glucopyranose, ZINC ION, ... (7 entities in total)
• Functional Keywords: n-terminal alpha-beta domain, three helix bundle, 2 c-terminal beta barrels, family 38 glycosyl hydrolase, hydrolase
• Biological source: Drosophila melanogaster (fruit fly)
• Total number of polymer chains: 1
• Total formula weight: 120428.69

Authors

Numao, S.,Kuntz, D.A.,Withers, S.G.,Rose, D.R. (deposition date: 2003-09-02, release date: 2003-10-07, Last modification date: 2023-08-16)

Primary citation

Numao, S.,Kuntz, D.A.,Withers, S.G.,Rose, D.R.
Insights into the mechanism of Drosophila melanogaster Golgi alpha-mannosidase II through the structural analysis of covalent reaction intermediates.
J.Biol.Chem., 278:48074-48083, 2003

PubMed Abstract: The family 38 golgi alpha-mannosidase II, thought to cleave mannosidic bonds through a double displacement mechanism involving a reaction intermediate, is a clinically important enzyme involved in glycoprotein processing. The structure of three different covalent glycosyl-enzyme intermediates have been determined to 1.2-A resolution for the Golgi alpha-mannosidase II from Drosophila melanogaster by use of fluorinated sugar analogues, both with the wild-type enzyme and a mutant enzyme in which the acid/base catalyst has been removed. All these structures reveal sugar intermediates bound in a distorted 1S5 skew boat conformation. The similarity of this conformation with that of the substrate in the recently determined structure of the Michaelis complex of a beta-mannanase (Ducros, V. M. A., Zechel, D. L., Murshudov, G. N., Gilbert, H. J., Szabo, L., Stoll, D., Withers, S. G., and Davies, G. J. (2002) Angew. Chem. Int. Ed. Engl. 41, 2824-2827) suggests that these disparate enzymes have recruited common stereoelectronic features in evolving their catalytic mechanisms.

PubMed: 12960159
DOI: 10.1074/jbc.M309249200

Experimental method

X-RAY DIFFRACTION (1.2 Å)