1kkt
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Structure of P. citrinum alpha 1,2-mannosidase reveals the basis for differences in specificity of the ER and Golgi Class I enzymes
OverviewOverview
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, (Vallee, F., Lipari, F., Yip, P., Sleno, B., Herscovics, A., and Howell, P. L. (2000) EMBO J. 19, 581-588) and human (Vallee, 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.
About this StructureAbout this Structure
1KKT is a Single protein structure of sequence from Penicillium citrinum with CA as ligand. Active as Mannosyl-oligosaccharide 1,2-alpha-mannosidase, with EC number 3.2.1.113 Full crystallographic information is available from OCA.
ReferenceReference
Structure of Penicillium citrinum alpha 1,2-mannosidase reveals the basis for differences in specificity of the endoplasmic reticulum and Golgi class I enzymes., Lobsanov YD, Vallee F, Imberty A, Yoshida T, Yip P, Herscovics A, Howell PL, J Biol Chem. 2002 Feb 15;277(7):5620-30. Epub 2001 Nov 19. PMID:11714724
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