1hxk
GOLGI ALPHA-MANNOSIDASE II IN COMPLEX WITH DEOXYMANNOJIRIMICIN
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OverviewOverview
Golgi alpha-mannosidase II, a key enzyme in N-glycan processing, is a target in the development of anti- cancer therapies. The crystal structure of Drosophila Golgi alpha-mannosidase II in the absence and presence of the anti-cancer agent swainsonine and the inhibitor deoxymannojirimycin reveals a novel protein fold with an active site zinc intricately involved both in the substrate specificity of the enzyme and directly in the catalytic mechanism. Identification of a putative GlcNAc binding pocket in the vicinity of the active site cavity provides a model for the binding of the GlcNAcMan(5)GlcNAc(2) substrate and the consecutive hydrolysis of the alpha1,6- and alpha1,3-linked mannose residues. The enzyme-inhibitor interactions observed provide insight into the catalytic mechanism, opening the door to the design of novel inhibitors of alpha-mannosidase II.
About this StructureAbout this Structure
1HXK is a Single protein structure of sequence from Drosophila melanogaster with , , and as ligands. Active as Mannosyl-oligosaccharide 1,3-1,6-alpha-mannosidase, with EC number 3.2.1.114 Full crystallographic information is available from OCA.
ReferenceReference
Structure of Golgi alpha-mannosidase II: a target for inhibition of growth and metastasis of cancer cells., van den Elsen JM, Kuntz DA, Rose DR, EMBO J. 2001 Jun 15;20(12):3008-17. PMID:11406577
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