1hty
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(New page: 200px<br /><applet load="1hty" size="450" color="white" frame="true" align="right" spinBox="true" caption="1hty, resolution 1.40Å" /> '''GOLGI ALPHA-MANNOSID...)
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Revision as of 14:42, 20 November 2007
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GOLGI ALPHA-MANNOSIDASE II
Overview
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 Structure
1HTY is a Single protein structure of sequence from Drosophila melanogaster with NAG, ZN, TRS and MRD 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.
Reference
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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