4aq0
From Proteopedia
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| - | [[ | + | ==Structure of the Gh92 Family Glycosyl Hydrolase Ccman5 in complex with deoxymannojirimycin== |
| + | <StructureSection load='4aq0' size='340' side='right' caption='[[4aq0]], [[Resolution|resolution]] 2.09Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[4aq0]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Cellulosimicrobium_cellulans Cellulosimicrobium cellulans]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4AQ0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4AQ0 FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=B3P:2-[3-(2-HYDROXY-1,1-DIHYDROXYMETHYL-ETHYLAMINO)-PROPYLAMINO]-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>B3P</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=DMJ:1-DEOXYMANNOJIRIMYCIN'>DMJ</scene></td></tr> | ||
| + | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Alpha-mannosidase Alpha-mannosidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.24 3.2.1.24] </span></td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4aq0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4aq0 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4aq0 RCSB], [http://www.ebi.ac.uk/pdbsum/4aq0 PDBsum]</span></td></tr> | ||
| + | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Lysosomal storage diseases are treated with human lysosomal enzymes produced in mammalian cells. Such enzyme therapeutics contain relatively low levels of mannose-6-phosphate, which is required to target them to the lysosomes of patient cells. Here we describe a method for increasing mannose-6-phosphate modification of lysosomal enzymes produced in yeast. We identified a glycosidase from C. cellulans that 'uncaps' N-glycans modified by yeast-type mannose-Pi-6-mannose to generate mammalian-type N-glycans with a mannose-6-phosphate substitution. Determination of the crystal structure of this glycosidase provided insight into its substrate specificity. We used this uncapping enzyme together with alpha-mannosidase to produce in yeast a form of the Pompe disease enzyme alpha-glucosidase rich in mannose-6-phosphate. Compared with the currently used therapeutic version, this form of alpha-glucosidase was more efficiently taken up by fibroblasts from Pompe disease patients, and it more effectively reduced cardiac muscular glycogen storage in a mouse model of the disease. | ||
| - | + | A bacterial glycosidase enables mannose-6-phosphate modification and improved cellular uptake of yeast-produced recombinant human lysosomal enzymes.,Tiels P, Baranova E, Piens K, De Visscher C, Pynaert G, Nerinckx W, Stout J, Fudalej F, Hulpiau P, Tannler S, Geysens S, Van Hecke A, Valevska A, Vervecken W, Remaut H, Callewaert N Nat Biotechnol. 2012 Dec;30(12):1225-31. doi: 10.1038/nbt.2427. Epub 2012 Nov 18. PMID:23159880<ref>PMID:23159880</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | + | == References == | |
| - | + | <references/> | |
| - | == | + | __TOC__ |
| - | + | </StructureSection> | |
[[Category: Alpha-mannosidase]] | [[Category: Alpha-mannosidase]] | ||
[[Category: Cellulosimicrobium cellulans]] | [[Category: Cellulosimicrobium cellulans]] | ||
| - | [[Category: Baranova, E | + | [[Category: Baranova, E]] |
| - | [[Category: Callewaert, N | + | [[Category: Callewaert, N]] |
| - | [[Category: Remaut, H | + | [[Category: Remaut, H]] |
| - | [[Category: Tiels, P | + | [[Category: Tiels, P]] |
[[Category: Hydrolase]] | [[Category: Hydrolase]] | ||
[[Category: Mannosidase]] | [[Category: Mannosidase]] | ||
Revision as of 17:36, 9 December 2014
Structure of the Gh92 Family Glycosyl Hydrolase Ccman5 in complex with deoxymannojirimycin
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