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| | <StructureSection load='2xsg' size='340' side='right'caption='[[2xsg]], [[Resolution|resolution]] 2.00Å' scene=''> | | <StructureSection load='2xsg' size='340' side='right'caption='[[2xsg]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2xsg]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/"arthrobacter_luteus"_kaneko_et_al._1969 "arthrobacter luteus" kaneko et al. 1969]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2XSG OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=2XSG FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2xsg]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Cellulosimicrobium_cellulans Cellulosimicrobium cellulans]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2XSG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2XSG FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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=GOL:GLYCEROL'>GOL</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2Å</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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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=GOL:GLYCEROL'>GOL</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=2xsg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xsg OCA], [http://pdbe.org/2xsg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2xsg RCSB], [http://www.ebi.ac.uk/pdbsum/2xsg PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2xsg ProSAT]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2xsg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xsg OCA], [https://pdbe.org/2xsg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2xsg RCSB], [https://www.ebi.ac.uk/pdbsum/2xsg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2xsg ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Arthrobacter luteus kaneko et al. 1969]] | + | [[Category: Cellulosimicrobium cellulans]] |
| - | [[Category: Alpha-mannosidase]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Baranova, E]] | + | [[Category: Baranova E]] |
| - | [[Category: Remaut, H]] | + | [[Category: Remaut H]] |
| - | [[Category: Tiels, P]] | + | [[Category: Tiels P]] |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Mannosidase]]
| + | |
| Structural highlights
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ 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. A bacterial glycosidase enables mannose-6-phosphate modification and improved cellular uptake of yeast-produced recombinant human lysosomal enzymes. Nat Biotechnol. 2012 Dec;30(12):1225-31. doi: 10.1038/nbt.2427. Epub 2012 Nov 18. PMID:23159880 doi:http://dx.doi.org/10.1038/nbt.2427
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