7p32
From Proteopedia
(Difference between revisions)
(New page: '''Unreleased structure''' The entry 7p32 is ON HOLD Authors: Roig-Zamboni, V., Kok, K., Overkleeft, H., Artola, M., Sulzenbacher, G. Description: Crystal structure of human lysosomal ...) |
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of human lysosomal acid-alpha-glucosidase, GAA, in complex with cyclosulfamidate 6== | |
| + | <StructureSection load='7p32' size='340' side='right'caption='[[7p32]], [[Resolution|resolution]] 1.82Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[7p32]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7P32 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7P32 FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.82Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=56I:[(1R,2R,3R,4R,5S)-2-(hydroxymethyl)-3,4,5-tris(oxidanyl)cyclohexyl]sulfamic+acid'>56I</scene>, <scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=CSO:S-HYDROXYCYSTEINE'>CSO</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=7p32 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7p32 OCA], [https://pdbe.org/7p32 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7p32 RCSB], [https://www.ebi.ac.uk/pdbsum/7p32 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7p32 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
| + | [https://www.uniprot.org/uniprot/LYAG_HUMAN LYAG_HUMAN] Glycogen storage disease due to acid maltase deficiency, infantile onset;Glycogen storage disease due to acid maltase deficiency, juvenile onset;Glycogen storage disease due to acid maltase deficiency, adult onset. The disease is caused by mutations affecting the gene represented in this entry. | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/LYAG_HUMAN LYAG_HUMAN] Essential for the degradation of glygogen to glucose in lysosomes. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | alpha-Glucosidase inhibitors are potential therapeutics for the treatment of diabetes, viral infections, and Pompe disease. Herein, we report a 1,6-epi-cyclophellitol cyclosulfamidate as a new class of reversible alpha-glucosidase inhibitors that displays enzyme inhibitory activity by virtue of its conformational mimicry of the substrate when bound in the Michaelis complex. The alpha-d-glc-configured cyclophellitol cyclosulfamidate 4 binds in a competitive manner the human lysosomal acid alpha-glucosidase (GAA), ER alpha-glucosidases, and, at higher concentrations, intestinal alpha-glucosidases, displaying an excellent selectivity over the human beta-glucosidases GBA and GBA2 and glucosylceramide synthase (GCS). Cyclosulfamidate 4 stabilizes recombinant human GAA (rhGAA, alglucosidase alfa, Myozyme) in cell medium and plasma and facilitates enzyme trafficking to lysosomes. It stabilizes rhGAA more effectively than existing small-molecule chaperones and does so in vitro, in cellulo, and in vivo in zebrafish, thus representing a promising therapeutic alternative to Miglustat for Pompe disease. | ||
| - | + | 1,6-epi-Cyclophellitol Cyclosulfamidate Is a Bona Fide Lysosomal alpha-Glucosidase Stabilizer for the Treatment of Pompe Disease.,Kok K, Kuo CL, Katzy RE, Lelieveld LT, Wu L, Roig-Zamboni V, van der Marel GA, Codee JDC, Sulzenbacher G, Davies GJ, Overkleeft HS, Aerts JMFG, Artola M J Am Chem Soc. 2022 Aug 17;144(32):14819-14827. doi: 10.1021/jacs.2c05666. Epub , 2022 Aug 2. PMID:35917590<ref>PMID:35917590</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: | + | <div class="pdbe-citations 7p32" style="background-color:#fffaf0;"></div> |
| - | [[Category: | + | |
| - | [[Category: | + | ==See Also== |
| - | [[Category: Roig-Zamboni | + | *[[Alpha-glucosidase 3D structures|Alpha-glucosidase 3D structures]] |
| - | [[Category: | + | == References == |
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Artola M]] | ||
| + | [[Category: Kok K]] | ||
| + | [[Category: Overkleeft H]] | ||
| + | [[Category: Roig-Zamboni V]] | ||
| + | [[Category: Sulzenbacher G]] | ||
Current revision
Crystal structure of human lysosomal acid-alpha-glucosidase, GAA, in complex with cyclosulfamidate 6
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