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5nn8
From Proteopedia
(Difference between revisions)
(New page: '''Unreleased structure''' The entry 5nn8 is ON HOLD until Paper Publication Authors: Roig-Zamboni, V., Cobucci-Ponzano, B., Iacono, R., Ferrara, M.C., Germany, S., Parenti, G., Bourne,...) |
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of human lysosomal acid-alpha-glucosidase, GAA, in complex with acarbose== | |
| + | <StructureSection load='5nn8' size='340' side='right'caption='[[5nn8]], [[Resolution|resolution]] 2.45Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5nn8]] 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=5NN8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5NN8 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]] 2.45Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AC1:6-METHYL-5-(4,5,6-TRIHYDROXY-3-HYDROXYMETHYL-CYCLOHEX-2-ENYLAMINO)-TETRAHYDRO-PYRAN-2,3,4-TRIOL'>AC1</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=GLC:ALPHA-D-GLUCOSE'>GLC</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=PRD_900007:alpha-acarbose'>PRD_900007</scene>, <scene name='pdbligand=PRD_900110:acarbose-derived+trisaccharide'>PRD_900110</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=5nn8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5nn8 OCA], [https://pdbe.org/5nn8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5nn8 RCSB], [https://www.ebi.ac.uk/pdbsum/5nn8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5nn8 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 == | ||
| + | Pompe disease, a rare lysosomal storage disease caused by deficiency of the lysosomal acid alpha-glucosidase (GAA), is characterized by glycogen accumulation, triggering severe secondary cellular damage and resulting in progressive motor handicap and premature death. Numerous disease-causing mutations in the gaa gene have been reported, but the structural effects of the pathological variants were unknown. Here we present the high-resolution crystal structures of recombinant human GAA (rhGAA), the standard care of Pompe disease. These structures portray the unbound form of rhGAA and complexes thereof with active site-directed inhibitors, providing insight into substrate recognition and the molecular framework for the rationalization of the deleterious effects of disease-causing mutations. Furthermore, we report the structure of rhGAA in complex with the allosteric pharmacological chaperone N-acetylcysteine, which reveals the stabilizing function of this chaperone at the structural level. | ||
| - | + | Structure of human lysosomal acid alpha-glucosidase-a guide for the treatment of Pompe disease.,Roig-Zamboni V, Cobucci-Ponzano B, Iacono R, Ferrara MC, Germany S, Bourne Y, Parenti G, Moracci M, Sulzenbacher G Nat Commun. 2017 Oct 24;8(1):1111. doi: 10.1038/s41467-017-01263-3. PMID:29061980<ref>PMID:29061980</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: | + | <div class="pdbe-citations 5nn8" style="background-color:#fffaf0;"></div> |
| - | [[Category: | + | |
| - | [[Category: | + | ==See Also== |
| - | [[Category: | + | *[[Alpha-glucosidase 3D structures|Alpha-glucosidase 3D structures]] |
| - | [[Category: | + | == References == |
| - | [[Category: | + | <references/> |
| - | [[Category: | + | __TOC__ |
| - | [[Category: | + | </StructureSection> |
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Bourne Y]] | ||
| + | [[Category: Cobucci-Ponzano B]] | ||
| + | [[Category: Ferrara MC]] | ||
| + | [[Category: Germany S]] | ||
| + | [[Category: Iacono R]] | ||
| + | [[Category: Moracci M]] | ||
| + | [[Category: Parenti G]] | ||
| + | [[Category: Roig-Zamboni V]] | ||
Current revision
Crystal structure of human lysosomal acid-alpha-glucosidase, GAA, in complex with acarbose
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