View source for 5nn8


==Crystal structure of human lysosomal acid-alpha-glucosidase, GAA, in complex with acarbose==
<StructureSection load='5nn8' size='340' side='right' caption='[[5nn8]], [[Resolution|resolution]] 2.45&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5nn8]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5NN8 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACR:ALPHA-ACARBOSE'>ACR</scene>, <scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</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='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CSO:S-HYDROXYCYSTEINE'>CSO</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5nn3|5nn3]], [[5nn4|5nn4]], [[5nn5|5nn5]], [[5nn6|5nn6]]</td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GAA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Alpha-glucosidase Alpha-glucosidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.20 3.2.1.20] </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=5nn8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5nn8 OCA], [http://pdbe.org/5nn8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5nn8 RCSB], [http://www.ebi.ac.uk/pdbsum/5nn8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5nn8 ProSAT]</span></td></tr>
</table>
== Disease ==
[[http://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 ==
[[http://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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5nn8" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Alpha-glucosidase]]
[[Category: Human]]
[[Category: Bourne, Y]]
[[Category: Cobucci-Ponzano, B]]
[[Category: Ferrara, M C]]
[[Category: Germany, S]]
[[Category: Iacono, R]]
[[Category: Moracci, M]]
[[Category: Parenti, G]]
[[Category: Roig-Zamboni, V]]
[[Category: Glycogen catabolism]]
[[Category: Glycoside hydrolase]]
[[Category: Hydrolase]]
[[Category: Lysosome]]
[[Category: Pompe disease]]