5nn3: Difference between revisions
New page: '''Unreleased structure''' The entry 5nn3 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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The entry | ==Crystal structure of human lysosomal acid-alpha-glucosidase, GAA== | ||
<StructureSection load='5nn3' size='340' side='right'caption='[[5nn3]], [[Resolution|resolution]] 1.90Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5nn3]] 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=5NN3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5NN3 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]] 1.9Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</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=5nn3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5nn3 OCA], [https://pdbe.org/5nn3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5nn3 RCSB], [https://www.ebi.ac.uk/pdbsum/5nn3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5nn3 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 5nn3" 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]] | |||
Latest revision as of 16:10, 15 November 2023
Crystal structure of human lysosomal acid-alpha-glucosidase, GAACrystal structure of human lysosomal acid-alpha-glucosidase, GAA
Structural highlights
DiseaseLYAG_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. FunctionLYAG_HUMAN Essential for the degradation of glygogen to glucose in lysosomes. Publication Abstract from PubMedPompe 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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