Structural highlights
5nn3 is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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| Ligands: | , , , , , , , , |
| NonStd Res: | |
| Gene: | GAA (HUMAN) |
| Activity: | Alpha-glucosidase, with EC number 3.2.1.20 |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Disease
[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
[LYAG_HUMAN] Essential for the degradation of glygogen to glucose in lysosomes.
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Roig-Zamboni V, Cobucci-Ponzano B, Iacono R, Ferrara MC, Germany S, Bourne Y, Parenti G, Moracci M, Sulzenbacher G. Structure of human lysosomal acid alpha-glucosidase-a guide for the treatment of Pompe disease. Nat Commun. 2017 Oct 24;8(1):1111. doi: 10.1038/s41467-017-01263-3. PMID:29061980 doi:http://dx.doi.org/10.1038/s41467-017-01263-3
