5NN4
Crystal structure of human lysosomal acid-alpha-glucosidase, GAA, in complex with N-acetyl-cysteine
Summary for 5NN4
| Entry DOI | 10.2210/pdb5nn4/pdb |
| Related | 5NN3 |
| Descriptor | Lysosomal alpha-glucosidase, GLYCEROL, 1,2-ETHANEDIOL, ... (12 entities in total) |
| Functional Keywords | glycoside hydrolase, lysosome, glycogen catabolism, pompe disease, hydrolase |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 1 |
| Total formula weight | 102096.47 |
| Authors | Roig-Zamboni, V.,Cobucci-Ponzano, B.,Iacono, R.,Ferrara, M.C.,Germany, S.,Parenti, G.,Bourne, Y.,Moracci, M. (deposition date: 2017-04-08, release date: 2017-10-25, Last modification date: 2024-10-16) |
| Primary citation | Roig-Zamboni, V.,Cobucci-Ponzano, B.,Iacono, R.,Ferrara, M.C.,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, 8:1111-1111, 2017 Cited by PubMed Abstract: Pompe disease, a rare lysosomal storage disease caused by deficiency of the lysosomal acid α-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. PubMed: 29061980DOI: 10.1038/s41467-017-01263-3 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.83 Å) |
Structure validation
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