5NN6

Crystal structure of human lysosomal acid-alpha-glucosidase, GAA, in complex with N-hydroxyethyl-1-deoxynojirimycin

Summary for 5NN6

• Entry DOI: 10.2210/pdb5nn6/pdb
• Related: 5NN3 5NN4 5NN5
• Descriptor: Lysosomal alpha-glucosidase, TRIETHYLENE GLYCOL, GLYCEROL, ... (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: 101829.62

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

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: 29061980
DOI: 10.1038/s41467-017-01263-3

Experimental method

X-RAY DIFFRACTION (2 Å)