| Autor: |
Zamboni, Véronique Roig-, Cobucci-Ponzano, Beatrice, Iacono, Roberta, Ferrara, Maria Carmina, Germany, Stanley, Bourne, Yves, Parenti, Giancarlo, Moracci, Marco, Sulzenbacher, Gerlind |
| Zdroj: |
Nature Communications; 10/24/2017, Vol. 8 Issue 1, p1-10, 10p, 4 Diagrams, 1 Chart |
| Abstrakt: |
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. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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