Structural highlights
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 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. References
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