| Structural highlights
7p2z is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , , , , , , , , |
| NonStd Res: | |
| 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
alpha-Glucosidase inhibitors are potential therapeutics for the treatment of diabetes, viral infections, and Pompe disease. Herein, we report a 1,6-epi-cyclophellitol cyclosulfamidate as a new class of reversible alpha-glucosidase inhibitors that displays enzyme inhibitory activity by virtue of its conformational mimicry of the substrate when bound in the Michaelis complex. The alpha-d-glc-configured cyclophellitol cyclosulfamidate 4 binds in a competitive manner the human lysosomal acid alpha-glucosidase (GAA), ER alpha-glucosidases, and, at higher concentrations, intestinal alpha-glucosidases, displaying an excellent selectivity over the human beta-glucosidases GBA and GBA2 and glucosylceramide synthase (GCS). Cyclosulfamidate 4 stabilizes recombinant human GAA (rhGAA, alglucosidase alfa, Myozyme) in cell medium and plasma and facilitates enzyme trafficking to lysosomes. It stabilizes rhGAA more effectively than existing small-molecule chaperones and does so in vitro, in cellulo, and in vivo in zebrafish, thus representing a promising therapeutic alternative to Miglustat for Pompe disease.
1,6-epi-Cyclophellitol Cyclosulfamidate Is a Bona Fide Lysosomal alpha-Glucosidase Stabilizer for the Treatment of Pompe Disease.,Kok K, Kuo CL, Katzy RE, Lelieveld LT, Wu L, Roig-Zamboni V, van der Marel GA, Codee JDC, Sulzenbacher G, Davies GJ, Overkleeft HS, Aerts JMFG, Artola M J Am Chem Soc. 2022 Aug 17;144(32):14819-14827. doi: 10.1021/jacs.2c05666. Epub, 2022 Aug 2. PMID:35917590[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Kok K, Kuo CL, Katzy RE, Lelieveld LT, Wu L, Roig-Zamboni V, van der Marel GA, Codee JDC, Sulzenbacher G, Davies GJ, Overkleeft HS, Aerts JMFG, Artola M. 1,6-epi-Cyclophellitol Cyclosulfamidate Is a Bona Fide Lysosomal alpha-Glucosidase Stabilizer for the Treatment of Pompe Disease. J Am Chem Soc. 2022 Aug 17;144(32):14819-14827. doi: 10.1021/jacs.2c05666. Epub, 2022 Aug 2. PMID:35917590 doi:http://dx.doi.org/10.1021/jacs.2c05666
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