7P4C
Crystal Structure of Agd31B, alpha-transglucosylase in Glycoside Hydrolase Family 31, in complex with noncovalent Cyclophellitol Sulfamidate probe KK131
This is a non-PDB format compatible entry.
Summary for 7P4C
| Entry DOI | 10.2210/pdb7p4c/pdb |
| Related | 7P2Z 7P32 7P4D |
| Descriptor | Oligosaccharide 4-alpha-D-glucosyltransferase, 1,2-ETHANEDIOL, OXALATE ION, ... (6 entities in total) |
| Functional Keywords | glycoside hydrolase, gh31, inhibitor, carbohydrate, hydrolase |
| Biological source | Cellvibrio japonicus (strain Ueda107) (Pseudomonas fluorescens subsp. cellulosa) |
| Total number of polymer chains | 1 |
| Total formula weight | 96048.81 |
| Authors | Wu, L.,Davies, G.J. (deposition date: 2021-07-11, release date: 2022-07-27, Last modification date: 2024-11-13) |
| Primary citation | Kok, K.,Kuo, C.L.,Katzy, R.E.,Lelieveld, L.T.,Wu, L.,Roig-Zamboni, V.,van der Marel, G.A.,Codee, J.D.C.,Sulzenbacher, G.,Davies, G.J.,Overkleeft, H.S.,Aerts, J.M.F.G.,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., 144:14819-14827, 2022 Cited by PubMed Abstract: α-Glucosidase inhibitors are potential therapeutics for the treatment of diabetes, viral infections, and Pompe disease. Herein, we report a 1,6--cyclophellitol cyclosulfamidate as a new class of reversible α-glucosidase inhibitors that displays enzyme inhibitory activity by virtue of its conformational mimicry of the substrate when bound in the Michaelis complex. The α-d-configured cyclophellitol cyclosulfamidate binds in a competitive manner the human lysosomal acid α-glucosidase (GAA), ER α-glucosidases, and, at higher concentrations, intestinal α-glucosidases, displaying an excellent selectivity over the human β-glucosidases GBA and GBA2 and glucosylceramide synthase (GCS). Cyclosulfamidate 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 , , and in zebrafish, thus representing a promising therapeutic alternative to Miglustat for Pompe disease. PubMed: 35917590DOI: 10.1021/jacs.2c05666 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.86 Å) |
Structure validation
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