7p4c

Crystal Structure of Agd31B, alpha-transglucosylase in Glycoside Hydrolase Family 31, in complex with noncovalent Cyclophellitol Sulfamidate probe KK131

spinqualitylabelsall models 7p4c, resolution 1.86Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7p4c is a 1 chain structure with sequence from Cellvibrio japonicus Ueda107. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.86Å Ligands: 5OV, EDO, OXL, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function OL4AG_CELJU Alpha-transglucosylase that specifically transfers single glucosyl units from alpha(1->4)-glucans to the non-reducing terminal 4-OH of glucose and alpha(1->4)- and alpha(1->6)-linked glucosyl residues. Acts on amylose, amylopectin, glycogen and maltooligosaccharides, with the highest activity with maltotriose as a donor, and also accepts maltose. Does not act as a hydrolase: weak hydrolysis activity is only observed on the disaccharide maltose. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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