5NPD
Crystal Structure of D412N nucleophile mutant cjAgd31B (alpha-transglucosylase from Glycoside Hydrolase Family 31) in complex with alpha Cyclophellitol Aziridine probe CF021
Summary for 5NPD
| Entry DOI | 10.2210/pdb5npd/pdb |
| Related | 5NPB |
| Descriptor | Oligosaccharide 4-alpha-D-glucosyltransferase, SULFATE ION, TETRAETHYLENE GLYCOL, ... (7 entities in total) |
| Functional Keywords | hydrolase |
| Biological source | Cellvibrio japonicus |
| Total number of polymer chains | 1 |
| Total formula weight | 95962.80 |
| Authors | Wu, L.,Davies, G.J. (deposition date: 2017-04-16, release date: 2017-08-09, Last modification date: 2024-10-23) |
| Primary citation | Artola, M.,Wu, L.,Ferraz, M.J.,Kuo, C.L.,Raich, L.,Breen, I.Z.,Offen, W.A.,Codee, J.D.C.,van der Marel, G.A.,Rovira, C.,Aerts, J.M.F.G.,Davies, G.J.,Overkleeft, H.S. 1,6-Cyclophellitol Cyclosulfates: A New Class of Irreversible Glycosidase Inhibitor. ACS Cent Sci, 3:784-793, 2017 Cited by PubMed Abstract: The essential biological roles played by glycosidases, coupled to the diverse therapeutic benefits of pharmacologically targeting these enzymes, provide considerable motivation for the development of new inhibitor classes. Cyclophellitol epoxides and aziridines are recently established covalent glycosidase inactivators. Inspired by the application of cyclic sulfates as electrophilic equivalents of epoxides in organic synthesis, we sought to test whether cyclophellitol cyclosulfates would similarly act as irreversible glycosidase inhibitors. Here we present the synthesis, conformational analysis, and application of novel 1,6-cyclophellitol cyclosulfates. We show that 1,6--cyclophellitol cyclosulfate (α-cyclosulfate) is a rapidly reacting α-glucosidase inhibitor whose C chair conformation matches that adopted by α-glucosidase Michaelis complexes. The 1,6-cyclophellitol cyclosulfate (β-cyclosulfate) reacts more slowly, likely reflecting its conformational restrictions. Selective glycosidase inhibitors are invaluable as mechanistic probes and therapeutic agents, and we propose cyclophellitol cyclosulfates as a valuable new class of carbohydrate mimetics for application in these directions. PubMed: 28776021DOI: 10.1021/acscentsci.7b00214 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.95 Å) |
Structure validation
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