9EWF
Cholera toxin B subunit in complex with fluorinated GM1
This is a non-PDB format compatible entry.
Summary for 9EWF
| Entry DOI | 10.2210/pdb9ewf/pdb |
| Related PRD ID | PRD_002568 |
| Descriptor | Cholera enterotoxin subunit B, 2-deoxy-2-fluoro-beta-D-galactopyranose-(1-3)-2-acetamido-2-deoxy-beta-D-galactopyranose-(1-4)-[N-acetyl-alpha-neuraminic acid-(2-3)]beta-D-galactopyranose, (2R,3S,4S,5R,6R)-6-dodecoxy-5-fluoranyl-2-(hydroxymethyl)oxane-3,4-diol, ... (4 entities in total) |
| Functional Keywords | cholera, gm1, fluorinated, complex, toxin |
| Biological source | Vibrio cholerae |
| Total number of polymer chains | 10 |
| Total formula weight | 118611.07 |
| Authors | |
| Primary citation | Jordan, C.,Hayashi, T.,Lobbert, A.,Fan, J.,Teschers, C.S.,Siebold, K.,Aufiero, M.,Pape, F.,Campbell, E.,Axer, A.,Bussmann, K.,Bergander, K.,Kohnke, J.,Gossert, A.D.,Gilmour, R. Probing the Origin of Affinity in the GM1-Cholera Toxin Complex through Site-Selective Editing with Fluorine. Acs Cent.Sci., 10:1481-1489, 2024 Cited by PubMed Abstract: Carbohydrates regulate an inimitable spectrum of biological functions, yet successfully leveraging this therapeutic avenue continues to be frustrated by low affinities with glycan-specific proteins. A conspicuous exception is the interaction of monosialotetrahexosylganglioside (GM1) with the carbohydrate-recognition domain of cholera toxin from : this is one of the strongest protein-carbohydrate interactions known. To establish the importance of a long-discussed key hydrogen bond between C2 of the terminal galactose of GM1 and the B subunit pentamer of cholera toxin (CTB), the total synthesis of a selectively fluorinated GM1 epitope was conducted in 19 steps. This process of molecular editing (OH → F) strategically deletes the hydrogen bond donor while retaining the localized partial charge of the substituent. Comparison of the binding affinity of F-GM1/CTB with native GM1, the GM1 carbohydrate epitope, and -mononitrophenyl-α-galactoside (MNPG) revealed a trend that fully supports the importance of this key interaction. These NMR data suggest that F-GM1 binds in a closely similar conformation as native GM1. Crystallographic analyses of the complex also confirm that the OH → F bioisosteric exchange at C2 of the terminal galactose induces a ring conformation that eliminates key hydrogen bonds: these interactions are compensated for by inter- and intramolecular fluorine-specific interactions. PubMed: 39220706DOI: 10.1021/acscentsci.4c00622 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.1 Å) |
Structure validation
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