10OI
Structure of Clostridium difficile Toxin B (TcdB) glucosyltransferase in complex with UDP linked isofagomine analog 3-5
This is a non-PDB format compatible entry.
Summary for 10OI
| Entry DOI | 10.2210/pdb10oi/pdb |
| Related | 7LOU 7LOV |
| Descriptor | Toxin B, URIDINE-5'-DIPHOSPHATE, 1-(5-O-{3-[(3R,4R,5R)-3,4-dihydroxy-5-(hydroxymethyl)piperidin-1-yl]propyl}-alpha-L-lyxofuranosyl)pyrimidine-2,4(1H,3H)-dione, ... (6 entities in total) |
| Functional Keywords | inhibitor, complex, transferase |
| Biological source | Clostridioides difficile |
| Total number of polymer chains | 2 |
| Total formula weight | 130685.03 |
| Authors | Paparella, A.S.,Gilaj, N.,Wagner, A.G.,Schramm, V.L.,Ghosh, A. (deposition date: 2026-01-29, release date: 2026-07-08) |
| Primary citation | Shaffer, K.J.,Gilaj, N.,Wagner, A.G.,Popadynec, M.,Groom, D.P.,Hughes, L.A.,Ghosh, A.,Paparella, A.,Tyler, P.C.,Lamiable-Oulaidi, F.,Schramm, V.L. Isofagomine Derivatives as TcdB Glucosyltransferase Inhibitors. J.Med.Chem., 2026 Cited by PubMed Abstract: () is the leading cause of hospital-acquired life-threatening diarrhea. toxins TcdA and TcdB contain a glucosyltransferase domain (GTD) that glucosylates and inactivates host GTPases, disrupting the actin cytoskeleton and compromising epithelial integrity. TcdB, the most potent virulence factor, drives disease progression and is a high-priority target fortreatment and prevention. The iminosugar isofagomine has been shown to inhibit the GTD activity of TcdB by an uncompetitive inhibition mechanism, but requires the uridine 5'-diphosphate (UDP) reaction product. Compound classes synthesized here, ranging from isofagomine analogues to acyclic mimics, probe which modifications can tap into UDP-binding energy to enhance inhibition. Structure-activity relationship studies of isofagomine derivatives demonstrate remarkable specificity for isofagomine and limited advantage in accessing the UDP-binding site. Fluorescence and absorbance assays allowed facile inhibition assessment of TcdB's UDP-glucose hydrolysis. The molecules reported here guide scaffolds for future catalytic site inhibitors. PubMed: 42383693DOI: 10.1021/acs.jmedchem.6c00369 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.65 Å) |
Structure validation
Download full validation report
