6FPU
tRNA guanine Transglycosylase (TGT) in co-crystallized complex with 6-amino-2-((((3aS,5aR,8bS)-2,2,7,7-tetramethyltetrahydro-3aH-bis([1,3]dioxolo)[4,5-b:4',5'-d]pyran-3a-yl)methyl)amino)-1,7-dihydro-8H-imidazo[4,5-g]quinazolin-8-one
Summary for 6FPU
| Entry DOI | 10.2210/pdb6fpu/pdb |
| Related | 5JSV 5JSW |
| Descriptor | Queuine tRNA-ribosyltransferase, ZINC ION, GLYCEROL, ... (6 entities in total) |
| Functional Keywords | co-crystallization, transferase, transferase inhibitor |
| Biological source | Zymomonas mobilis subsp. mobilis (strain ATCC 31821 / ZM4 / CP4) |
| Total number of polymer chains | 1 |
| Total formula weight | 43669.22 |
| Authors | Nguyen, A.,Heine, A.,Klebe, G. (deposition date: 2018-02-12, release date: 2019-03-13, Last modification date: 2024-01-17) |
| Primary citation | Movsisyan, L.D.,Schafer, E.,Nguyen, A.,Ehrmann, F.R.,Schwab, A.,Rossolini, T.,Zimmerli, D.,Wagner, B.,Daff, H.,Heine, A.,Klebe, G.,Diederich, F. Sugar Acetonides are a Superior Motif for Addressing the Large, Solvent-Exposed Ribose-33 Pocket of tRNA-Guanine Transglycosylase. Chemistry, 24:9957-9967, 2018 Cited by PubMed Abstract: The intestinal disease shigellosis caused by Shigella bacteria affects over 120 million people annually. There is an urgent demand for new drugs as resistance against common antibiotics emerges. Bacterial tRNA-guanine transglycosylase (TGT) is a druggable target and controls the pathogenicity of Shigella flexneri. We report the synthesis of sugar-functionalized lin-benzoguanines addressing the ribose-33 pocket of TGT from Zymomonas mobilis. Ligand binding was analyzed by isothermal titration calorimetry and X-ray crystallography. Pocket occupancy was optimized by variation of size and protective groups of the sugars. The participation of a polycyclic water-cluster in the recognition of the sugar moiety was revealed. Acetonide-protected ribo- and psicofuranosyl derivatives are highly potent, benefiting from structural rigidity, good solubility, and metabolic stability. We conclude that sugar acetonides have a significant but not yet broadly recognized value in drug development. PubMed: 29939431DOI: 10.1002/chem.201801756 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.36 Å) |
Structure validation
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