4GI4
tRNA Guanine Transglycosylase in complex with disubstituted lin-benzoguanine inhibitor
Summary for 4GI4
| Entry DOI | 10.2210/pdb4gi4/pdb |
| Related | 3GC4 4GG9 4GH1 4GH3 |
| Descriptor | Queuine tRNA-ribosyltransferase, 6-amino-4-[2-(benzylamino)ethyl]-2-[(2-phenylethyl)amino]-1,7-dihydro-8H-imidazo[4,5-g]quinazolin-8-one, ZINC ION, ... (4 entities in total) |
| Functional Keywords | tim barrel glycosyltransferase, queuosine, biosynthesis, trna processing, trna, transferase-transferase inhibitor complex, transferase/transferase inhibitor |
| Biological source | Zymomonas mobilis subsp. mobilis |
| Total number of polymer chains | 1 |
| Total formula weight | 43444.65 |
| Authors | Immekus, F.,Klebe, G. (deposition date: 2012-08-08, release date: 2013-09-04, Last modification date: 2025-11-12) |
| Primary citation | Barandun, L.J.,Immekus, F.,Kohler, P.C.,Ritschel, T.,Heine, A.,Orlando, P.,Klebe, G.,Diederich, F. High-affinity inhibitors of Zymomonas mobilis tRNA-guanine transglycosylase through convergent optimization. Acta Crystallogr.,Sect.D, 69:1798-1807, 2013 Cited by PubMed Abstract: The tRNA-modifying enzyme tRNA-guanine transglycosylase (TGT) has been recognized as a drug target for the treatment of the foodborne illness shigellosis. The active site of TGT consists of three pockets: the central guanine/preQ1 recognition site and the ribose-33 and ribose-34 pockets. In previous work, lin-benzoguanines and lin-benzohypoxanthines, which differ by the presence of an exocyclic NH2 group in the former and its absence in the latter, were used as central scaffolds that bind to the guanine/preQ1 recognition site and allow suitable functionalization along exit vectors targeting the two ribose pockets. The substituents for both of these two pockets have been optimized individually. Here, a series of bifunctionalized inhibitors that occupy both ribose pockets are reported for the first time. Dissociation constants Kd down to the picomolar range were measured for the bifunctionalized lin-benzoguanine-based ligands and Kd values in the nanomolar range were measured for the corresponding lin-benzohypoxanthine-based ligands. The binding mode of all inhibitors was elucidated by X-ray crystal structure analysis. A remarkable influence of the crystallization protocol on the solvation pattern in the solid state and the residual mobility of the bound ligands was observed. PubMed: 23999303DOI: 10.1107/S0907444913014509 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.97 Å) |
Structure validation
Download full validation report
