TRNA guanine transglycosylase inhibitors

Brenk R, Meyer EA, Reuter K, Stubbs MT, Garcia GA, Diederich E, Klebe G. Crystallographic study of inhibitors of tRNA-guanine transglycosylase snggests a new structure-based pharmacophore for virtual screening. J Mol Biol 2004 338 55-75. 

Fig. 4.6 Example for successful structure-based virtual screening to identify submicromolar tRNA-guanine transglycosylase (TGT) inhibitors based on X-ray structures ofweaker ligands.

J.D., Garcia, G.A., Reuter, K., Klebe, G. From hit to lead de novo design based on virtual screening hits of inhibitors of tRNA-guanine transglycosylase, a putative target of shigellosis therapy. Helv. Chim. Acta 2003, 86, 1435-1452. 

Meyer, E.A., Brenk, R., Castellano, R.K., Furler, M., Klebe, G., Dietrich F. De novo design, synthesis and in vitro evaluation of inhibitors for prokaryotic tRNA-guanine transglycosylase a dramatic sulfur effect on binding affinity. ChemBiochem 2002, 3, 250-253. 

Stengl, B., Meyer, E.A., Heine, A., Brenk, R., Diederich, F., and Klebe, G. (2007) Crystal structures of tRNA-guanine transglycosylase (TGI) in complex with novel and potent inhibitors umavel pronounced induced-fit adaptations and suggest dimer formation upon substrate binding, /oumai of Molecular Biology, 370, 492-511. 

Figure 12.6 Example for successful structure-based virtual screening to identify submicromolar tRNA-guanine transglycosylase (TGT) inhibitors based on X-ray structures of weaker ligands, (a) X-ray structure of Zymomonas mobilis TGT at 2.1 A resolution (PDB entry 1N2V). (b) Experimental binding mode for pyridazinedione scaffold (K 83 pM) including structural water molecules from 1N2V. (c) Definition of structure-based pharmacophore model with ligand interactions...

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