TRNA guanine transglycosylase

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.

The enzyme tRNA-guanine transglycosylase (TGT) catalyzes the complete exchange of a base in tRNA [25, 26]. Upon reaction, guanine in the wobble position of tRNAs with the anticodon sequence GUN is replaced by the modified bases... 

Romier, C., Ficner, R., Suck, D. Structural basis of base exchange by tRNA guanine transglycosylase. In Modification and Editing of RNA, ASM Press, Washington, DC, 1998, pp. 169-182. 

Durand, J.M., Okada, N., Tobe, T., Watar-ai, M., Fukuda, I., Suzuki, T., Nakata, N., Komatsu, K., Yoshikawa, M., Sasakawa, C. vacC, a virulence-associated chromosomal locus of Shigella flexneri, is homologous to tgt, a gene encoding tRNA—guanine transglycosylase (TGT) of Escherichia coli K-12. J. Bacteriol. 1994, 176, 4627-4634. 

Romier, C., Meyer, J.E., Suck, D. Slight sequence variations of a common fold explain the substrate specificities of tRNA-guanine transglycosylases from the three kingdoms. FEBS Lett. 1997, 416, 93-98. 

Brenk, R., Stubbs, M.T., Heine, A., Reuter, K., Klebe, G. Flexible adaptations in the structure of the tRNA modifying enzyme tRNA-guanine transglycosylase and their implications for substrate selectivity, reaction mechanism and structure-based drug design. ChemBiochem 2003, 4, 1066-1077. 

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. 

Zymomonas mobilis tRNA guanine transglycosylase IPOB Cys 1 CySba 2 CySa 25 HiSa... 

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. 

Stengl, B., Reuter, K., and Klebe, G. (2005) Mechanism and substrate specificity of tRNA-guanine transglycosylases (TGTs) tRNA-modifying enzymes from the... 

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