1n2v
From Proteopedia
Crystal Structure of TGT in complex with 2-Butyl-5,6-dihydro-1H-imidazo[4,5-d]pyridazine-4,7-dione
Overview
Eubacterial tRNA-guanine transglycosylase (TGT) is involved in the hypermodification of cognate tRNAs, leading to the exchange of G34 by preQ1 at the wobble position in the anticodon loop. Mutation of the tgt gene in Shigella flexneri results in a significant loss of pathogenicity of the bacterium due to inefficient translation of a virulence protein mRNA. Herein, we describe the discovery of a ligand with an unexpected binding mode. On the basis of this binding mode, three slightly deviating pharmacophore hypotheses have been derived. Virtual screening based on this composite pharmacophore model retrieved a set of potential TGT inhibitors belonging to several compound classes. All nine tested inhibitors being representatives of these classes showed activity in the micromolar range, two of them even in the submicromolar range.
About this Structure
1N2V is a Single protein structure of sequence from Zymomonas mobilis. Full crystallographic information is available from OCA.
Reference
Virtual screening for submicromolar leads of tRNA-guanine transglycosylase based on a new unexpected binding mode detected by crystal structure analysis., Brenk R, Naerum L, Gradler U, Gerber HD, Garcia GA, Reuter K, Stubbs MT, Klebe G, J Med Chem. 2003 Mar 27;46(7):1133-43. PMID:12646024 Page seeded by OCA on Sat May 3 02:01:08 2008
