1N2V: Crystal Structure of TGT in complex with 2-Butyl-5,6-dihydro-1H-imidazo[4,5-d]pyridazine-4,7-dione

Citation:
Abstract
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.
PDB ID: 1N2VDownload
MMDB ID: 22661
PDB Deposition Date: 2002/10/24
Updated in MMDB: 2012/10
Experimental Method:
x-ray diffraction
Resolution: 2.1  Å
Source Organism:
Similar Structures:
Biological Unit for 1N2V: monomeric; determined by author
Molecular Components in 1N2V
Label Count Molecule
Protein (1 molecule)
1
Queuine tRNA-ribosyltransferase
Molecule annotation
Chemicals (2 molecules)
1
1
2
1
* Click molecule labels to explore molecular sequence information.

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