A new target for shigellosis: rational design and crystallographic studies of inhibitors of tRNA-guanine transglycosylase.

摘要: Eubacterial tRNA-guanine transglycosylase (TGT) is involved in the hyper-modification of cognate tRNAs leading to exchange G34 at wobble position anticodon loop by preQ1 (2-amino-5-(aminomethyl)pyrrolo[2,3-d]pyrimidin-4(3H)-one) as part biosynthesis queuine (Q). Mutation tgt gene Shigella flexneri results a significant loss pathogenicity bacterium, revealing TGT new target for design potent drugs against Shigellosis. The X-ray structure Zymomonas mobilis complex with was used search putative inhibitors computer program LUDI. An initial screen Available Chemical Directory, database compiled from commercially available compounds, suggested several hits. Of these, 4-aminophthalhydrazide (APH) showed an inhibition constant low micromolar range. 1.95 A crystal APH Z. served starting point further modification this lead.