1F3E

A NEW TARGET FOR SHIGELLOSIS: RATIONAL DESIGN AND CRYSTALLOGRAPHIC STUDIES OF INHIBITORS OF TRNA-GUANINE TRANSGLYCOSYLASE

1F3E の概要

• エントリーDOI: 10.2210/pdb1f3e/pdb
• 関連するPDBエントリー: 1EFZ 1ENU 1PUD
• 分子名称: QUEUINE TRNA-RIBOSYLTRANSFERASE, ZINC ION, 3,5-DIAMINOPHTHALHYDRAZIDE, ... (4 entities in total)
• 機能のキーワード: trna-modifying enzyme, glycosyltransferase, transferase
• 由来する生物種: Zymomonas mobilis
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 43183.29

構造登録者

Graedler, U.,Gerber, H.-D.,Goodenough-Lashua, D.M.,Garcia, G.A.G.,Ficner, R.,Reuter, K.,Stubbs, M.T.,Klebe, G. (登録日: 2000-06-02, 公開日: 2000-06-15, 最終更新日: 2024-02-07)

主引用文献

Gradler, U.,Gerber, H.D.,Goodenough-Lashua, D.M.,Garcia, G.A.,Ficner, R.,Reuter, K.,Stubbs, M.T.,Klebe, G.
A new target for shigellosis: rational design and crystallographic studies of inhibitors of tRNA-guanine transglycosylase.
J.Mol.Biol., 306:455-467, 2001

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

PubMed: 11178905
DOI: 10.1006/jmbi.2000.4256

実験手法

X-RAY DIFFRACTION (1.85 Å)