4LBU

tRNA guanine transglycosylase (TGT) in complex with Furanoside-Based lin-Benzoguanine 2

4LBU の概要

• エントリーDOI: 10.2210/pdb4lbu/pdb
• 関連するPDBエントリー: 1PUD 2Z7K 3EOS 4KWO 4LEQ
• 分子名称: Queuine tRNA-ribosyltransferase, methyl 6-[6-amino-2-(methylamino)-8-oxo-7,8-dihydro-1H-imidazo[4,5-g]quinazolin-4-yl]-5,6-dideoxy-2-O-methyl-beta-D-ribo-hexofuranoside, ZINC ION, ... (6 entities in total)
• 機能のキーワード: tim barrel, glycosyltransferase, zinc-binding, transferase, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 由来する生物種: Zymomonas Mobilis subsp. mobilis
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 43851.39

構造登録者

Ehrmann, F.R.,Heine, A.,Klebe, G. (登録日: 2013-06-21, 公開日: 2014-12-24, 最終更新日: 2023-09-20)

主引用文献

Barandun, L.J.,Ehrmann, F.R.,Zimmerli, D.,Immekus, F.,Giroud, M.,Grunenfelder, C.,Schweizer, W.B.,Bernet, B.,Betz, M.,Heine, A.,Klebe, G.,Diederich, F.
Replacement of Water Molecules in a Phosphate Binding Site by Furanoside-Appended lin-Benzoguanine Ligands of tRNA-Guanine Transglycosylase (TGT).
Chemistry, 21:126-135, 2015

PubMed Abstract: The enzyme tRNA-guanine transglycosylase has been identified as a drug target for the foodborne illness shigellosis. A key challenge in structure-based design for this enzyme is the filling of the polar ribose-34 pocket. Herein, we describe a novel series of ligands consisting of furanoside-appended lin-benzoguanines. They were designed to replace a conserved water cluster and differ by the functional groups at C(2) and C(3) of the furanosyl moiety being either OH or OMe. The unfavorable desolvation of Asp102 and Asp280, which are located close to the ribose-34 pocket, had a significant impact on binding affinity. While the enzyme has tRNA as its natural substrate, X-ray co-crystal structures revealed that the furanosyl moieties of the ligands are not accommodated in the tRNA ribose-34 site, but at the location of the adjacent phosphate group. A remarkable similarity of the position of the oxygen atoms in these two structures suggests furanosides as a potential phosphate isoster.

PubMed: 25483606
DOI: 10.1002/chem.201405764

実験手法

X-RAY DIFFRACTION (1.17 Å)