4LBU
tRNA guanine transglycosylase (TGT) in complex with Furanoside-Based lin-Benzoguanine 2
Summary for 4LBU
Entry DOI | 10.2210/pdb4lbu/pdb |
Related | 1PUD 2Z7K 3EOS 4KWO 4LEQ |
Descriptor | 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) |
Functional Keywords | tim barrel, glycosyltransferase, zinc-binding, transferase, transferase-transferase inhibitor complex, transferase/transferase inhibitor |
Biological source | Zymomonas Mobilis subsp. mobilis |
Total number of polymer chains | 1 |
Total formula weight | 43851.39 |
Authors | Ehrmann, F.R.,Heine, A.,Klebe, G. (deposition date: 2013-06-21, release date: 2014-12-24, Last modification date: 2023-09-20) |
Primary citation | 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 Cited by 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: 25483606DOI: 10.1002/chem.201405764 PDB entries with the same primary citation |
Experimental method | X-RAY DIFFRACTION (1.17 Å) |
Structure validation
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