1P0E

CRYSTAL STRUCTURE OF ZYMOMONAS MOBILIS tRNA-GUANINE TRANSGLYCOSYLASE (TGT) COCRYSTALLISED WITH PREQ1 AT PH 5.5

Summary for 1P0E

• Entry DOI: 10.2210/pdb1p0e/pdb
• Related: 1P0B 1P0D 1PUD
• Descriptor: Queuine tRNA-ribosyltransferase, ZINC ION, 7-DEAZA-7-AMINOMETHYL-GUANINE, ... (4 entities in total)
• Functional Keywords: protein-substrate complex, transferase
• Biological source: Zymomonas mobilis
• Total number of polymer chains: 1
• Total formula weight: 43170.29

Authors

Brenk, R.,Stubbs, M.T.,Heine, A.,Reuter, K.,Klebe, G. (deposition date: 2003-04-10, release date: 2003-09-30, Last modification date: 2023-08-16)

Primary citation

Brenk, R.,Stubbs, M.T.,Heine, A.,Reuter, K.,Klebe, G.
Flexible adaptations in the structure of the tRNA-modifying enzyme tRNA-guanine transglycosylase and their implications for substrate selectivity, reaction mechanism and structure-based drug design
Chembiochem, 4:1066-1077, 2003

PubMed Abstract: The enzyme tRNA-guanine transglycosylase (TGT, EC 2.4.2.29) catalyses a base-exchange reaction that leads to anticodon modifications of certain tRNAs. The TGT enzymes of the eubacteria Zymomonas mobilis (Z. mobilis TGT) and Escherichia coli (E. coli TGT) show a different behaviour in the presence of competitive inhibitors. The active sites of both enzymes are identical apart from a single conservative amino acid exchange, namely Tyr106 of Z. mobilis TGT is replaced by a Phe in E. coli TGT. Although Tyr106 is, in contrast to Phe106, hydrogen bonded in the ligand-free structure, we can show by a mutational study of TGT(Y106F) that this is not the reason for the different responses upon competition. The TGT enzymes of various species differ in their substrate selectivity. Depending on the applied pH conditions and/or induced by ligand binding, a peptide-bond flip modulates the recognition properties of the substrate binding site, which changes between donor and acceptor functionality. Furthermore interstitial water molecules play an important role in these adaptations of the pocket. The flip of the peptide bond is further stabilised by a glutamate residue that operates as general acid/base. An active-site aspartate residue, presumed to operate as a nucleophile through covalent bonding during the base-exchange reaction, shows different conformations depending on the nature of the bound ligand. The induced-fit adaptations observed in the various TGT complex structures by multiple crystal-structure analyses are in agreement with the functional properties of the enzyme. In consequence, full understanding of this plasticity can be exploited for drug design.

PubMed: 14523925
DOI: 10.1002/cbic.200300644

Experimental method

X-RAY DIFFRACTION (2.4 Å)