Crystal structure of tRNA-guanine transglycosylase: RNA modification by base exchange

EMBO J. 1996 Jun 3;15(11):2850-7.


tRNA-guanine transglycosylases (TGT) are enzymes involved in the modification of the anticodon of tRNAs specific for Asn, Asp, His and Tyr, leading to the replacement of guanine-34 at the wobble position by the hypermodified base queuine. In prokaryotes TGT catalyzes the exchange of guanine-34 with the queuine (.)precursor 7-aminomethyl-7-deazaguanine (preQ1). The crystal structure of TGT from Zymomonas mobilis was solved by multiple isomorphous replacement and refined to a crystallographic R-factor of 19% at 1.85 angstrom resolution. The structure consists of an irregular (beta/alpha)8-barrel with a tightly attached C-terminal zinc-containing subdomain. The packing of the subdomain against the barrel is mediated by an alpha-helix, located close to the C-terminus, which displaces the eighth helix of the barrel. The structure of TGT in complex with preQ1 suggests a binding mode for tRNA where the phosphate backbone interacts with the zinc subdomain and the U33G34U35 sequence is recognized by the barrel. This model for tRNA binding is consistent with a base exchange mechanism involving a covalent tRNA-enzyme intermediate. This structure is the first example of a (beta/alpha)-barrel protein interacting specifically with a nucleic acid.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Anticodon / metabolism
  • Catalysis
  • Crystallography, X-Ray
  • Guanine / analogs & derivatives
  • Guanine / metabolism
  • Metalloproteins / ultrastructure
  • Models, Molecular
  • Molecular Sequence Data
  • Nucleic Acid Precursors / metabolism
  • Pentosyltransferases / ultrastructure*
  • Pyrimidinones / metabolism
  • Pyrroles / metabolism
  • RNA, Transfer / metabolism*
  • Recombinant Proteins
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Structure-Activity Relationship
  • Zinc / chemistry
  • Zymomonas / enzymology*


  • 7-(aminomethyl)-7-deazaguanine
  • Anticodon
  • Metalloproteins
  • Nucleic Acid Precursors
  • Pyrimidinones
  • Pyrroles
  • Recombinant Proteins
  • Guanine
  • queuine
  • RNA, Transfer
  • Pentosyltransferases
  • queuine tRNA-ribosyltransferase
  • Zinc