Structural basis of the initial binding of tRNA(Ile) lysidine synthetase TilS with ATP and L-lysine

Structure. 2007 Dec;15(12):1642-53. doi: 10.1016/j.str.2007.09.020.

Abstract

In the bacterial genetic-code system, the codon AUA is decoded as isoleucine by tRNA(Ile)(2) with the lysidine residue at the wobble position. Lysidine is derived from cytidine, with ATP and L-lysine, by tRNA(Ile) lysidine synthetase (TilS), which is an N-type ATP pyrophosphatase. In this study, we determined the crystal structure of Aquifex aeolicus TilS, complexed with ATP, Mg2+, and L-lysine, at 2.5 A resolution. The presence of the TilS-specific subdomain causes the active site to have two separate gateways, a large hole and a narrow tunnel on the opposite side. ATP is bound inside the hole, and L-lysine is bound at the entrance of the tunnel. The conserved Asp36 in the PP-motif coordinates Mg2+. In these initial binding modes, the ATP, Mg2+, and L-lysine are held far apart from each other, but they seem to be brought together for the reaction upon cytidine binding, with putative structural changes of the complex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / chemistry
  • Adenosine Triphosphate / metabolism*
  • Amino Acid Sequence
  • Amino Acyl-tRNA Synthetases / chemistry
  • Amino Acyl-tRNA Synthetases / metabolism*
  • Lysine / chemistry
  • Lysine / metabolism*
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Binding
  • Protein Conformation
  • Sequence Homology, Amino Acid

Substances

  • Adenosine Triphosphate
  • Amino Acyl-tRNA Synthetases
  • Lysine

Associated data

  • PDB/2E21
  • PDB/2E89