Post-transfer editing mechanism of a D-aminoacyl-tRNA deacylase-like domain in threonyl-tRNA synthetase from archaea

EMBO J. 2006 Sep 6;25(17):4152-62. doi: 10.1038/sj.emboj.7601278. Epub 2006 Aug 10.


To ensure a high fidelity during translation, threonyl-tRNA synthetases (ThrRSs) harbor an editing domain that removes noncognate L-serine attached to tRNAThr. Most archaeal ThrRSs possess a unique editing domain structurally similar to D-aminoacyl-tRNA deacylases (DTDs) found in eubacteria and eukaryotes that specifically removes D-amino acids attached to tRNA. Here, we provide mechanistic insights into the removal of noncognate L-serine from tRNAThr by a DTD-like editing module from Pyrococcus abyssi ThrRS (Pab-NTD). High-resolution crystal structures of Pab-NTD with pre- and post-transfer substrate analogs and with L-serine show mutually nonoverlapping binding sites for the seryl moiety. Although the pre-transfer editing is excluded, the analysis reveals the importance of main chain atoms in proper positioning of the post-transfer substrate for its hydrolysis. A single residue has been shown to play a pivotal role in the inversion of enantioselectivity both in Pab-NTD and DTD. The study identifies an enantioselectivity checkpoint that filters opposite chiral molecules and thus provides a fascinating example of how nature has subtly engineered this domain for the selection of chiral molecules during translation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Archaeal Proteins / chemistry*
  • Archaeal Proteins / genetics
  • Binding Sites
  • Lysine / chemistry
  • Models, Molecular*
  • Molecular Sequence Data
  • Protein Structure, Tertiary
  • Pyrococcus abyssi / enzymology*
  • Pyrococcus abyssi / genetics
  • RNA Editing*
  • RNA, Transfer, Amino Acyl / chemistry*
  • RNA, Transfer, Amino Acyl / genetics
  • Stereoisomerism
  • Threonine-tRNA Ligase / chemistry*
  • Threonine-tRNA Ligase / genetics
  • Transfer RNA Aminoacylation


  • Archaeal Proteins
  • RNA, Transfer, Amino Acyl
  • Threonine-tRNA Ligase
  • Lysine

Associated data

  • PDB/2HKZ
  • PDB/2HL0
  • PDB/2HL1
  • PDB/2HL2