2HL2

Crystal structure of the editing domain of threonyl-tRNA synthetase from Pyrococcus abyssi in complex with an analog of seryladenylate

Summary for 2HL2

• Entry DOI: 10.2210/pdb2hl2/pdb
• Related: 1Y2Q 2HKZ 2HL0 2HL1
• Descriptor: Threonyl-tRNA synthetase, 5'-O-(N-(L-SERYL)-SULFAMOYL)ADENOSINE (3 entities in total)
• Functional Keywords: translation, editing, aminoacyl-trna synthetase, enzyme mechanism, enantioselectivity, ligase
• Biological source: Pyrococcus abyssi
• Cellular location: Cytoplasm: Q9UZ14
• Total number of polymer chains: 2
• Total formula weight: 33430.38

Authors

Hussain, T.,Kruparani, S.P.,Pal, B.,Sankaranarayanan, R. (deposition date: 2006-07-06, release date: 2006-08-29, Last modification date: 2023-10-25)

Primary citation

Hussain, T.,Kruparani, S.P.,Pal, B.,Dock-Bregeon, A.C.,Dwivedi, S.,Shekar, M.R.,Sureshbabu, K.,Sankaranarayanan, R.
Post-transfer editing mechanism of a D-aminoacyl-tRNA deacylase-like domain in threonyl-tRNA synthetase from archaea
Embo J., 25:4152-4162, 2006

PubMed Abstract: 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.

PubMed: 16902403
DOI: 10.1038/sj.emboj.7601278

Experimental method

X-RAY DIFFRACTION (2.6 Å)