Biology:Threonine—tRNA ligase

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threonine-tRNA ligase
EC number6.1.1.3
CAS number9023-46-5
IntEnzIntEnz view
ExPASyNiceZyme view
MetaCycmetabolic pathway
PDB structuresRCSB PDB PDBe PDBsum
Gene OntologyAmiGO / QuickGO

In enzymology, a threonine-tRNA ligase (EC is an enzyme that catalyzes the chemical reaction

ATP + L-threonine + tRNA(Thr) [math]\rightleftharpoons[/math] AMP + diphosphate + L-threonyl-tRNA(Thr)

The three substrates of this enzyme are ATP, L-threonine, and threonine-specific transfer RNA [tRNA(Thr)], whereas its three products are AMP, diphosphate, and L-threonyl-tRNA(Thr).

The systematic name of this enzyme class is L-threonine:tRNAThr ligase (AMP-forming). Other names in common use include threonyl-tRNA synthetase, threonyl-transfer ribonucleate synthetase, threonyl-transfer RNA synthetase, threonyl-transfer ribonucleic acid synthetase, threonyl ribonucleic synthetase, threonine-transfer ribonucleate synthetase, threonine translase, threonyl-tRNA synthetase, and TARS.

Threonine—tRNA ligase (TARS) belongs to the family of ligases, to be specific those forming carbon-oxygen bonds in tRNA and related compounds. More precisely, it belongs to the family of the aminoacyl-tRNA synthetases. These latter enzymes link amino acids to their cognate transfer RNAs (tRNA) in aminoacylation reactions that establish the connection between a specific amino acid and a nucleotide triplet anticodon embedded in the tRNA. During their long evolution, some of these enzymes have acquired additional functions, including roles in RNA splicing, RNA trafficking, transcriptional regulation, translational regulation, and cell signaling.

Structural studies[edit]

As of late 2007, 17 structures have been solved for this class of enzymes, with PDB accession codes 1EVK, 1EVL, 1FYF, 1KOG, 1NYQ, 1NYR, 1QF6, 1TJE, 1TKE, 1TKG, 1TKY, 1WWT, 1Y2Q, 2HKZ, 2HL0, 2HL1, and 2HL2.

Translational regulation[edit]

Threonyl-tRNA synthetase (TARS) from Escherichia coli is encoded by the thrS gene. It is a homodimeric enzyme that aminoacylates tRNA(Thr) with the amino acid threonine.[1] In addition, TARS has the ability to bind to its own messenger RNA (mRNA) immediately upstream of the AUG start codon, to inhibit its translation by competing with ribosome binding, and thus to negatively regulate the expression of its own gene. The cis-acting region responsible for the control, called operator, can be folded into four distinct domains.[2] Each of domains 2 and 4 can be folded in a stem and loop structure that mimics the anticodon arm of E. coli tRNA(Thr). Mutagenesis and biochemical experiments have shown that the two anticodon-like domains of the operator bind to the two tRNA(Thr) anticodon recognition sites (one per subunit) of the dimeric TARS in a quasi-symmetrical manner.[3][4]

The crystal structures of (i) TARS complexed with two tRNA(Thr) molecules,[5] and (ii) TARS complexed with two isolated domains 2,[6] have confirmed that TARS recognition is primarily governed by similar base-specific interactions between the anticodon loop of tRNA(Thr) and the loop of the operator domain 2. The same amino acids interact with the CGU anticodon sequence of tRNA(Thr) and the analogous residues in domain 2.


  1. Hennecke, H; Böck, A; Thomale, J; Nass, G (Sep 1977). "Threonyl-transfer ribonucleic acid synthetase from Escherichia coli: subunit structure and genetic analysis of the structural gene by means of a mutated enzyme and of a specialized transducing lambda bacteriophage". J Bacteriol 131 (3): 943–950. PMID 330505. 
  2. Brunel, C; Caillet, J; Lesage, P; Graffe, M; Dondon, J; Moine, H; Romby, P; Ehresmann, C et al. (Oct 1992). "Domains of the Escherichia coli threonyl-tRNA synthetase translational operator and their relation to threonine tRNA isoacceptors". J Mol Biol 227 (3): 621–634. doi:10.1016/0022-2836(92)90212-3. PMID 1383551. 
  3. Bedouelle, Hugues (Apr 1993). "Symmetrical interactions between the translational operator of the thrS gene and dimeric threonyl transfer RNA synthetase". J Mol Biol 230 (3): 704–708. doi:10.1006/jmbi.1993.1190. PMID 7683056. 
  4. Romby, P; Caillet, J; Ebel, C; Sacerdot, C; Graffe, M; Eyermann, F; Brunel, C; Moine, H et al. (Nov 1996). "The expression of E.coli threonyl-tRNA synthetase is regulated at the translational level by symmetrical operator-repressor interactions". EMBO J 15 (21): 5976–5987. PMID 8918475. 
  5. Sankaranarayanan, R; Dock-Bregeon, AC; Romby, P; Caillet, J; Springer, M; Rees, B; Ehresmann, C; Ehresmann, B et al. (Apr 1999). "The structure of threonyl-tRNA synthetase-tRNA(Thr) complex enlightens its repressor activity and reveals an essential zinc ion in the active site". Cell 97 (3): 371–381. doi:10.1016/s0092-8674(00)80746-1. PMID 10319817. 
  6. Torres-Larios, A; Dock-Bregeon, AC; Romby, P; Rees, B; Sankaranarayanan, R; Caillet, J; Springer, M; Ehresmann, C et al. (May 2002). "Structural basis of translational control by Escherichia coli threonyl tRNA synthetase". Nat Struct Biol 9 (5): 343–347. doi:10.1038/nsb789. PMID 11953757. 

Further reading[edit]

  • "Incorporation of amino acids into ribonucleic acid. I. The role of activating enzymes". J. Biol. Chem. 235: 1061–7. 1960. PMID 13792726. 
  • "Partial purification of the threonine- and tyrosine-activating enzymes from rat liver, and the effect of patassium ions on the activity of the tyrosine enzyme". J. Biol. Chem. 236: 197–9. 1961. PMID 13715350.—tRNA ligase was the original source. Read more.