Any feedback?
Please rate this page
(literature.php)
(0/150)

BRENDA support

Literature summary for 6.1.1.3 extracted from

  • Wu, J.; Fan, Y.; Ling, J.
    Mechanism of oxidant-induced mistranslation by threonyl-tRNA synthetase (2014), Nucleic Acids Res., 42, 6523-6531 .
    View publication on PubMedView publication on EuropePMC
Search for more literature for 6.1.1.3

Protein Variants

Protein Variants Comment Organism
C182A site-directed mutagenesis, the mutation leads to loss of editing activity and to Ser misacylation to tRNAThr. C182A and C182S mutations reduce the kcat value of editing over 500fold Escherichia coli
C182S site-directed mutagenesis, the mutation leads to loss of editing activity and to Ser misacylation to tRNAThr. C182A and C182S mutations reduce the kcat value of editing over 500fold Escherichia coli
H186A site-directed mutagenesis, the mutant does not show oxidation of Cys182 by H2O2 and only partially by NaOCl Escherichia coli
H73A site-directed mutagenesis, the mutant does not show oxidation of Cys182 by H2O2 and NaOCl Escherichia coli
H77A site-directed mutagenesis, the mutant shows oxidation of Cys182 by H2O2 and NaOCl Escherichia coli

Inhibitors

Inhibitors Comment Organism Structure
H2O2 oxidation of ThrRS by H2O2 causes editing defects and Ser misincorporation at Thr codons due to oxidation of Cys182, zinc or nickel ions inhibit C182 oxidation by hydrogen peroxide. Reducing the oxidized ThrRS with DTT or sodium arsenite (NaAsO2) recovers the editing activity, cysteine residue C182 is reversibly oxidized Escherichia coli

Localization

Localization Comment Organism GeneOntology No. Textmining
cytoplasm
-
 Escherichia coli 5737
-

Metals/Ions

Metals/Ions Comment Organism Structure
Mg2+ required Escherichia coli
Ni2+ the enzyme can bind one Ni2+ per subunit, binding of nickel inhibits the oxidation of enzyme residue Cys182 by H2O2 or air Escherichia coli
Zn2+ the enzyme can bind one Zn2+ per subunit, crystal structure analysis, PDB ID 1EVK, residues C334, H385 and H511 coordinate a zinc ion, which is essential for aminoacylation. Binding of zinc inhibits the oxidation of enzyme residue Cys182 by H2O2 or air Escherichia coli

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
ATP + L-threonine + tRNAThr Escherichia coli
-
 AMP + diphosphate + L-threonyl-tRNAThr
-
 ?

Organism

Organism UniProt Comment Textmining
Escherichia coli P0A8M3 MG1655 and KY2350
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
ATP + L-threonine + tRNAThr
-
 Escherichia coli AMP + diphosphate + L-threonyl-tRNAThr
-
 ?

Subunits

Subunits Comment Organism
dimer crystal structure analysis Escherichia coli

Synonyms

Synonyms Comment Organism
Threonyl-tRNA synthetase
-
 Escherichia coli
ThrRS
-
 Escherichia coli
ThrS
-
 Escherichia coli

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
37
-
 assay at Escherichia coli

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
7.2
-
 assay at Escherichia coli

Cofactor

Cofactor Comment Organism Structure
ATP
-
 Escherichia coli

General Information

General Information Comment Organism
malfunction threonyl-tRNA synthetase (ThrRS) misactivates serine and utilizes an editing site cysteine (C182 in Escherichia coli) to hydrolyze Ser-tRNAThr. Hydrogen peroxide oxidizes C182, leading to SertRNAThr production and mistranslation of threonine codons as serine. C182 is oxidized to sulfenic acid by air, hydrogen peroxide, and hypochlorite. Air oxidation increases the Ser-tRNAThr level in the presence of elongation factor Tu. C182 forms a putative metal binding site with three conserved histidine residues (H73, H77, and H186). H73 and H186, but not H77, are critical for activating C182 for oxidation. Zinc or nickel ions inhibit C182 oxidation by hydrogen peroxide. Bacteria may use ThrRS editing to sense the oxidant levels in the environment. C182 oxidation modeling, overview. C182 is directly activated by H73 and H186 rather than by a metal ion. Chronic oxidative stress leads to ThrRS mistranslation in vivo Escherichia coli
physiological function aminoacyl-tRNA synthetases maintain the fidelity during protein synthesis by selective activation of cognate amino acids at the aminoacylation site and hydrolysis of misformed aminoacyl-tRNAs at the editing site, crystal structure PDB ID 1TJE Escherichia coli