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Literature summary for 6.1.1.17 extracted from

  • Hu, Y.; Guerrero, E.; Keniry, M.; Manrrique, J.; Bullard, J.M.
    Identification of chemical compounds that inhibit the function of glutamyl-tRNA synthetase from Pseudomonas aeruginosa (2015), J. Biomol. Screen., 20, 1160-1170 .
    View publication on PubMedView publication on EuropePMC
Search for more literature for 6.1.1.17

Activating Compound

Activating Compound Comment Organism Structure
spermine
-
 Pseudomonas aeruginosa

Cloned(Commentary)

Cloned (Comment) Organism
gene gltX, DNA and amino acid sequence determination and analysis, sequence comparisons, recombinant enzyme expression Pseudomonas aeruginosa

Inhibitors

Inhibitors Comment Organism Structure
additional information screening of 890 synthetic compounds for inhibitory activity against enzyme GluRS, fourteen compounds with inhibitory activity are identified, overview. Minimum inhibitory concentrations (MICs) are determined for each of the compounds against a panel of pathogenic bacteria Pseudomonas aeruginosa
N'-(3-chlorophenyl)-N-(5,5-dimethyl-3-[(E)-[(2E)-3-(5-nitrofuran-2-yl)prop-2-en-1-ylidene]amino]-2-sulfanylidene-1,3-thiazolidin-4-yl)-N-hydroxyurea competitive with glutamic acid but noncompetitive with ATP Pseudomonas aeruginosa
N-(2,4-difluorophenyl)-N'-[4-[1-phenyl-3-(trifluoromethyl)-1H-pyrazol-5-yl]phenyl]urea noncompetitive with both ATP and glutamic acid Pseudomonas aeruginosa

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
additional information
-
 additional information Michaelis-Menten steady-state kinetic model Pseudomonas aeruginosa
0.00068
-
 tRNAGlu pH 7.5, 37°C Pseudomonas aeruginosa

Metals/Ions

Metals/Ions Comment Organism Structure
Mg2+ required Pseudomonas aeruginosa

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
ATP + L-glutamate + tRNAGlu Pseudomonas aeruginosa
-
 AMP + diphosphate + L-glutamyl-tRNAGlu
-
 ?
ATP + L-glutamate + tRNAGlu Pseudomonas aeruginosa ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C / PRS 101 / PAO1
-
 AMP + diphosphate + L-glutamyl-tRNAGlu
-
 ?

Organism

Organism UniProt Comment Textmining
Pseudomonas aeruginosa Q9XCL6
-
-
Pseudomonas aeruginosa ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C / PRS 101 / PAO1 Q9XCL6
-
-

Purification (Commentary)

Purification (Comment) Organism
recombinant enzyme to over 98% homogeneity Pseudomonas aeruginosa

Reaction

Reaction Comment Organism Reaction ID
ATP + L-glutamate + tRNAGlu = AMP + diphosphate + L-glutamyl-tRNAGlu a two-step reaction , in the first step, the enzyme condenses the cognate amino acid and ATP, forming an aminoacyl-adenylate intermediate with a diphosphate as the leaving group. This reaction is reversible in the absence of the tRNA. In the absence of tRNAGlu, ATP binding by GluRS is nonproductive because the alpha-phosphate of ATP and the alpha-carboxyl groups of Glu are positioned too far apart for a reaction to occur. The presence of tRNAGlu causes conformational changes surrounding the ATP binding site, allowing ATP to bind in the productive state, which moves the alpha-phosphate of the ATP closer to the alpha-carboxyl groups of Glu, allowing the reaction for the formation of the glutamyl-AMP intermediate to occur Pseudomonas aeruginosa
a

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
ATP + L-glutamate + tRNAGlu
-
 Pseudomonas aeruginosa AMP + diphosphate + L-glutamyl-tRNAGlu
-
 ?
ATP + L-glutamate + tRNAGlu
-
 Pseudomonas aeruginosa ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C / PRS 101 / PAO1 AMP + diphosphate + L-glutamyl-tRNAGlu
-
 ?
additional information Pseudomonas aeruginosa GluRS is a discriminating GluRS and requires the presence of tRNAGlu to produce a glutamyl-AMP intermediate. Development of a robust aminoacylation-based scintillation proximity assay (SPA) assay. Residue Arg147 interacts with the tRNAGlu C74 phosphate, residues Asp44 and Arg47 interact with the 2'-hydroxyl group of C75, and residues Tyr187 and Thr43 interact with the adenosine base and the 5'-hydroxyl group of A76 Pseudomonas aeruginosa ?
-
 ?
additional information Pseudomonas aeruginosa GluRS is a discriminating GluRS and requires the presence of tRNAGlu to produce a glutamyl-AMP intermediate. Development of a robust aminoacylation-based scintillation proximity assay (SPA) assay. Residue Arg147 interacts with the tRNAGlu C74 phosphate, residues Asp44 and Arg47 interact with the 2'-hydroxyl group of C75, and residues Tyr187 and Thr43 interact with the adenosine base and the 5'-hydroxyl group of A76 Pseudomonas aeruginosa ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C / PRS 101 / PAO1 ?
-
 ?

Synonyms

Synonyms Comment Organism
discriminating GluRS
-
 Pseudomonas aeruginosa
GltX
-
 Pseudomonas aeruginosa
GluRS
-
 Pseudomonas aeruginosa
Glutamyl-tRNA synthetase
-
 Pseudomonas aeruginosa

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
37
-
 assay at Pseudomonas aeruginosa

Turnover Number [1/s]

Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
0.8
-
 tRNAGlu pH 7.5, 37°C Pseudomonas aeruginosa

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
7.5
-
 assay at Pseudomonas aeruginosa

Cofactor

Cofactor Comment Organism Structure
ATP
-
 Pseudomonas aeruginosa

IC50 Value

IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
0.0219
-
 pH 7.5, 37°C Pseudomonas aeruginosa N-(2,4-difluorophenyl)-N'-[4-[1-phenyl-3-(trifluoromethyl)-1H-pyrazol-5-yl]phenyl]urea
0.0249
-
 pH 7.5, 37°C Pseudomonas aeruginosa N'-(3-chlorophenyl)-N-(5,5-dimethyl-3-[(E)-[(2E)-3-(5-nitrofuran-2-yl)prop-2-en-1-ylidene]amino]-2-sulfanylidene-1,3-thiazolidin-4-yl)-N-hydroxyurea

General Information

General Information Comment Organism
evolution the tRNA binding site is less conserved than either the Glu or the ATP binding site. Certain amino acids, including Arg147, which interacts with the tRNAGlu C74 phosphate, and Asp44 and Arg47, which interact with the 2'-hydroxyl group of C75, as well as Tyr187 and Thr43, which interact with the adenosine base and the 5'-hydroxyl group of A76, are strictly conserved Pseudomonas aeruginosa

kcat/KM [mM/s]

kcat/KM Value [1/mMs-1] kcat/KM Value Maximum [1/mMs-1] Substrate Comment Organism Structure
1176.5
-
 tRNAGlu pH 7.5, 37°C Pseudomonas aeruginosa