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

BRENDA support

Literature summary extracted from

  • Huang, Q.; Zhou, X.L.; Hu, Q.H.; Lei, H.Y.; Fang, Z.P.; Yao, P.; Wang, E.D.
    A bridge between the aminoacylation and editing domains of leucyl-tRNA synthetase is crucial for its synthetic activity (2014), RNA, 20, 1440-1450 .
    View publication on PubMedView publication on EuropePMC

Protein Variants

EC Number Protein Variants Comment Organism
6.1.1.4 A525S site-directed mutagenesis, the mutant shows altered kinetics and reduced catalytic efficiency in the aminoacylation reaction compared to the wild-type enzyme Homo sapiens
6.1.1.4 C527E site-directed mutagenesis, the mutant shows altered kinetics and reduced catalytic efficiency in the aminoacylation reaction compared to the wild-type enzyme Homo sapiens
6.1.1.4 D250A site-directed mutagenesis, the mutant shows altered kinetics and reduced catalytic efficiency in the aminoacylation reaction compared to the wild-type enzyme Homo sapiens
6.1.1.4 D250E site-directed mutagenesis, the mutant shows slightly altered kinetics and slightly reduced catalytic efficiency in the aminoacylation reaction compared to the wild-type enzyme Homo sapiens
6.1.1.4 D250N site-directed mutagenesis, the mutant shows altered kinetics and reduced catalytic efficiency in the aminoacylation reaction compared to the wild-type enzyme Homo sapiens
6.1.1.4 D250R site-directed mutagenesis, inactive mutant Homo sapiens
6.1.1.4 D252R site-directed mutagenesis, inactive mutant Homo sapiens
6.1.1.4 D528R site-directed mutagenesis, the mutant shows altered kinetics, reduced catalytic efficiency in the aminoacylation reaction, and 85% reduced amino acid activation activity compared to the wild-type enzyme Homo sapiens
6.1.1.4 G245A site-directed mutagenesis, the mutant shows altered kinetics and reduced catalytic efficiency in the aminoacylation reaction compared to the wild-type enzyme Homo sapiens
6.1.1.4 G245D site-directed mutagenesis, the mutant shows altered kinetics and 50% reduced catalytic efficiency in the aminoacylation reaction compared to the wild-type enzyme Homo sapiens
6.1.1.4 G245P site-directed mutagenesis, inactive mutant Homo sapiens
6.1.1.4 G245R site-directed mutagenesis, the mutant shows altered kinetics and 50% reduced catalytic efficiency in the aminoacylation reaction compared to the wild-type enzyme Homo sapiens
6.1.1.4 H251D site-directed mutagenesis, inactive mutant Homo sapiens
6.1.1.4 additional information the CP1 hairpin of Homo sapiens cytoplasmic LeuRS (hcLeuRS) is deleted or substituted by those from other representative species. Lack of a CP1 hairpin leads to complete loss of aminoacylation, amino acid activation, and tRNA binding, butthe mutants retain post-transfer editing activity. Only the CP1 hairpin from Saccharomyces cerevisiae LeuRS (ScLeuRS) can partly rescue the hcLeuRS functions. Construction of chimeric mutants with the CP1 hairpin of hcLeuRS substituted for that of hcIleRS or hcValRS. The deacylating activity toward mischarged tRNALeu of hcLeuRS-ScCH1 and -ScCH2 decreases by 15% compared to that of hcLeuRS, kinetics comparisons, overview. Further site-directed mutagenesis indicates that the flexibility of small residues and the charge of polar residues in the CP1 hairpin are crucial for the function of LeuRS Homo sapiens
6.1.1.4 P242E site-directed mutagenesis, the mutant shows altered kinetics and reduced catalytic efficiency in the aminoacylation reaction compared to the wild-type enzyme Homo sapiens
6.1.1.4 P247A site-directed mutagenesis, the mutant shows altered kinetics and reduced catalytic efficiency in the aminoacylation reaction compared to the wild-type enzyme Homo sapiens
6.1.1.4 Q529A site-directed mutagenesis, the mutant shows altered kinetics, reduced catalytic efficiency in the aminoacylation reaction, and 70% reduced amino acid activation activity compared to the wild-type enzyme Homo sapiens
6.1.1.4 R236D site-directed mutagenesis, the mutant shows altered kinetics, reduced catalytic efficiency in the aminoacylation reaction, and 30% reduced amino acid activation activity compared to the wild-type enzyme Homo sapiens
6.1.1.4 R517D site-directed mutagenesis, the mutant shows altered kinetics, reduced catalytic efficiency in the aminoacylation reaction, and 90% reduced amino acid activation activity compared to the wild-type enzyme Homo sapiens
6.1.1.4 S519G site-directed mutagenesis, the mutant shows altered kinetics and reduced catalytic efficiency in the aminoacylation reaction compared to the wild-type enzyme Homo sapiens
6.1.1.4 V523I site-directed mutagenesis, the mutant shows altered kinetics and reduced catalytic efficiency in the aminoacylation reaction compared to the wild-type enzyme Homo sapiens
6.1.1.4 W530A site-directed mutagenesis, the mutant shows altered kinetics, reduced catalytic efficiency in the aminoacylation reaction, and 50% reduced amino acid activation activity compared to the wild-type enzyme Homo sapiens
6.1.1.4 Y240A site-directed mutagenesis, the mutant shows altered kinetics, reduced catalytic efficiency in the aminoacylation reaction, and 50% reduced amino acid activation activity compared to the wild-type enzyme Homo sapiens
6.1.1.4 Y531A site-directed mutagenesis, the mutant shows altered kinetics, reduced catalytic efficiency in the aminoacylation reaction, and 50% reduced amino acid activation activity compared to the wild-type enzyme Homo sapiens
6.1.1.4 Y534A site-directed mutagenesis, the mutant shows altered kinetics, reduced catalytic efficiency in the aminoacylation reaction, and 60% reduced amino acid activation activity compared to the wild-type enzyme Homo sapiens

KM Value [mM]

EC Number KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
6.1.1.4 additional information
-
 additional information kinetics of aminoacylation reaction of recombinant wild-type and mutant enzymes, and apparent kinetic parameters for hydrolytic editing of mischarged Met-tRNALeu, overview Homo sapiens

Localization

EC Number Localization Comment Organism GeneOntology No. Textmining
6.1.1.4 cytoplasm
-
 Homo sapiens 5737
-

Metals/Ions

EC Number Metals/Ions Comment Organism Structure
6.1.1.4 Mg2+ required Homo sapiens

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
6.1.1.4 ATP + L-leucine + tRNALeu Homo sapiens
-
 AMP + diphosphate + L-leucyl-tRNALeu
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
6.1.1.4 Homo sapiens Q9P2J5
-
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
6.1.1.4 ATP + L-leucine + tRNALeu
-
 Homo sapiens AMP + diphosphate + L-leucyl-tRNALeu
-
 ?

Subunits

EC Number Subunits Comment Organism
6.1.1.4 More enzyme LeuRS contains a catalysis domain (aminoacylation) and a CP1 domain (editing). CP1, residue R236 to G256, is inserted 35 A away from the aminoacylation domain. Aminoacylation and editing require CP1 to swing to the coordinated conformation. The neck between the CP1 domain and the aminoacylation domain is defined as the CP1 hairpin. The location of the CP1 hairpin suggests a crucial role in the CP1 swing and domain-domain interaction. Besides the conservative Rossmann fold, almost all LeuRSs contain a large insertion domain called connective peptide 1 (CP1) within the sequence of the catalytic core. CP1 folds independently in the tertiary structure and is defined as a classic editing domain, in which the aminoacyl bond of mischarged aatRNA is hydrolyzed (post-transfer editing) to ensure the fidelity of the catalytic process. Primary sequence and tertiary structure of the CP1 hairpin of LeuRS, and structure-function relationship, overview Homo sapiens

Synonyms

EC Number Synonyms Comment Organism
6.1.1.4 cytoplasmic LeuRS
-
 Homo sapiens
6.1.1.4 HcleuRS
-
 Homo sapiens
6.1.1.4 LARS
-
 Homo sapiens
6.1.1.4 Leucyl-tRNA synthetase
-
 Homo sapiens
6.1.1.4 LeuRS
-
 Homo sapiens

Cofactor

EC Number Cofactor Comment Organism Structure
6.1.1.4 ATP
-
 Homo sapiens

General Information

EC Number General Information Comment Organism
6.1.1.4 evolution leucyl-tRNA synthetase (LeuRS) belongs to class Ia aminoacyl-tRNA synthetases (AaRSs). Based on their similar structures, LeuRS, IleRS, and ValRS are collectively known as LIVRS, all of which contain a representative catalytic core consisting of a Rossmann fold. Besides the conservative Rossmann fold, almost all LeuRSs contain a large insertion domain called connective peptide 1 (CP1) within the sequence of the catalytic core. CP1 folds independently in the tertiary structure and is defined as a classic editing domain, in which the aminoacyl bond of mischarged aatRNA is hydrolyzed (post-transfer editing) to ensure the fidelity of the catalytic process Homo sapiens
6.1.1.4 additional information the CP1 hairpin editing structure, residue R236 to G256, and the flexibility of small residues and the charge of polar residues in the CP1 hairpin are crucial for the function of LeuRS. The CP1 hairpin domain is crucial for activities of leucine, leucylation of tRNALeu, and tRNA binding of hcLeuRS Homo sapiens
6.1.1.4 physiological function leucyl-tRNA synthetases (LeuRSs) catalyze the linkage of leucine with tRNALeu Homo sapiens