EC Number   |
General Information |
Reference |
|---|
    6.1.1.4 | evolution |
based on sequence homology and the structures of the catalytic active sites, aaRSs are divided into two classes of 10 members each. Class I synthetases are further divided into three subclasses, a, b, and c, according to sequence homology. Leucyl-tRNA synthetase (LeuRS) belongs to class I aaRSs that include a typical Rossmann dinucleotide-binding fold active site architecture with the signature sequence modules HIGH and KMSKS. According to evolutionary models, the primitive catalytic core is extended by the insertion and/or fusion of additional domains (also called modules) in LeuRSs, most of which have inserted a large connective polypeptide 1 (CP1) domain that is responsible for amino acid editing. To ensure translation accuracy, LeuRSs have evolved a mechanism to remove aminoacyl AMP (aa-AMP, pre-transfer editing) and aa-tRNA (post-transfer editing). Sequence comparisons of the stem contact-fold domain (SC-fold) involved in editing, basic residues on helix alpha3 of the SC-fold are critical for catalytic efficiency, overview |
745321 |
| 6.1.1.4 | evolution |
based on sequence homology and the structures of the catalytic active sites, aaRSs are divided into two classes of 10 members each. Class I synthetases are further divided into three subclasses, a, b, and c, according to sequence homology. Leucyl-tRNA synthetase (LeuRS) belongs to class I aaRSs that include a typical Rossmann dinucleotide-bindingfold active site architecture with the signature sequence modules HIGH and KMSKS. According to evolutionary models, the primitive catalytic core is extended by the insertion and/or fusion of additional domains (also called modules) in LeuRSs, most of which have inserted a large connective polypeptide 1 (CP1) domain that is responsible for amino acid editing. To ensure translation accuracy, LeuRSs have evolved a mechanism to remove aminoacyl AMP (aa-AMP, pre-transfer editing) and aa-tRNA (post-transfer editing). Although post-transfer editing is carried out by the CP1 domain in most LeuRSs, this domain has been naturally deleted in LeuRS from Mycoplasma mobile (MmLeuRS). Sequence comparisons of the stem contact-fold domain (SC-fold) involved in editing, basic residues on helix alpha3 of the SC-fold are critical for catalytic efficiency, overview |
-, 745321 |
| 6.1.1.4 | evolution |
based on sequence homology and the structures of the catalytic active sites, aaRSs are divided into two classes of 10 members each. Class I synthetases are further divided into three subclasses, a, b, and c, according to sequence homology. Leucyl-tRNA synthetase (LeuRS) belongs to class I aaRSs that include a typical Rossmann dinucleotide-bindingfold active site architecture with the signature sequence modules HIGH and KMSKS. According to evolutionary models, the primitive catalytic core is extended by the insertion and/or fusion of additional domains (also called modules) in LeuRSs, most of which have inserted a large connective polypeptide 1 (CP1) domain that is responsible for amino acid editing. To ensure translation accuracy, LeuRSs have evolved a mechanism to remove aminoacyl AMP (aa-AMP, pre-transfer editing) and aa-tRNA (post-transfer editing). Sequence comparison of the EcLeuRS stem contact-fold domain (SC-fold) with editing-deficient enzymes suggests that key residues of this module have evolved an adaptive strategy to follow the editing functions of LeuRS, basic residues on helix alpha3 of the SC-fold are critical for catalytic efficiency, overview |
745321 |
| 6.1.1.4 | evolution |
based on sequence homology and the structures of the catalytic active sites, aaRSs are divided into two classes of 10 members each. Class I synthetases are further divided into three subclasses, a, b, and c, according to sequence homology. Leucyl-tRNA synthetase (LeuRS) belongs to class I aaRSs that include a typical Rossmann dinucleotide-bindingfold active site architecture with the signature sequence modules HIGH and KMSKS. According to evolutionary models, the primitive catalytic core is extended by the insertion and/or fusion of additional domains (also called modules) in LeuRSs, most of which have inserted a large connective polypeptide 1 (CP1) domain that is responsible for amino acid editing. To ensure translation accuracy, LeuRSs have evolved a mechanism to remove aminoacyl AMP (aa-AMP, pre-transfer editing) and aa-tRNA (post-transfer editing). Sequence comparisons of the stem contact-fold domain (SC-fold) involved in editing, basic residues on helix alpha3 of the SC-fold are critical for catalytic efficiency, overview |
-, 745321 |
| 6.1.1.4 | evolution |
enzyme leucyl-tRNA synthetase is part of the aminoacyl-tRNA synthetase (aaRS) family |
745503 |
| 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 |
746422 |
| 6.1.1.4 | evolution |
the family of leucyl-tRNA synthetases is divided into prokaryotic and eukaryal/archaeal groups according to the presence and position of specific insertions and extensions. e.g. the LSD1, i.e. leucine-specific domain 1, which is naturally present in eukaryal/archaeal LeuRSs, but absent from prokaryotic LeuRSs. The LSD1s from organisms of both groups are dispensable for post-transfer editing |
714086 |
| 6.1.1.4 | malfunction |
abrogation of the LeuRS specificity determinant threonine 252 does not improve the affinity of the editing site for the cognate leucine as expected, but instead substantially enhances the rate of leucyl-tRNALeu hydrolysis. Molecular dynamics simulations reveals that the wild-type enzyme, but not the T252A mutant, enforces leucine to adopt the side-chain conformation that promotes the steric exclusion of a putative catalytic water |
745556 |
| 6.1.1.4 | malfunction |
knockdown of LRS in HEK-293 cells results in impaired leucine-stimulated S6K1 phosphorylation, total amino acid stimulation of pS6K1 is also significantly reduced. Knockdown of LRS decreasesVps34 activity induced by leucine or total amino acids. Knockdown of LRS does not affect the protein levels of mTOR, raptor, Vps34, and Rag GTPases |
744654 |
| 6.1.1.4 | malfunction |
Lars knockdown does not decrease phosphorylated mTOR in differentiated myotubes, nor does it affect the hypertrophy of myotubes. Extracellular flux analysis shows that Lars knockdown does not affect the metabolism (glycolysis and mitochondrial respiration) of myotubes |
744849 |
