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ATP + L-isoleucine + tRNALeu
AMP + diphosphate + L-isoleucyl-tRNALeu
-
-
-
?
ATP + L-leucine + tRNACAGLeu
AMP + diphosphate + L-leucyl-tRNACAGLeu
human cytoplasmic tRNACAGLeu (hctRNACAG)
-
-
?
ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
L-isoleucyl-tRNALeu + H2O
t-RNALeu + L-isoleucine
-
editing activity
-
?
ATP + L-isoleucine + tRNALeu
AMP + diphosphate + L-isoleucyl-tRNALeu
ATP + L-leucine + tRNAIle
AMP + diphosphate + L-leucyl-tRNALeu
-
-
-
?
ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
ATP + L-leucine + tRNALeu(UUR)
AMP + diphosphate + L-leucyl-tRNALeu(UUR)
-
leucyl-tRNA synthetase contacts tRNALeu(UUR) in the amino acid acid acceptor stem, the anticodon stem, and the D-loop
-
-
?
ATP + L-leucine + tRNALeuCUN
AMP + diphosphate + L-leucyl-tRNALeuCUN
-
-
-
-
?
ATP + L-leucine + tRNALeuUUR
AMP + diphosphate + L-leucyl-tRNALeuUUR
-
-
-
-
?
additional information
?
-
ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
-
-
?
ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
-
-
-
?
ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
-
-
?
ATP + L-isoleucine + tRNALeu
AMP + diphosphate + L-isoleucyl-tRNALeu
-
-
-
-
?
ATP + L-isoleucine + tRNALeu
AMP + diphosphate + L-isoleucyl-tRNALeu
-
the ratio of turnover number to KM-value for L-leucine is 3000fold higher than the ratio observed for L-isoleucine
-
-
?
ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
-
-
?
ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
-
-
-
?
ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
-
?
ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
tRNALeu substrate from Escherichia coli, 2-step reaction, the first step is reversible, while the second step is not
-
?
ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
human cytosolic leucyl-tRNA synthetase is one component of a macromolecular aminoacyl-tRNA synthetase complex. The C-terminal peptide of hcLeuRS is critical for the interaction with hcArgRS and the interaction in the multi-tRNA synthetase complex
-
-
?
ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
human mitochondrial LeuRS achieves high aminoacylation fidelity without a functional editing active site, representing a rare example of a class I aminoacyl-tRNA synthetase that does not proofread its products, K600 strongly impacts aminoacylation in two ways: it affects both amino acid discrimination and tRNA binding, overview
-
-
?
additional information
?
-
-
activity with mitochondrial tRNA mutants associated with some human mitochondrion-related neuromuscular disorders
-
?
additional information
?
-
enzyme also performs the ATP-diphosphate exchange reaction
-
?
additional information
?
-
-
enzyme also performs the ATP-diphosphate exchange reaction
-
?
additional information
?
-
-
LeuRS misactivates several non-cognate amino acids, e.g. Ile and Met as well as the non-standard amino acids norvaline and alpha-amino butyrate. It uses mainly pre-transfer editing to edit alpha-amino butyrate and a tRNA-dependent mechanism to edit norvaline, although both amino acids can be charged to tRNALeu, overview. Separation of the norvaline-editing pathways
-
-
?
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5-(5-chloro-2-hydroxy-phenylamino)-2H-[1,2,4]triazin-3-one
binding mode, overview
5-(5-chloro-2-hydroxy-phenylamino)-6-methyl-2H-[1,2,4]triazin-3-one
binding mode, overview
6,8-dibenzyl-2-(4-methylphenyl)-4,7-dioxo-N-(prop-2-en-1-yl)hexahydro-2H-pyrazino[2,1-c][1,2,4]triazine-1(6H)-carboxamide
-
8-benzyl-6-[(4-chlorophenyl)methyl]-2-(4-methylphenyl)-4,7-dioxo-N-(prop-2-en-1-yl)hexahydro-2H-pyrazino[2,1-c][1,2,4]triazine-1(6H)-carboxamide
-
8-benzyl-N-([1,1'-biphenyl]-2-yl)-2-methyl-4,7-dioxo-6-(propan-2-yl)hexahydro-2H-pyrazino[2,1-c][1,2,4]triazine-1(6H)-carboxamide
-
N,8-dibenzyl-6-[(4-hydroxyphenyl)methyl]-2-methyl-4,7-dioxohexahydro-2H-pyrazino[2,1-c][1,2,4]triazine-1(6H)-carboxamide
-
N-(4-fluorophenyl)-8-[(furan-2-yl)methyl]-2-methyl-4,7-dioxo-6-[3-[N'-(2,2,4,6,7-pentamethyl-2,3-dihydro-1-benzofuran-5-yl)carbamimidamido]propyl]hexahydro-2H-pyrazino[2,1-c][1,2,4]triazine-1(6H)-carboxamide
-
N-benzyl-8-butyl-2-(4-methylphenyl)-4,7-dioxo-6-(propan-2-yl)hexahydro-2H-pyrazino[2,1-c][1,2,4]triazine-1(6H)-carboxamide
-
N-benzyl-8-butyl-6-[(4-chlorophenyl)methyl]-2-(4-methylphenyl)-4,7-dioxohexahydro-2H-pyrazino[2,1-c][1,2,4]triazine-1(6H)-carboxamide
-
N-benzyl-8-[(furan-2-yl)methyl]-2-(4-methylphenyl)-4,7-dioxo-6-(propan-2-yl)hexahydro-2H-pyrazino[2,1-c][1,2,4]triazine-1(6H)-carboxamide
-
5-fluoro-2,1-benzoxaborol-1(3H)-ol
-
AN-2690, antibiotic which specifically targets the editing active site of LeuRS
BC-LI-0186
-
the interaction between RagD and LRS is disrupted by compound BC-LI-0186 inhibitong the translocation of the enzyme to the lysosome
additional information
derivatives of 5-phenylamino-2H-[1,2,4]triazin-3-one as leucyl-tRNA synthetase (LeuRS) inhibitors, docking study, overview. The inhibitory activity of some compounds against pathogenic LeuRS is 10fold higher compared to the human enzyme. Hydrogen bond-foming amino acids in active site of LeuRS are Phe97, Tyr99, Glu103, His109, Tyr113, Asp137, Ser631, Gly678, Glu680, His681, Gln714, Ile717, Lys759, and Ile760
-
additional information
-
derivatives of 5-phenylamino-2H-[1,2,4]triazin-3-one as leucyl-tRNA synthetase (LeuRS) inhibitors, docking study, overview. The inhibitory activity of some compounds against pathogenic LeuRS is 10fold higher compared to the human enzyme. Hydrogen bond-foming amino acids in active site of LeuRS are Phe97, Tyr99, Glu103, His109, Tyr113, Asp137, Ser631, Gly678, Glu680, His681, Gln714, Ile717, Lys759, and Ile760
-
additional information
design and synthesis of tetra-substituted hexahydro-4H-pyrazino[2,1-c][1,2,4]triazine-4,7(6H)-diones as beta-turn mimetics via tandem N-acyliminium cyclization using a parallel synthetic strategy involving both solid and solution-phase reactions. Construction of a 162-member library of tetra-substituted pyrazinotriazinediones with an average purity of 90% using a solid-phase parallel synthesis platform, and screening for the LRS-RagD interaction inhibition by the compounds, overview
-
additional information
inhibition by high levels of mono- and divalent cations
-
additional information
-
inhibition by high levels of mono- and divalent cations
-
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Acidosis, Lactic
Correction for Li and Guan, "Human Mitochondrial Leucyl-tRNA Synthetase Corrects Mitochondrial Dysfunctions Due to the tRNA(Leu(UUR)) A3243G Mutation, Associated with Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-Like Symptoms and Diabetes".
Acidosis, Lactic
Human mitochondrial leucyl-tRNA synthetase corrects mitochondrial dysfunctions due to the tRNALeu(UUR) A3243G mutation, associated with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like symptoms and diabetes.
Acidosis, Lactic
LARS2 Variants Associated with Hydrops, Lactic Acidosis, Sideroblastic Anemia, and Multisystem Failure.
Acidosis, Lactic
The expanding LARS2 phenotypic spectrum: HLASA, Perrault syndrome with leukodystrophy, and mitochondrial myopathy.
Anemia
Severe course with lethal hepatocellular injury and skeletal muscular dysgenesis in a neonate with infantile liver failure syndrome type 1 caused by novel LARS1 mutations.
Anemia, Sideroblastic
LARS2 Variants Associated with Hydrops, Lactic Acidosis, Sideroblastic Anemia, and Multisystem Failure.
Anemia, Sideroblastic
The expanding LARS2 phenotypic spectrum: HLASA, Perrault syndrome with leukodystrophy, and mitochondrial myopathy.
Carcinogenesis
Implication of leucyl-tRNA synthetase 1 (LARS1) over-expression in growth and migration of lung cancer cells detected by siRNA targeted knock-down analysis.
Carcinogenesis
Inactivation of LARS2, located at the commonly deleted region 3p21.3, by both epigenetic and genetic mechanisms in nasopharyngeal carcinoma.
Carcinoma, Non-Small-Cell Lung
Therapeutic effects of the novel Leucyl-tRNA synthetase inhibitor BC-LI-0186 in non-small cell lung cancer.
CHARGE Syndrome
Laser-capture micro dissection combined with next-generation sequencing analysis of cell type-specific deafness gene expression in the mouse cochlea.
Coma
Prognostic value of time-related Glasgow Coma Scale components in severe traumatic brain injury: a prospective evaluation with respect to 1-year survival and functional outcome.
Confusion
Homosexuality in ancient and modern Korea.
COVID-19
Instagram as a virtual art display for medical students.
Deafness
Biallelic variants in LARS2 and KARS cause deafness and (ovario)leukodystrophy.
Deafness
Characterization of a knock-in mouse model of the homozygous p.V37I variant in Gjb2.
Deafness
The expanding LARS2 phenotypic spectrum: HLASA, Perrault syndrome with leukodystrophy, and mitochondrial myopathy.
Diabetes Mellitus, Type 2
Evidence that the mitochondrial leucyl tRNA synthetase (LARS2) gene represents a novel type 2 diabetes susceptibility gene.
Diabetes Mellitus, Type 2
Genetic association analysis of LARS2 with type 2 diabetes.
Fetal Growth Retardation
Severe course with lethal hepatocellular injury and skeletal muscular dysgenesis in a neonate with infantile liver failure syndrome type 1 caused by novel LARS1 mutations.
Gram-Negative Bacterial Infections
An assessment of the genetic toxicology of novel boron-containing therapeutic agents.
Hearing Loss
LARS2 Variants Associated with Hydrops, Lactic Acidosis, Sideroblastic Anemia, and Multisystem Failure.
Hearing Loss
Laser-capture micro dissection combined with next-generation sequencing analysis of cell type-specific deafness gene expression in the mouse cochlea.
Hearing Loss
Mutations in LARS2, Encoding Mitochondrial Leucyl-tRNA Synthetase, Lead to Premature Ovarian Failure and Hearing Loss in Perrault Syndrome.
Hearing Loss
Novel Mutations in CLPP, LARS2, CDH23, and COL4A5 Identified in Familial Cases of Prelingual Hearing Loss.
Hearing Loss
The expanding LARS2 phenotypic spectrum: HLASA, Perrault syndrome with leukodystrophy, and mitochondrial myopathy.
Hearing Loss, Sensorineural
Marfanoid habitus is a nonspecific feature of Perrault syndrome.
Hypertension
Prevalence and perinatal outcomes of non-communicable diseases in pregnancy in a regional hospital in Haiti: A prospective cohort study.
Infections
Bacterial resistance to leucyl-tRNA synthetase inhibitor GSK2251052 develops during treatment of complicated urinary tract infections.
Infections
Directive clinique no 409 : Tests diagnostiques ftaux intra-utérins en cas d'infection virale chronique maternelle.
Infections
Discovery of a potent benzoxaborole-based anti-pneumococcal agent targeting leucyl-tRNA synthetase.
Infections
Recent development of leucyl-tRNA synthetase inhibitors as antimicrobial agents.
Kallmann Syndrome
Laser-capture micro dissection combined with next-generation sequencing analysis of cell type-specific deafness gene expression in the mouse cochlea.
leucine-trna ligase deficiency
Leucyl-tRNA synthetase deficiency systemically induces excessive autophagy in zebrafish.
Liver Failure
Deep phenotyping of MARS1 (interstitial lung and liver disease) and LARS1 (infantile liver failure syndrome 1) recessive multisystemic disease using Human Phenotype Ontology annotation: Overlap and differences. Case report and review of literature.
Liver Failure
Genotypic diversity and phenotypic spectrum of infantile liver failure syndrome type 1 due to variants in LARS1.
Liver Failure
Infantile Liver Failure Syndrome 1 associated with a novel variant of the LARS1 gene: Clinical, genetic, and functional characterization.
Liver Failure
Severe course with lethal hepatocellular injury and skeletal muscular dysgenesis in a neonate with infantile liver failure syndrome type 1 caused by novel LARS1 mutations.
Liver Failure
[Clinical feature and molecular diagnostic analysis of the first non-caucasian child with infantile liver failure syndrome type 1].
Liver Failure, Acute
Severe course with lethal hepatocellular injury and skeletal muscular dysgenesis in a neonate with infantile liver failure syndrome type 1 caused by novel LARS1 mutations.
Lung Diseases
A Leucyl-tRNA Synthetase Inhibitor with Broad-Spectrum Anti-Mycobacterial Activity.
Lung Neoplasms
Implication of leucyl-tRNA synthetase 1 (LARS1) over-expression in growth and migration of lung cancer cells detected by siRNA targeted knock-down analysis.
Lung Neoplasms
Therapeutic effects of the novel Leucyl-tRNA synthetase inhibitor BC-LI-0186 in non-small cell lung cancer.
Malaria
Recent development of leucyl-tRNA synthetase inhibitors as antimicrobial agents.
Mandibulofacial Dysostosis
Laser-capture micro dissection combined with next-generation sequencing analysis of cell type-specific deafness gene expression in the mouse cochlea.
MELAS Syndrome
Correction of the consequences of mitochondrial 3243A>G mutation in the MT-TL1 gene causing the MELAS syndrome by tRNA import into mitochondria.
MELAS Syndrome
Exploring the Ability of LARS2 Carboxy-Terminal Domain in Rescuing the MELAS Phenotype.
Migraine Disorders
Samuel Auguste Tissot (1728-1797). His research on migraine.
Mitochondrial Diseases
Biallelic variants in LARS2 and KARS cause deafness and (ovario)leukodystrophy.
Mitochondrial Encephalomyopathies
Correction for Li and Guan, "Human Mitochondrial Leucyl-tRNA Synthetase Corrects Mitochondrial Dysfunctions Due to the tRNA(Leu(UUR)) A3243G Mutation, Associated with Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-Like Symptoms and Diabetes".
Mitochondrial Encephalomyopathies
Human mitochondrial leucyl-tRNA synthetase corrects mitochondrial dysfunctions due to the tRNALeu(UUR) A3243G mutation, associated with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like symptoms and diabetes.
Mitochondrial Myopathies
The expanding LARS2 phenotypic spectrum: HLASA, Perrault syndrome with leukodystrophy, and mitochondrial myopathy.
Muscular Diseases
The expanding LARS2 phenotypic spectrum: HLASA, Perrault syndrome with leukodystrophy, and mitochondrial myopathy.
Mycoses
Recent development of leucyl-tRNA synthetase inhibitors as antimicrobial agents.
Nasopharyngeal Carcinoma
Inactivation of LARS2, located at the commonly deleted region 3p21.3, by both epigenetic and genetic mechanisms in nasopharyngeal carcinoma.
Nasopharyngitis
Inactivation of LARS2, located at the commonly deleted region 3p21.3, by both epigenetic and genetic mechanisms in nasopharyngeal carcinoma.
Neoplasms
An In Vivo Gain-of-Function Screen Identifies the Williams-Beuren Syndrome Gene GTF2IRD1 as a Mammary Tumor Promoter.
Neoplasms
Avoir sa santé en main : le sentiment d'habilitation tel que perçu par les jeunes adultes souffrant d'un cancer avancé.
Neoplasms
Concept d'adaptation chez les conjoints de femmes iraniennes atteintes du cancer du sein: étude qualitative basée sur une approche phénoménologique.
Neoplasms
Connaissances, attitudes et croyances concernant le dépistage du cancer du col utérin dans le District d'Ajumako-Enyan-Essiam au Ghana.
Neoplasms
Degrés de collaboration perçus entre les patients atteints de cancer et leurs prestataires de soins pendant la radiothérapie.
Neoplasms
Élaboration d'un énoncé de position national sur la navigation des patients atteints de cancer au Canada.
Neoplasms
Implication of leucyl-tRNA synthetase 1 (LARS1) over-expression in growth and migration of lung cancer cells detected by siRNA targeted knock-down analysis.
Neoplasms
Leucyl-tRNA synthetase 1 is required for proliferation of TSC-null cells.
Neoplasms
Optimiser les soins des adultes âgés atteints de cancer et l'accompagnement de leurs proches: énoncé de position et contribution des infirmières canadiennes en oncologie.
Neoplasms
Plant tumour biocontrol agent employs a tRNA-dependent mechanism to inhibit leucyl-tRNA synthetase.
Neoplasms
Retour au travail de patients atteints de cancer.
Nephritis, Hereditary
Laser-capture micro dissection combined with next-generation sequencing analysis of cell type-specific deafness gene expression in the mouse cochlea.
Neurologic Manifestations
Biallelic mutations in LARS2 can cause Perrault syndrome type 2 with neurologic symptoms.
Onychomycosis
An antifungal agent inhibits an aminoacyl-tRNA synthetase by trapping tRNA in the editing site.
Pediatric Obesity
Prendre le virage des partenariats.
Primary Ovarian Insufficiency
Biallelic variants in LARS2 and KARS cause deafness and (ovario)leukodystrophy.
Primary Ovarian Insufficiency
LARS2 Variants Associated with Hydrops, Lactic Acidosis, Sideroblastic Anemia, and Multisystem Failure.
Primary Ovarian Insufficiency
Marfanoid habitus is a nonspecific feature of Perrault syndrome.
Primary Ovarian Insufficiency
Mutations in LARS2, Encoding Mitochondrial Leucyl-tRNA Synthetase, Lead to Premature Ovarian Failure and Hearing Loss in Perrault Syndrome.
Primary Ovarian Insufficiency
The expanding LARS2 phenotypic spectrum: HLASA, Perrault syndrome with leukodystrophy, and mitochondrial myopathy.
Squamous Cell Carcinoma of Head and Neck
Promoter methylation of cyclin A1 is associated with human papillomavirus 16 induced head and neck squamous cell carcinoma independently of p53 mutation.
Starvation
Glucose Starvation Blocks Translation at Multiple Levels.
Starvation
Glucose-dependent control of leucine metabolism by leucyl-tRNA synthetase 1.
Starvation
In vivo regulatory responses of four Escherichia coli operons which encode leucyl-tRNAs.
Starvation
Membrane association of leucyl-tRNA synthetase during leucine starvation in Escherichia coli.
Starvation
Mitochondrial leucine tRNA level and PTCD1 are regulated in response to leucine starvation.
Starvation
Regulation of the nuclear genes encoding the cytoplasmic and mitochondrial leucyl-tRNA synthetases of Neurospora crassa.
Starvation
Yeast proteinase yscB inactivates the leucyl tRNA synthetase in extracts of Saccharomyces cerevisiae.
Stroke
A video-game group intervention: Experiences and perceptions of adults with chronic stroke and their therapists: Intervention de groupe à l'aide de jeux vidéo : Expériences et perceptions d'adultes en phase chronique d'un accident vasculaire cérébral et de leurs ergothérapeutes.
Tuberculosis
A Leucyl-tRNA Synthetase Inhibitor with Broad-Spectrum Anti-Mycobacterial Activity.
Tuberculosis
A prokaryote and human tRNA synthetase provide an essential RNA splicing function in yeast mitochondria.
Tuberculosis
Crucial role of the C-terminal domain of Mycobacterium tuberculosis leucyl-tRNA synthetase in aminoacylation and editing.
Tuberculosis
Discovery of a Potent and Specific M. tuberculosis Leucyl-tRNA Synthetase Inhibitor: (S)-3-(Aminomethyl)-4-chloro-7-(2-hydroxyethoxy)benzo[c][1,2]oxaborol-1(3H)-ol (GSK656).
Tuberculosis
Discovery of novel antituberculosis agents among 3-phenyl-5-(1-phenyl-1H-[1,2,3]triazol-4-yl)-[1,2,4]oxadiazole derivatives targeting aminoacyl-tRNA synthetases.
Tuberculosis
Discovery of novel oral protein synthesis inhibitors of Mycobacterium tuberculosis that target leucyl-tRNA synthetase.
Tuberculosis
Discovery of potent anti-tuberculosis agents targeting leucyl-tRNA synthetase.
Tuberculosis
Dual-target inhibitors of mycobacterial aminoacyl-tRNA synthetases among N-benzylidene-N'-thiazol-2-yl-hydrazines.
Tuberculosis
Dual-targeted hit identification using pharmacophore screening.
Tuberculosis
First-Time-in-Human Study and Prediction of Early Bactericidal Activity for GSK3036656, a Potent Leucyl-tRNA Synthetase Inhibitor for Tuberculosis Treatment.
Tuberculosis
Identification of Mycobacterium tuberculosis leucyl-tRNA synthetase (LeuRS) inhibitors among the derivatives of 5-phenylamino-2H-[1,2,4]triazin-3-one.
Tuberculosis
In Vitro Susceptibility Testing of GSK656 against Mycobacterium Species.
Urinary Tract Infections
Bacterial resistance to leucyl-tRNA synthetase inhibitor GSK2251052 develops during treatment of complicated urinary tract infections.
Usher Syndromes
Laser-capture micro dissection combined with next-generation sequencing analysis of cell type-specific deafness gene expression in the mouse cochlea.
Waardenburg Syndrome
Laser-capture micro dissection combined with next-generation sequencing analysis of cell type-specific deafness gene expression in the mouse cochlea.
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0.00074 - 0.0017
tRNACAGLeu
-
14
L-isoleucine
-
pH 7.5, 37°C
0.0179
tRNALeu(UUR)
-
-
-
0.0002 - 0.0022
tRNALeuCUN
-
0.0015 - 0.006
tRNALeuUUR
-
additional information
additional information
-
2.04
L-isoleucine
wild-type, pH 7.6, 30°C
3.3
L-isoleucine
mutant D399A, pH 7.6, 30°C
0.024
L-leucine
wild-type, pH 7.6, 30°C
0.9
L-leucine
mutant D399A, pH 7.6, 30°C
0.00074
tRNACAGLeu
pH 7.8, 37°C, recombinant wild-type enzyme
-
0.0017
tRNACAGLeu
pH 7.8, 37°C, recombinant mutant R668A
-
0.09
ATP
recombinant mitochondrial isozyme, pH 7.6, 37°C
0.725
ATP
-
37°C, pH 7.6, leucylation, DELTAChcLeuRS (a C-terminal 89-amino acid truncated enzyme form)
0.773
ATP
-
37°C, pH 7.6, leucylation, full-length enzyme
0.99
ATP
-
recombinant mitochondrial isozyme mutant, 37°C
1.308
ATP
-
37°C, pH 7.6, ATP-diphosphate exchange, full-length enzyme
1.349
ATP
-
37°C, pH 7.6, ATP-diphosphate exchange, DELTAChcLeuRS (a C-terminal 89-amino acid truncated enzyme form)
0.0058
L-leucine
-
37°C, pH 7.6, leucylation, DELTAChcLeuRS (a C-terminal 89-amino acid truncated enzyme form)
0.0075
L-leucine
-
37°C, pH 7.6, leucylation, full-length enzyme
0.01
L-leucine
-
recombinant mitochondrial isozyme mutant, 37°C
0.021
L-leucine
-
recombinant mitochondrial isozyme mutant, 37°C
0.045
L-leucine
recombinant mitochondrial isozyme, pH 7.6, 37°C
0.0456
L-leucine
-
pH 7.6, 37°C, wild-type enzyme
0.05
L-leucine
-
pH 7.6, 37°C, mutant D399A
0.064
L-leucine
-
37°C, pH 7.6, ATP-diphosphate exchange, DELTAChcLeuRS (a C-terminal 89-amino acid truncated enzyme form)
0.075
L-leucine
-
37°C, pH 7.6, ATP-diphosphate exchange, full-length enzyme
0.13
L-leucine
-
pH 7.5, 37°C
0.0014
tRNALeu
-
37°C, pH 7.6, tRNALeu from calf liver, leucylation, DELTAChcLeuRS (a C-terminal 89-amino acid truncated enzyme form)
0.0019
tRNALeu
-
37°C, pH 7.6, tRNALeu from calf liver, leucylation, full-length enzyme
0.014
tRNALeu
recombinant mitochondrial isozyme, pH 7.6, 37°C
0.0002
tRNALeuCUN
-
Escherichia coli derived substrate, pH 7.0, 37°C, recombinant wild-type enzyme
-
0.0018
tRNALeuCUN
-
Escherichia coli derived substrate, pH 7.0, 37°C, recombinant mutants K600L and K600R
-
0.0022
tRNALeuCUN
-
Escherichia coli derived substrate, pH 7.0, 37°C, recombinant mutant K600F
-
0.0015
tRNALeuUUR
-
human derived substrate, pH 7.0, 37°C, recombinant mutant K600L
-
0.004
tRNALeuUUR
-
human derived substrate, pH 7.0, 37°C, recombinant mutant K600R
-
0.004
tRNALeuUUR
-
human derived substrate, pH 7.0, 37°C, recombinant wild-type enzyme
-
0.006
tRNALeuUUR
-
human derived substrate, pH 7.0, 37°C, recombinant mutant K600F
-
additional information
additional information
dissociation constants of LeuRS and mutants from human cytoplasm for their cognate tRNAs
-
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
-
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
-
additional information
additional information
-
turnover numbers for tRNALeu(UUR) variants
-
additional information
additional information
-
kinetic constants of wild-type and D399A mutant of LeuRS in amino acid activation reaction with different amino acids, overview. Cytoplasmic LeuRS overexpressed in Escherichia coli exhibits the same kcat values as the one overexpressed in insect cells using in vitro transcribed tRNA
-
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0.07
L-isoleucine
-
pH 7.5, 37°C
0.003 - 0.14
tRNALeuUUR
-
additional information
additional information
-
turnover numbers for tRNALeu(UUR) variants
-
0.34
L-isoleucine
wild-type, pH 7.6, 30°C
0.51
L-isoleucine
mutant D399A, pH 7.6, 30°C
2.1
L-leucine
wild-type, pH 7.6, 30°C
5.6
L-leucine
mutant D399A, pH 7.6, 30°C
0.56
tRNACAGLeu
pH 7.8, 37°C, recombinant mutant R668A
-
2.6
tRNACAGLeu
pH 7.8, 37°C, recombinant wild-type enzyme
-
0.22
ATP
-
recombinant mitochondrial isozyme mutant, 37°C
0.27
ATP
-
37°C, pH 7.6, leucylation, full-length enzyme
0.55
ATP
-
37°C, pH 7.6, leucylation, DELTAChcLeuRS (a C-terminal 89-amino acid truncated enzyme form)
0.74
ATP
-
37°C, pH 7.6, ATP-diphosphate exchange, DELTAChcLeuRS (a C-terminal 89-amino acid truncated enzyme form)
0.79
ATP
-
37°C, pH 7.6, ATP-diphosphate exchange, full-length enzyme
0.8
ATP
recombinant mitochondrial isozyme, pH 7.6, 37°C
0.18
L-leucine
-
recombinant mitochondrial isozyme mutant, 37°C
0.23
L-leucine
-
recombinant mitochondrial isozyme mutant, 37°C
0.3
L-leucine
-
37°C, pH 7.6, leucylation, full-length enzyme
0.56
L-leucine
-
37°C, pH 7.6, leucylation, DELTAChcLeuRS (a C-terminal 89-amino acid truncated enzyme form)
0.81
L-leucine
-
37°C, pH 7.6, ATP-diphosphate exchange, DELTAChcLeuRS (a C-terminal 89-amino acid truncated enzyme form)
0.82
L-leucine
-
37°C, pH 7.6, ATP-diphosphate exchange, full-length enzyme
2
L-leucine
-
pH 7.5, 37°C
2.7
L-leucine
recombinant mitochondrial isozyme, pH 7.6, 37°C
25.8
L-leucine
-
pH 7.6, 37°C, wild-type enzyme
26.2
L-leucine
-
pH 7.6, 37°C, mutant D399A
0.028
tRNALeu
-
37°C, pH 7.6, tRNALeu from calf liver, leucylation, full-length enzyme
0.059
tRNALeu
-
37°C, pH 7.6, tRNALeu from calf liver, leucylation, DELTAChcLeuRS (a C-terminal 89-amino acid truncated enzyme form)
0.12
tRNALeu
recombinant mitochondrial isozyme, pH 7.6, 37°C
0.35
tRNALeuCUN
-
Escherichia coli derived substrate, pH 7.0, 37°C, recombinant mutant K600L
-
0.39
tRNALeuCUN
-
Escherichia coli derived substrate, pH 7.0, 37°C, recombinant wild-type enzyme
-
3
tRNALeuCUN
-
Escherichia coli derived substrate, pH 7.0, 37°C, recombinant mutant K600F
-
3.2
tRNALeuCUN
-
Escherichia coli derived substrate, pH 7.0, 37°C, recombinant mutant K600R
-
0.003
tRNALeuUUR
-
human derived substrate, pH 7.0, 37°C, recombinant mutant K600L
-
0.09
tRNALeuUUR
-
human derived substrate, pH 7.0, 37°C, recombinant wild-type enzyme
-
0.13
tRNALeuUUR
-
human derived substrate, pH 7.0, 37°C, recombinant mutant K600F
-
0.14
tRNALeuUUR
-
human derived substrate, pH 7.0, 37°C, recombinant mutant K600R
-
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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
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
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
metabolism
LRS-RagD interaction plays a pivotal role in the nutrientdependent mTORC1 signalling pathway
metabolism
mTORC1 lysosomal translocation and activation in response to amino acids requires the GTP-bound form of RagA or B as well as the GDP-bound form of RagC or D. The Ragulator complex and the GATOR1 complex act as GEF (guanine nucleotide exchange factor) and GAP (GTPase activating protein) for RagA/B, respectively. Role of LRS as a leucine sensor upstream of TORC1. Two other tRNA synthetases, IRS (isoleucyl-tRNA synthetase) and EPRS (glutamyl-prolyl-tRNA synthetase), are both in the multi-tRNA synthetase complex together with enzyme LRS, but both have no effect on leucine-stimulated Vps34 activity. LRS directly regulates Vps34 activity
physiological function
aminoacyl-tRNA synthetases (aaRSs) are a large and diverse family of enzymes that catalyze the attachment of amino acids to their cognate tRNAs in a two-step aminoacylation reaction as follows: 1. amino acid activation by ATP hydrolysis to form an aminoacyl-adenylate intermediate, and 2. transfer of the aminoacyl moiety from the intermediate to the cognate tRNA isoacceptor to form aminoacyl-tRNA (aa-tRNA)
physiological function
leucyl-tRNA synthetase (LRS) is a leucine sensor for the activation of Vps34-PLD1 upstream of mTORC1. LRS binds to RagD-GTP, and forms a LRS-RagD complex, which translocates mTORC1 from the cytosol to the lysosome surface for subsequent activation of the mTORC1 signalling pathway. LRS is necessary for amino acid-induced Vps34 activation, cellular phosphatidylinositol-3-phosphate level increase, PLD1 activation, and PLD1 lysosomal translocation. Leucine binding but not tRNA charging activity of LRS is required for this regulation. LRS directly interacts with Vps34 in a non-autophagic complex, and activates Vps34 kinase activity in a leucine-dependent manner. Vps34 and PLD1 are required to mediate LRS activation of mTORC1. Only non-autophagic Vps34 complexes are involved in amino acid signaling to mTOR. LRS is necessary for amino acid activation of PLD1. Overexpression of LRS enhanced amino acid activation of S6K1
physiological function
leucyl-tRNA synthetases (LeuRSs) catalyze the linkage of leucine with tRNALeu
physiological function
the direct interaction between enzyme LRS and RagD activates mTORC1 in live cells under leucine-deprived conditions. The nutrient sensing mechanism of mTORC1, particularly for Leu, an essential biomarker for nutrient status in cellular systems, is regulated by protein-protein interactions between LRS and RagD and directly mediate mTORC1 activation
malfunction
mutations in mitochondrial DNA determine important human diseases. The majority of the known pathogenic mutations are located in transfer RNA (tRNA) genes and are responsible for a wide range of currently untreatable disorders. The detrimental effects of mt-tRNA point mutations can be attenuated by increasing the expression of the cognate mt-aminoacyl-tRNA synthetases (aaRSs). The isolated C-terminal domain of human mt-leucyl-tRNA synthetase (LeuRS-Cterm) localizes to mitochondria and ameliorates the energetic defect in trans-mitochondrial cybrids carrying mutations either in the cognate mt-tRNALeu(UUR) or in the non-cognate mt-tRNAIle gene.Since the mt-LeuRS-Cterm does not possess catalytic activity, its rescuing ability is most likely mediated by a chaperon-like effect, consisting in the stabilization of the tRNA structure altered by the mutation
malfunction
the C-terminal domain of human mt leucyl-tRNA synthetase is both necessary and sufficient to improve the pathologic phenotype associated either with these mild mutations or with the severe m.3243A>G mutation in the mt-tRNALeu(UUR) gene, overview. The small, non-catalytic domain is able to directly and specifically interact in vitro with human mt-tRNALeu(UUR) with high affinity and stability and, with lower affinity, with mt-tRNAIle. The carboxyterminal domain of human mt leucyl-tRNA synthetase can be used to correct mt dysfunctions caused by mt-tRNA mutations. The Cterm domain of human mt-LeuRS directly interacts with mt-tRNALeu(UUR) and mt-tRNAIle in vitro
physiological function
-
the A3243G mutation of the tRNALeu gene causes mitochondrial encephalomyopathy, lactic acidosis, and stroke-like symptoms and 2% of cases of type 2 diabetes. The alteration of aminoacylation of tRNALeu(UUR) caused by the A3243G mutation leads to mitochondrial translational defects and thereby reduces the aminoacylating efficiencies of tRNALeu(UUR) as well as of tRNAAla and tRNAMet
physiological function
-
aminoacyl-tRNA synthetases have evolved editing mechanisms to hydrolyze misactivated amino acids (pre-transfer editing) or misacylated tRNAs (post-transfer editing). Class Ia leucyl-tRNA synthetase may misactivate various natural and non-protein amino acids and then mischarge tRNALeu. The fidelity of prokaryotic LeuRS depends on multiple editing pathways to clear the incorrect intermediates and products in every step of aminoacylation reaction. Post-transfer editing as a final checkpoint of the reaction is very important to prevent mis-incorporation in vitro
physiological function
-
the carboxy-terminal domain of human mitochondrial leucyl-tRNA synthetase can be used to correct mitochondrial dysfunctions caused by mitochondrial tRNA mutations like the phenotype of m.3243A>G MTTL1 mutant cybrids
physiological function
-
the enzyme is a leucine sensor for serine/threonine kinase TORC1 and interacts with Gtr2
physiological function
-
the enzyme plays a critical role in amino acid-induced mammalian target of rapamycin C1 activation by sensing intracellular leucine concentration and initiating molecular events leading to mammalian target of rapamycin C1 activation. The enzyme directly binds to Rag GTPase, the mediator of amino acid signaling to mTORC1, in an amino acid-dependent manner and functions as a GTPase-activating protein for Rag GTPase to activate mammalian target of rapamycin C1
physiological function
-
leucyl-tRNA synthetase (LRS) plays major roles in providing leucine-tRNA and activating mechanistic target of rapamycin complex 1 (mTORC1) through intracellular leucine sensing. mTORC1 activated by amino acids affects the influence on physiology functions including cell proliferation, protein synthesis and autophagy in various organisms. Crosstalk between leucine sensing, LRS translocation, RagD interaction, and mTORC1 activation, mTORC1 activation is related to LRS translocation dependent on leucine, analysis of relationship between mTORC1 activation and LRS translocation, overview
additional information
small-molecule protein-protein interactions modulators between LRS and RagD can be used as powerful research tools for studying the nutrient-dependent activation of mTORC1 and the subsequent biological outcome
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
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
additional information
-
human leucyl-tRNA synthetase and mitochondrial protein elongation factor EF-Tu show suppressing cross-activity on different tRNA mutants in humans and Saccharomyces cerevisiae, mechanism and specificity of suppression, overview. Suppressive activities of wild-type and mutant enzymes, overview
additional information
analysis of the bacterial LeuRS structures (PDB IDs 2BTE and 4AS1) reveals that the isolated C-terminal domain of human mt-leucyl-tRNA synthetase (LeuRS-Cterm) interacts with the elbow region of the cognate tRNA and establishes a higher number of contacts with the sugar-phosphate backbone than with nucleotide-specific chemical groups, preferred interaction of human mt-LeuRS-Cterm with ribose and phosphate oxygen atoms
additional information
-
analysis of the bacterial LeuRS structures (PDB IDs 2BTE and 4AS1) reveals that the isolated C-terminal domain of human mt-leucyl-tRNA synthetase (LeuRS-Cterm) interacts with the elbow region of the cognate tRNA and establishes a higher number of contacts with the sugar-phosphate backbone than with nucleotide-specific chemical groups, preferred interaction of human mt-LeuRS-Cterm with ribose and phosphate oxygen atoms
additional information
three human mitochondrial aminoacyl-tRNA syntethases, namely leucyl-, valyl-, and isoleucyl-tRNA synthetase are able to improve both viability and bioenergetic proficiency of human transmitochondrial cybrid cells carrying pathogenic mutations in the mt-tRNAIle gene
additional information
-
three human mitochondrial aminoacyl-tRNA syntethases, namely leucyl-, valyl-, and isoleucyl-tRNA synthetase are able to improve both viability and bioenergetic proficiency of human transmitochondrial cybrid cells carrying pathogenic mutations in the mt-tRNAIle gene
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A525S
site-directed mutagenesis, the mutant shows altered kinetics and reduced catalytic efficiency in the aminoacylation reaction compared to the wild-type enzyme
C527E
site-directed mutagenesis, the mutant shows altered kinetics and reduced catalytic efficiency in the aminoacylation reaction compared to the wild-type enzyme
D250A
site-directed mutagenesis, the mutant shows altered kinetics and reduced catalytic efficiency in the aminoacylation reaction compared to the wild-type enzyme
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
D250N
site-directed mutagenesis, the mutant shows altered kinetics and reduced catalytic efficiency in the aminoacylation reaction compared to the wild-type enzyme
D250R
site-directed mutagenesis, inactive mutant
D252R
site-directed mutagenesis, inactive mutant
D399A
40fold increase in Km for leucine activation. Mutation eliminates Ile-tRNALeu deacylation activity
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
F50A/Y52A
site-directed mutagenesis, the leucine-binding deficient LRS mutant also activates Vps34, but to a lesser degree and in a leucine-independent manner
G245A
site-directed mutagenesis, the mutant shows altered kinetics and reduced catalytic efficiency in the aminoacylation reaction compared to the wild-type enzyme
G245D
site-directed mutagenesis, the mutant shows altered kinetics and 50% reduced catalytic efficiency in the aminoacylation reaction compared to the wild-type enzyme
G245P
site-directed mutagenesis, inactive mutant
G245R
site-directed mutagenesis, the mutant shows altered kinetics and 50% reduced catalytic efficiency in the aminoacylation reaction compared to the wild-type enzyme
H251D
site-directed mutagenesis, inactive mutant
P242E
site-directed mutagenesis, the mutant shows altered kinetics and reduced catalytic efficiency in the aminoacylation reaction compared to the wild-type enzyme
P247A
site-directed mutagenesis, the mutant shows altered kinetics and reduced catalytic efficiency in the aminoacylation reaction compared to the wild-type enzyme
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
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
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
R766A
site-directed mutagenesis, the mutation decreases the kcat/Km value to less than 10% that of the wild-type enzyme hcLeuRS
S519G
site-directed mutagenesis, the mutant shows altered kinetics and reduced catalytic efficiency in the aminoacylation reaction compared to the wild-type enzyme
T298A
activity similar to wild-type, mutation maintains Ile-tRNALeu deacylation activity
T298Y
mutation uncouples specificity in the editing active site and mutant hydrolyzes Leu-tRNALeu
V523I
site-directed mutagenesis, the mutant shows altered kinetics and reduced catalytic efficiency in the aminoacylation reaction compared to the wild-type enzyme
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
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
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
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
A3243G
-
respiratory chain defects in A3243G mutant cells is suppressed by overexpressing human mitochondrial leucyl-tRNA synthetase. The rates of oxygen consumption in suppressed cells are directly proportional to the levels of leucyl-tRNA synthetase. 15fold higher levels of leucyl-tRNA synthetase results in wild-type respiratory chain function. The suppressed cells have increased steady-state levels of tRNA(Leu(UUR)) and up to 3fold higher steady-state levels of mitochondrial translation products, but do not have rates of protein synthesis above those in parental mutant cells
D399A
-
site-directed mutagenesis, tRNA selectivity compared to the wild-type enzyme
D399K
-
mutant is resitant to inhibitor 5-fluoro-2,1-benzoxaborol-1(3H)-ol but more sensitive to norvaline inhibition
K600F
-
the mutation leads to altered catalytic efficiency and perturbations to the discrimination of leucine and isoleucine and affects tRNA recognition and aminoacylation, the mutant demonstrates a 9fold decrease in its ability to distinguish between leucine and isoleucine effectively, the activity is reduced compared to the wild-type enzyme
K600L
-
the mutation leads to altered catalytic efficiency and perturbations to the discrimination of leucine and isoleucine and affects tRNA recognition and aminoacylation, the mutant demonstrates an 11fold increase in its ability to distinguish between leucine and isoleucine effectively, the activity is reduced compared to the wild-type enzyme
K600R
-
the mutation leads to altered catalytic efficiency and perturbations to the discrimination of leucine and isoleucine and affects tRNA recognition and aminoacylation, the mutant shows a slight decrease in activity compared to the wild-type enzyme
additional information
enzyme knockout by shRNA and iRNA
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
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
additional information
-
to explore the oncogenic potential of LARS1 over-expression in lung cancer, LARS1 is knocked-down using siRNA. LARS1 knock-down cells show reduced ability to migrate through transwell membrane and to form colonies in both soft agar and culture plate
additional information
generation of the isolated C-terminal domain of human mt leucyl-tRNA synthetase, and of DELTACterm mutant
additional information
-
generation of the isolated C-terminal domain of human mt leucyl-tRNA synthetase, and of DELTACterm mutant
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Bullard, J.M.; Cai, Y.C.; Spremulli, L.L.
Expression and characterization of the human mitochondrial leucyl-tRNA synthetase
Biochim. Biophys. Acta
1490
245-258
2000
Homo sapiens (Q15031), Homo sapiens
brenda
Yao, Y.N.; Wang, L.; Wu, X.F.; Wang, E.D.
Human mitochondrial leucyl-tRNA synthetase with high activity produced from Escherichia coli
Protein Expr. Purif.
30
112-116
2003
Homo sapiens
brenda
Lue, S.W.; Kelley, S.O.
An aminoacyl-tRNA synthetase with a defunct editing site
Biochemistry
44
3010-3016
2005
Escherichia coli, Homo sapiens
brenda
Ling, C.; Yao, Y.N.; Zheng, Y.G.; Wei, H.; Wang, L.; Wu, X.F.; Wang, E.D.
The C-terminal appended domain of human cytosolic leucyl-tRNA synthetase is indispensable in its interaction with arginyl-tRNA synthetase in the multi-tRNA synthetase complex
J. Biol. Chem.
280
34755-34763
2005
Homo sapiens
brenda
Sohm, B.; Sissler, M.; Park, H.; King, M.P.; Florentz, C.
Recognition of human mitochondrial tRNALeu(UUR) by its cognate leucyl-tRNA synthetase
J. Mol. Biol.
339
17-29
2004
Homo sapiens
brenda
Lue, S.W.; Kelley, S.O.
A single residue in leucyl-tRNA synthetase affecting amino acid specificity and tRNA aminoacylation
Biochemistry
46
4466-4472
2007
Escherichia coli, Homo sapiens
brenda
Shin, S.H.; Kim, H.S.; Jung, S.H.; Xu, H.D.; Jeong, Y.B.; Chung, Y.J.
Implication of leucyl-tRNA synthetase 1 (LARS1) over-expression in growth and migration of lung cancer cells detected by siRNA targeted knock-down analysis
Exp. Mol. Med.
40
229-236
2008
Homo sapiens
brenda
Yao, P.; Zhou, X.L.; He, R.; Xue, M.Q.; Zheng, Y.G.; Wang, Y.F.; Wang, E.D.
Unique residues crucial for optimal editing in yeast cytoplasmic Leucyl-tRNA synthetase are revealed by using a novel knockout yeast strain
J. Biol. Chem.
283
22591-22600
2008
Homo sapiens, Saccharomyces cerevisiae (P26637), Saccharomyces cerevisiae
brenda
Park, H.; Davidson, E.; King, M.P.
Overexpressed mitochondrial leucyl-tRNA synthetase suppresses the A3243G mutation in the mitochondrial tRNA(Leu(UUR)) gene
RNA
14
2407-2416
2008
Homo sapiens
brenda
Pang, Y.L.; Martinis, S.A.
A paradigm shift for the amino acid editing mechanism of human cytoplasmic leucyl-tRNA synthetase
Biochemistry
48
8958-8964
2009
Homo sapiens (Q9P2J5), Homo sapiens
brenda
Seiradake, E.; Mao, W.; Hernandez, V.; Baker, S.J.; Plattner, J.J.; Alley, M.R.; Cusack, S.
Crystal structures of the human and fungal cytosolic Leucyl-tRNA synthetase editing domains: A structural basis for the rational design of antifungal benzoxaboroles
J. Mol. Biol.
390
196-207
2009
Candida albicans, Homo sapiens
brenda
Li, R.; Guan, M.X.
Human mitochondrial leucyl-tRNA synthetase corrects mitochondrial dysfunctions due to the tRNALeu(UUR) A3243G mutation, associated with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like symptoms and diabetes
Mol. Cell. Biol.
30
2147-2154
2010
Homo sapiens
brenda
Montanari, A.; De Luca, C.; Frontali, L.; Francisci, S.
Aminoacyl-tRNA synthetases are multivalent suppressors of defects due to human equivalent mutations in yeast mt tRNA genes
Biochim. Biophys. Acta
1803
1050-1057
2010
Homo sapiens
brenda
Chen, X.; Ma, J.J.; Tan, M.; Yao, P.; Hu, Q.H.; Eriani, G.; Wang, E.D.
Modular pathways for editing non-cognate amino acids by human cytoplasmic leucyl-tRNA synthetase
Nucleic Acids Res.
39
235-247
2011
Homo sapiens
brenda
Duran, R.V.; Hall, M.N.
Leucyl-tRNA synthetase: double duty in amino acid sensing
Cell Res.
22
1207-1209
2012
Saccharomyces cerevisiae, Homo sapiens
brenda
Han, J.M.; Jeong, S.J.; Park, M.C.; Kim, G.; Kwon, N.H.; Kim, H.K.; Ha, S.H.; Ryu, S.H.; Kim, S.
Leucyl-tRNA synthetase is an intracellular leucine sensor for the mTORC1-signaling pathway
Cell
149
410-424
2012
Homo sapiens
brenda
Perli, E.; Giordano, C.; Pisano, A.; Montanari, A.; Campese, A.F.; Reyes, A.; Ghezzi, D.; Nasca, A.; Tuppen, H.A.; Orlandi, M.; Di Micco, P.; Poser, E.; Taylor, R.W.; Colotti, G.; Francisci, S.; Morea, V.; Frontali, L.; Zeviani, M.; dAmati, G.
The isolated carboxy-terminal domain of human mitochondrial leucyl-tRNA synthetase rescues the pathological phenotype of mitochondrial tRNA mutations in human cells
EMBO Mol. Med.
6
169-182
2014
Homo sapiens
brenda
Choi, H.; Son, J.B.; Kang, J.; Kwon, J.; Kim, J.H.; Jung, M.; Kim, S.K.; Kim, S.; Mun, J.Y.
Leucine-induced localization of Leucyl-tRNA synthetase in lysosome membrane
Biochem. Biophys. Res. Commun.
493
1129-1135
2017
Homo sapiens
brenda
Yoon, M.S.; Son, K.; Arauz, E.; Han, J.M.; Kim, S.; Chen, J.
Leucyl-tRNA synthetase activates Vps34 in amino acid-sensing mTORC1 signaling
Cell Rep.
16
1510-1517
2016
Homo sapiens (Q9P2J5)
brenda
Kim, C.; Jung, J.; Tung, T.T.; Park, S.B.
beta-Turn mimetic-based stabilizers of protein-protein interactions for the study of the non-canonical roles of leucyl-tRNA synthetase
Chem. Sci.
7
2753-2761
2016
Homo sapiens (Q9P2J5)
brenda
Perli, E.; Giordano, C.; Pisano, A.; Montanari, A.; Campese, A.F.; Reyes, A.; Ghezzi, D.; Nasca, A.; Tuppen, H.A.; Orlandi, M.; Di Micco, P.; Poser, E.; Taylor, R.W.; Colotti, G.; Francisci, S.; Morea, V.; Frontali, L.; Zeviani, M.; dAmati, G.
The isolated carboxy-terminal domain of human mitochondrial leucyl-tRNA synthetase rescues the pathological phenotype of mitochondrial tRNA mutations in human cells
EMBO Mol. Med.
6
169-182
2014
Homo sapiens (Q15031), Homo sapiens
brenda
Giordano, C.; Morea, V.; Perli, E.; dAmati, G.
The phenotypic expression of mitochondrial tRNA-mutations can be modulated by either mitochondrial leucyl-tRNA synthetase or the C-terminal domain thereof
Front. Genet.
6
113
2015
Homo sapiens (Q15031), Homo sapiens
brenda
Yan, W.; Ye, Q.; Tan, M.; Chen, X.; Eriani, G.; Wang, E.D.
Modulation of aminoacylation and editing properties of leucyl-tRNA synthetase by a conserved structural module
J. Biol. Chem.
290
12256-12267
2015
Pyrococcus horikoshii (O58698), Aquifex aeolicus (O66680 AND O67646), Escherichia coli (P07813), Escherichia coli, Mesomycoplasma mobile (Q6KHA5), Homo sapiens (Q9P2J5), Mesomycoplasma mobile ATCC 43663 / 163K / NCTC 11711 (Q6KHA5), Pyrococcus horikoshii ATCC 700860 / DSM 12428 / JCM 9974 / NBRC 100139 / OT-3 (O58698)
brenda
Gudzera, O.I.; Golub, A.G.; Bdzhola, V.G.; Volynets, G.P.; Kovalenko, O.P.; Boyarshin, K.S.; Yaremchuk, A.D.; Protopopov, M.V.; Yarmoluk, S.M.; Tukalo, M.A.
Identification of Mycobacterium tuberculosis leucyl-tRNA synthetase (LeuRS) inhibitors among the derivatives of 5-phenylamino-2H-[1,2,4]triazin-3-one
J. Enzyme Inhib. Med. Chem.
31
201-207
2016
Mycobacterium tuberculosis (P9WFV1), Mycobacterium tuberculosis, Homo sapiens (Q9P2J5), Homo sapiens, Mycobacterium tuberculosis ATCC 25618 / H37Rv (P9WFV1)
brenda
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
RNA
20
1440-1450
2014
Homo sapiens (Q9P2J5), Homo sapiens
brenda