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ATP + L-methionine + tRNAMet
AMP + diphosphate + L-methionyl-tRNAMet
ATP + L-methionine + tRNAMet
AMP + diphosphate + L-methionyl-tRNAMet
additional information
?
-
ATP + L-methionine + tRNAMet
AMP + diphosphate + L-methionyl-tRNAMet
-
-
-
?
ATP + L-methionine + tRNAMet
AMP + diphosphate + L-methionyl-tRNAMet
-
-
-
r
ATP + L-methionine + tRNAMet
AMP + diphosphate + L-methionyl-tRNAMet
human mitochondrial wild-type and mutant mtRNAs: T5048 deletion, and T5052C or T5012A point mutations, initiator tRNA from Escherichia coli, tRNAMet from Bos taurus
-
-
r
ATP + L-methionine + tRNAMet
AMP + diphosphate + L-methionyl-tRNAMet
-
-
-
?
ATP + L-methionine + tRNAMet
AMP + diphosphate + L-methionyl-tRNAMet
-
-
-
?
ATP + L-methionine + tRNAMet
AMP + diphosphate + L-methionyl-tRNAMet
-
-
-
-
?
ATP + L-methionine + tRNAMet
AMP + diphosphate + L-methionyl-tRNAMet
-
-
-
r
ATP + L-methionine + tRNAMet
AMP + diphosphate + L-methionyl-tRNAMet
-
the C-terminal ancillary RNA-binding domain is important for activity and has dual function provided by 2 structural motifs: 1. the helix-turn-helix HTH motif, which confers rate-limiting dissociation of the aminoaclyted tRNA from the enzyme, and 2. the KGKKKK lysine-rich cluster LRC, which is probably involved in accelerating the association step of deacylated tRNA
-
r
ATP + L-methionine + tRNAMet
AMP + diphosphate + L-methionyl-tRNAMet
-
the nucleolar located enzyme is related to rRNA synthesis, the cytoplasmic enzyme is involved in protein biosynthesis
-
?
additional information
?
-
the enzyme performs ATP/diphosphate exchange in absence of substrates
-
-
?
additional information
?
-
-
the enzyme performs ATP/diphosphate exchange in absence of substrates
-
-
?
additional information
?
-
-
homocysteine thiolactone is formed as a product of an error-editing reaction, which prevents incorporation of homocysteine into tRNA and protein (not enzyme from temperature-sensitive mutant of CHO-cells, at non-permissive temperature)
-
-
?
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2-(1H-indol-3-yl)-1,4-dihydro-2H-3,1-benzoxazine
-
-
2-(1H-indol-3-yl)-5-(4-methoxyphenyl)-1-oxa-3-azaspiro[5.5]undecane
-
-
2-(2,3-dihydroquinolin-2-yl)phenol
-
-
2-(2,4-dichlorophenyl)-6-methylquinoline
-
-
2-(2,4-dichlorophenyl)quinoline
-
-
2-(2,6-difluorophenyl)-5-(4-methoxyphenyl)-1-oxa-3-azaspiro[5.5]undecane
-
-
2-(2-bromophenyl)-6-methyl-2,3-dihydroquinoline
-
-
2-(2-butyl-4-chloro-1-(4-nitrobenzyl)-1H-imidazol-5-yl)-2,4-dihydro-1Hbenzo[d][1,3]oxazine
-
-
2-(2-butyl-4-chloro-1-(4-phenoxybenzyl)-1H-imidazol-5-yl)-5-(4-methoxyphenyl)-1-oxa-3-azaspiro[5.5]undecane
-
-
2-(2-butyl-4-chloro-1H-imidazol-5-yl)-1,4-dihydro-2H-3,1-benzoxazine
-
-
2-(2-butyl-4-chloro-1H-imidazol-5-yl)-5-(4-methoxyphenyl)-1-oxa-3-azaspiro[5.5]undecane
-
-
2-(4-bromophenyl)-5-(4-methoxyphenyl)-1-oxa-3-azaspiro[5.5]undecane
-
-
3-(1,4-dihydro-2H-3,1-benzoxazin-2-yl)-4H-1-benzopyran-4-one
-
-
3-(5-(4-methoxyphenyl)-1-oxa-3-azaspiro[5.5]undecan-2-yl)-4H-chromen-4-one
-
-
3-(6-chloro-1,4-dihydro-2H-3,1-benzoxazin-2-yl)-4H-1-benzopyran-4-one
-
-
3-(6-methyl-1,4-dihydro-2H-3,1-benzoxazin-2-yl)-4H-1-benzopyran-4-one
-
-
4'-((2-butyl-4-chloro-5-(5-(4-methoxyphenyl)-1-oxa-3-azaspiro[5.5]undecan-2-yl)-1H-imidazol-1-yl)methyl)-[1,1'-biphenyl]-2-carbonitrile
-
-
4'-[(3-[5-[4-(hydroxymethyl)phenyl]-1-oxa-3-azaspiro[5.5]undecan-2-yl]-2,3-dihydro-1H-indol-1-yl)methyl][1,1'-biphenyl]-2-carbonitrile
-
-
4'-[[3-(1,4-dihydro-2H-3,1-benzoxazin-2-yl)-1H-indol-1-yl]methyl][1,1'-biphenyl]-2-carbonitrile
-
-
4-(1,4-dihydro-2H-3,1-benzoxazin-2-yl)phenol
-
-
4-(5-(4-methoxyphenyl)-1-oxa-3-azaspiro[5.5]undecan-2-yl)-N,Ndimethylaniline
-
-
4-(6-chloroquinolin-2-yl)aniline
-
-
4-(7-chloro-1,4-dihydro-2H-3,1-benzoxazin-2-yl)phenol
-
-
5-(4-methoxyphenyl)-2-(2-methyl-1H-indol-3-yl)-1-oxa-3-azaspiro[5.5]undecane
-
-
5-(4-methoxyphenyl)-2-(2-phenyl-1H-indol-3-yl)-1-oxa-3-azaspiro[5.5]undecane
-
-
6-chloro-2-(1H-indol-3-yl)-1,4-dihydro-2H-3,1-benzoxazine
-
-
6-chloro-2-(2-phenyl-1H-indol-3-yl)-1,4-dihydro-2H-3,1-benzoxazine
-
-
6-methyl-2-(2-methyl-1H-indol-3-yl)-1,4-dihydro-2H-3,1-benzoxazine
-
-
6-methyl-2-(2-phenyl-1H-indol-3-yl)-1,4-dihydro-2H-3,1-benzoxazine
-
-
actinomycin D
-
inhibits the nucleolar located enzyme due to dependence on polymerase I
alpha-Amanitin
-
inhibits the nucleolar located enzyme due to dependence on polymerase I
cisplatin
-
inhibits the nucleolar located enzyme due to dependence on polymerase I
RNase
-
inhibits the nucleolar located enzyme due to dependence on rRNA
-
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Anemia
Mutations in methionyl-tRNA synthetase gene in a Chinese family with interstitial lung and liver disease, postnatal growth failure and anemia.
Anthrax
Horizontal transfer of drug-resistant aminoacyl-transfer-RNA synthetases of anthrax and Gram-positive pathogens.
Ataxia
Mutations in the mitochondrial methionyl-tRNA synthetase cause a neurodegenerative phenotype in flies and a recessive ataxia (ARSAL) in humans.
Atherosclerosis
[Paraoxonase: its multiple functions and pharmacological regulation].
Bile Duct Neoplasms
New staining method using methionyl-tRNA synthetase 1 antibody for brushing cytology of bile duct cancer.
Breast Neoplasms
High methionyl-tRNA synthetase expression predicts poor prognosis in patients with breast cancer.
Brucellosis
Brucella melitensis Methionyl-tRNA-Synthetase (MetRS), a Potential Drug Target for Brucellosis.
Brucellosis
Correction: Brucella melitensis Methionyl-tRNA-Synthetase (MetRS), a Potential Drug Target for Brucellosis.
Brucellosis
High Throughput Virtual Screening to Identify Novel natural product Inhibitors for MethionyltRNA-Synthetase of Brucella melitensis.
Carcinoma
Cloning of a human cDNA encoding a protein with high homology to yeast methionyl-tRNA synthetase.
Carcinoma, Non-Small-Cell Lung
Methionyl-tRNA Synthetase is a Useful Diagnostic Marker for Lymph Node Metastasis in Non-Small Cell Lung Cancer.
Carcinoma, Non-Small-Cell Lung
Methionyl-tRNA synthetase overexpression is associated with poor clinical outcomes in non-small cell lung cancer.
Chronic Limb-Threatening Ischemia
Deciphering the in vivo Dynamic Proteomics of Mesenchymal Stem Cells in Critical Limb Ischemia.
Clostridium Infections
Inhibitory effect of REP3123 on toxin and spore formation in Clostridium difficile, and in vivo efficacy in a hamster gastrointestinal infection model.
Clostridium Infections
Spectrum of activity and mode of action of REP3123, a new antibiotic to treat Clostridium difficile infections.
Decompression Sickness
Topographic modeling of free and methionyl-tRNA synthetase bound tRNAfMet by singlet-singlet energy transfer: bending of the 3'-terminal arm in tRNAfMet.
Gram-Positive Bacterial Infections
Development of methionyl-tRNA synthetase inhibitors as antibiotics for Gram-positive bacterial infections.
Heart Defects, Congenital
Inhibiting MARSs reduces hyperhomocysteinemia-associated neural tube and congenital heart defects.
Infections
Induced resistance to methionyl-tRNA synthetase inhibitors in Trypanosoma brucei is due to overexpression of the target.
Infections
Inhibitory effect of REP3123 on toxin and spore formation in Clostridium difficile, and in vivo efficacy in a hamster gastrointestinal infection model.
Infections
Methionyl-tRNA synthetase inhibitor has potent in vivo activity in a novel Giardia lamblia luciferase murine infection model.
Infections
Selective inhibitors of methionyl-tRNA synthetase have potent activity on Trypanosoma brucei infection in mice.
Infections
Spectrum of activity and mode of action of REP3123, a new antibiotic to treat Clostridium difficile infections.
Liver Diseases
Mutations in methionyl-tRNA synthetase gene in a Chinese family with interstitial lung and liver disease, postnatal growth failure and anemia.
Liver Diseases
Novel methionyl-tRNA synthetase gene variants/phenotypes in interstitial lung and liver disease: A case report and review of literature.
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.
Lung Neoplasms
Methionyl-tRNA synthetase and aminoacyl-tRNA synthetases interacting multi-functional protein-lacking exon 2 as potential diagnostic biomarkers for lung cancer.
Lung Neoplasms
Methionyl-tRNA Synthetase is a Useful Diagnostic Marker for Lymph Node Metastasis in Non-Small Cell Lung Cancer.
Lung Neoplasms
Methionyl-tRNA synthetase overexpression is associated with poor clinical outcomes in non-small cell lung cancer.
Lymphatic Metastasis
Methionyl-tRNA Synthetase is a Useful Diagnostic Marker for Lymph Node Metastasis in Non-Small Cell Lung Cancer.
Metabolic Syndrome
A 3-SNP gene risk score and a metabolic risk score both predict hypertriglyceridemia and cardiovascular disease risk.
Myocardial Infarction
Urinary excretion of homocysteine thiolactone and the risk of acute myocardial infarction in coronary artery disease patients: the WENBIT trial.
Neoplasm Metastasis
Methionyl-tRNA Synthetase is a Useful Diagnostic Marker for Lymph Node Metastasis in Non-Small Cell Lung Cancer.
Neoplasms
Determination of three-dimensional structure and residues of the novel tumor suppressor AIMP3/p18 required for the interaction with ATM.
Neoplasms
Dual role of methionyl-tRNA synthetase in the regulation of translation and tumor suppressor activity of aminoacyl-tRNA synthetase-interacting multifunctional protein-3.
Neoplasms
Increased Mars2 expression upon microRNA-4661-5p-mediated KDM5D downregulation is correlated with malignant degree of gastric cancer cells.
Neoplasms
Methionyl-tRNA synthetase overexpression is associated with poor clinical outcomes in non-small cell lung cancer.
Neoplasms
New staining method using methionyl-tRNA synthetase 1 antibody for brushing cytology of bile duct cancer.
Neoplasms
Screening of quinoline, 1,3-benzoxazine, and 1,3-oxazine-based small molecules against isolated methionyl-tRNA synthetase and A549 and HCT116 cancer cells including an in silico binding mode analysis.
Neoplasms
Stabilization of Cyclin-Dependent Kinase 4 by Methionyl-tRNA Synthetase in p16INK4a-Negative Cancer.
Neural Tube Defects
Inhibiting MARSs reduces hyperhomocysteinemia-associated neural tube and congenital heart defects.
Osteosarcoma
Nuclear localization of aminoacyl-tRNA synthetases using single-cell capillary electrophoresis laser-induced fluorescence analysis.
Parasitic Diseases
Screening of quinoline, 1,3-benzoxazine, and 1,3-oxazine-based small molecules against isolated methionyl-tRNA synthetase and A549 and HCT116 cancer cells including an in silico binding mode analysis.
Pulmonary Alveolar Proteinosis
Biallelic Mutations of Methionyl-tRNA Synthetase Cause a Specific Type of Pulmonary Alveolar Proteinosis Prevalent on Réunion Island.
Pulmonary Alveolar Proteinosis
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.
Pulmonary Alveolar Proteinosis
Methionyl-tRNA synthetase novel mutation causes pulmonary alveolar proteinosis.
Pulmonary Alveolar Proteinosis
Mutations in MARS identified in a specific type of pulmonary alveolar proteinosis alter methionyl-tRNA synthetase activity.
Starvation
Control of cell division in Saccharomyces cerevisiae by methionyl-tRNA.
Trypanosomiasis, African
Distinct States of Methionyl-tRNA Synthetase Indicate Inhibitor Binding by Conformational Selection.
Trypanosomiasis, African
Urea-Based Inhibitors of Trypanosoma brucei Methionyl-tRNA Synthetase: Selectivity and in Vivo Characterization.
Tuberculosis
Biochemical and phylogenetic analyses of methionyl-tRNA synthetase isolated from a pathogenic microorganism, Mycobacterium tuberculosis.
Tuberculosis
Convergent evolution of two different random RNAs for specific interaction with methionyl-tRNA synthetase.
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
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
Structural characterization of free-state and product-state Mycobacterium tuberculosis methionyl-tRNA synthetase reveals an induced-fit ligand-recognition mechanism.
Tuberculosis
The crystal structure of the drug target Mycobacterium tuberculosis methionyl-tRNA synthetase in complex with a catalytic intermediate.
Vascular Diseases
Mutations in methylenetetrahydrofolate reductase or cystathionine beta-synthase gene, or a high-methionine diet, increase homocysteine thiolactone levels in humans and mice.
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0.085
ATP
pH 8.2, 37°C, recombinant enzyme
0.018
L-methionine
pH 8.2, 37°C, recombinant enzyme
additional information
additional information
-
dissociation constants for wild-type and mutant enzymes
-
0.00015
tRNAMet
pH 8.2, 37°C, mitochondrial tRNAMet from Bos taurus, recombinant enzyme
0.00016
tRNAMet
pH 8.2, 37°C, human mitochondrial wild-type tRNAMet, recombinant enzyme
0.0021
tRNAMet
pH 8.2, 37°C, initiator tRNA from Escherichia coli, recombinant enzyme
0.0022
tRNAMet
-
C-terminal extension, pH 7.5, 25°C
0.0033
tRNAMet
-
mutant K863A, pH 7.5, 25°C
0.0035
tRNAMet
-
wild-type enzyme, pH 7.5, 25°C
0.0039
tRNAMet
-
wild-type enzyme in the multi-enzyme complex and mutant K866A, pH 7.5, 25°C
0.0057
tRNAMet
-
mutant R857A, pH 7.5, 25°C
0.0163
tRNAMet
-
mutant K880A, pH 7.5, 25°C
0.0172
tRNAMet
-
mutant K860A, pH 7.5, 25°C
0.032
tRNAMet
-
catalytic domain, pH 7.5, 25°C
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0.033
ATP
pH 8.2, 37°C, recombinant enzyme
0.41
L-methionine
pH 8.2, 37°C, recombinant enzyme
0.019
tRNAMet
pH 8.2, 37°C, mitochondrial tRNAMet from Bos taurus, recombinant enzyme
0.021
tRNAMet
pH 8.2, 37°C, human mitochondrial wild-type tRNAMet, recombinant enzyme
11
tRNAMet
pH 8.2, 37°C, initiator tRNA from Escherichia coli, recombinant enzyme
0.09
tRNAMet
-
C-terminal extension, pH 7.5, 25°C
0.15
tRNAMet
-
wild-type enzyme, pH 7.5, 25°C
0.22
tRNAMet
-
mutant K863A, pH 7.5, 25°C
0.23
tRNAMet
-
mutant K866A, pH 7.5, 25°C
0.46
tRNAMet
-
wild-type enzyme in the multi-enzyme complex, pH 7.5, 25°C
0.47
tRNAMet
-
mutant R857A, pH 7.5, 25°C
0.85
tRNAMet
-
mutant K860A, pH 7.5, 25°C
1.03
tRNAMet
-
mutant K880A, pH 7.5, 25°C
2.4
tRNAMet
-
catalytic domain, pH 7.5, 25°C
6.08
tRNAMet
-
mutant K880A, pH 7.5, 25°C
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Jakubowski, H.; Goldman, E.
Synthesis of homocysteine thiolactone by methionyl-tRNA synthetase in cultured mammalian cells
FEBS Lett.
317
237-240
1993
Saccharomyces cerevisiae, Cricetulus griseus, Escherichia coli, Homo sapiens, Mus musculus
brenda
Kaminska, M.; Shalak, V.; Mirande, M.
The appended C-domain of human methionyl-tRNA synthetase has a tRNA-sequestering function
Biochemistry
40
14309-14316
2001
Homo sapiens
brenda
Ko, Y.G.; Kang, Y.S.; Kim, E.K.; Park, S.G.; Kim, S.
Nucleolar localization of human methionyl-tRNA synthetase and its role in ribosomal RNA synthesis
J. Cell Biol.
149
567-574
2000
Homo sapiens
brenda
Spencer, A.C.; Heck, A.; Takeuchi, N.; Watanabe, K.; Spremulli, L.L.
Characterization of the human mitochondrial methionyl-tRNA synthetase
Biochemistry
43
9743-9754
2004
Homo sapiens (P56192), Homo sapiens
brenda
Green, L.; Bullard, J.; Ribble, W.; Dean, F.; Ayers, D.; Ochsner, U.; Janjic, N.; Jarvis, T.
Inhibition of methionyl-tRNA synthetase by REP8839 and effects of resistance mutations on enzyme activity
Antimicrob. Agents Chemother.
53
86-94
2009
Streptococcus pneumoniae, Escherichia coli, Haemophilus influenzae, Homo sapiens, Staphylococcus aureus
brenda
Critchley, I.A.; Green, L.S.; Young, C.L.; Bullard, J.M.; Evans, R.J.; Price, M.; Jarvis, T.C.; Guiles, J.W.; Janjic, N.; Ochsner, U.A.
Spectrum of activity and mode of action of REP3123, a new antibiotic to treat Clostridium difficile infections
J. Antimicrob. Chemother.
63
954-963
2009
Clostridioides difficile, Streptococcus pneumoniae, Escherichia coli, Haemophilus influenzae, Homo sapiens, Staphylococcus aureus
brenda
van Meel, E.; Wegner, D.J.; Cliften, P.; Willing, M.C.; White, F.V.; Kornfeld, S.; Cole, F.S.
Rare recessive loss-of-function methionyl-tRNA synthetase mutations presenting as a multi-organ phenotype
BMC Med. Genet.
14
106
2013
Homo sapiens (P56192)
brenda
Kwon, N.H.; Kang, T.; Lee, J.Y.; Kim, H.H.; Kim, H.R.; Hong, J.; Oh, Y.S.; Han, J.M.; Ku, M.J.; Lee, S.Y.; Kim, S.
Dual role of methionyl-tRNA synthetase in the regulation of translation and tumor suppressor activity of aminoacyl-tRNA synthetase-interacting multifunctional protein-3
Proc. Natl. Acad. Sci. USA
108
19635-19640
2011
Homo sapiens
brenda
Kim, E.Y.; Jung, J.Y.; Kim, A.; Kim, K.; Chang, Y.S.
Methionyl-tRNA synthetase overexpression is associated with poor clinical outcomes in non-small cell lung cancer
BMC Cancer
17
467
2017
Homo sapiens, Mus musculus
brenda
Bharathkumar, H.; Mohan, C.D.; Rangappa, S.; Kang, T.; Keerthy, H.K.; Fuchs, J.E.; Kwon, N.H.; Bender, A.; Kim, S.; Basappa, S.; Rangappa, K.S.
Screening of quinoline, 1,3-benzoxazine, and 1,3-oxazine-based small molecules against isolated methionyl-tRNA synthetase and A549 and HCT116 cancer cells including an in silico binding mode analysis
Org. Biomol. Chem.
13
9381-9387
2015
Homo sapiens
brenda