Application | Comment | Organism |
---|---|---|
medicine | REP8839 is a selective inhibitor of methionyl-tRNA synthetase with antibacterial activity against a variety of gram-positive organisms | Staphylococcus aureus |
medicine | REP8839 is a selective inhibitor of methionyl-tRNA synthetase with antibacterial activity against a variety of gram-positive organisms | Haemophilus influenzae |
medicine | REP8839 is a selective inhibitor of methionyl-tRNA synthetase with antibacterial activity against a variety of gram-positive organisms | Escherichia coli |
medicine | REP8839 is a selective inhibitor of methionyl-tRNA synthetase with antibacterial activity against a variety of gram-positive organisms | Homo sapiens |
medicine | REP8839 is a selective inhibitor of methionyl-tRNA synthetase with antibacterial activity against a variety of gram-positive organisms | Streptococcus pneumoniae |
Cloned (Comment) | Organism |
---|---|
bacterial strains, DH5alpha, containing pPROLar plasmids carrying the gene encoding MetRS1 are used | Streptococcus pneumoniae |
into an inducible Escherichia expression vector | Staphylococcus aureus |
plasmid pcDNA3.1MRS, containing a gene encoding hcMetRS, and plasmid pcDNA3.1MRSce2, containing a gene encoding full-length hmMetRS, are used, genes are inserted into pET100/D-TOPO vectors | Homo sapiens |
Protein Variants | Comment | Organism |
---|---|---|
A247E | mutant MetRS | Staphylococcus aureus |
G223C | mutant MetRS | Staphylococcus aureus |
G54A/A64P | mutant MetRS | Staphylococcus aureus |
G54S | mutant MetRS | Staphylococcus aureus |
I57N | mutant MetRS | Staphylococcus aureus |
I57N/A247E | mutant MetRS | Staphylococcus aureus |
I57N/G54S | mutant MetRS | Staphylococcus aureus |
I57N/I238F | mutant MetRS | Staphylococcus aureus |
I57N/V242F | mutant MetRS | Staphylococcus aureus |
L213W | mutant MetRS | Staphylococcus aureus |
V108M | mutant MetRS | Staphylococcus aureus |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
REP8839 | - |
Escherichia coli | |
REP8839 | - |
Haemophilus influenzae | |
REP8839 | - |
Homo sapiens | |
REP8839 | - |
Staphylococcus aureus | |
REP8839 | - |
Streptococcus pneumoniae |
KM Value [mM] | KM Value Maximum [mM] | Substrate | Comment | Organism | Structure |
---|---|---|---|---|---|
0.00027 | - |
tRNAMet | mutant G54S, aminoacylation reaction | Staphylococcus aureus | |
0.00041 | - |
tRNAMet | mutant I57N/G54S, aminoacylation reaction | Staphylococcus aureus | |
0.00045 | - |
tRNAMet | mutant I57N/A247E, aminoacylation reaction | Staphylococcus aureus | |
0.00057 | - |
tRNAMet | mutant G54A/A64P, aminoacylation reaction | Staphylococcus aureus | |
0.00089 | - |
tRNAMet | mutant I57N/I238F, aminoacylation reaction | Staphylococcus aureus | |
0.00093 | - |
tRNAMet | mutant I57N, aminoacylation reaction | Staphylococcus aureus | |
0.001 | - |
tRNAMet | wild-type, aminoacylation reaction | Staphylococcus aureus | |
0.0013 | - |
tRNAMet | mutant A247E, aminoacylation reaction | Staphylococcus aureus | |
0.0017 | - |
tRNAMet | mutant L213W, aminoacylation reaction | Staphylococcus aureus | |
0.0025 | - |
tRNAMet | mutant G223C, aminoacylation reaction | Staphylococcus aureus | |
0.0032 | - |
tRNAMet | mutant V108M, aminoacylation reaction | Staphylococcus aureus | |
0.01 | - |
tRNAMet | mutant I57N/V242F, aminoacylation reaction | Staphylococcus aureus | |
0.02 | - |
L-methionine | - |
Homo sapiens | |
0.02 | - |
L-methionine | mutant I57N/V242F, ATP:diphosphate exchange reaction | Staphylococcus aureus | |
0.025 | - |
L-methionine | mutant I57N, ATP:diphosphate exchange reaction | Staphylococcus aureus | |
0.053 | - |
L-methionine | - |
Streptococcus pneumoniae | |
0.075 | - |
L-methionine | mutant G54S, ATP:diphosphate exchange reaction | Staphylococcus aureus | |
0.085 | - |
ATP | - |
Homo sapiens | |
0.085 | - |
L-methionine | mutant I57N/I238F, ATP:diphosphate exchange reaction | Staphylococcus aureus | |
0.1 | - |
L-methionine | mutant L213W, ATP:diphosphate exchange reaction | Staphylococcus aureus | |
0.1 | - |
L-methionine | wild-type, ATP:diphosphate exchange reaction | Staphylococcus aureus | |
0.14 | - |
L-methionine | mutant V108M, ATP:diphosphate exchange reaction | Staphylococcus aureus | |
0.22 | - |
L-methionine | mutant A247E, ATP:diphosphate exchange reaction | Staphylococcus aureus | |
0.25 | - |
L-methionine | - |
Haemophilus influenzae | |
0.25 | - |
L-methionine | mutant I57N/A247E, ATP:diphosphate exchange reaction | Staphylococcus aureus | |
0.36 | - |
L-methionine | mutant I57N/G54S, ATP:diphosphate exchange reaction | Staphylococcus aureus | |
0.5 | - |
ATP | mutant G54S, ATP:diphosphate exchange reaction | Staphylococcus aureus | |
0.5 | - |
ATP | wild-type, ATP:diphosphate exchange reaction | Staphylococcus aureus | |
0.514 | - |
ATP | - |
Streptococcus pneumoniae | |
0.595 | - |
ATP | mutant L213W, ATP:diphosphate exchange reaction | Staphylococcus aureus | |
0.65 | - |
ATP | mutant V108M, ATP:diphosphate exchange reaction | Staphylococcus aureus | |
0.68 | - |
L-methionine | mutant G223C, ATP:diphosphate exchange reaction | Staphylococcus aureus | |
0.75 | - |
ATP | mutant G223C, ATP:diphosphate exchange reaction | Staphylococcus aureus | |
0.76 | - |
ATP | mutant G54A/A64P, ATP:diphosphate exchange reaction | Staphylococcus aureus | |
0.765 | - |
ATP | mutant I57N/G54S, ATP:diphosphate exchange reaction | Staphylococcus aureus | |
0.81 | - |
ATP | mutant I57N/V242F, ATP:diphosphate exchange reaction | Staphylococcus aureus | |
0.82 | - |
ATP | mutant I57N, ATP:diphosphate exchange reaction | Staphylococcus aureus | |
1.07 | - |
L-methionine | mutant G54A/A64P, ATP:diphosphate exchange reaction | Staphylococcus aureus | |
1.14 | - |
ATP | mutant A247E, ATP:diphosphate exchange reaction | Staphylococcus aureus | |
1.2 | - |
ATP | - |
Haemophilus influenzae | |
1.61 | - |
ATP | mutant I57N/I238F, ATP:diphosphate exchange reaction | Staphylococcus aureus | |
2.23 | - |
ATP | mutant I57N/A247E, ATP:diphosphate exchange reaction | Staphylococcus aureus |
Localization | Comment | Organism | GeneOntology No. | Textmining |
---|---|---|---|---|
cytoplasm | hcMetRS | Homo sapiens | 5737 | - |
mitochondrion | hmMetRS | Homo sapiens | 5739 | - |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
ATP + L-methionine + tRNAMet | Staphylococcus aureus | - |
AMP + diphosphate + L-methionyl-tRNAMet | - |
? | |
ATP + L-methionine + tRNAMet | Haemophilus influenzae | - |
AMP + diphosphate + L-methionyl-tRNAMet | - |
? | |
ATP + L-methionine + tRNAMet | Escherichia coli | - |
AMP + diphosphate + L-methionyl-tRNAMet | - |
? | |
ATP + L-methionine + tRNAMet | Homo sapiens | - |
AMP + diphosphate + L-methionyl-tRNAMet | - |
? | |
ATP + L-methionine + tRNAMet | Streptococcus pneumoniae | - |
AMP + diphosphate + L-methionyl-tRNAMet | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Escherichia coli | - |
- |
- |
Haemophilus influenzae | - |
- |
- |
Homo sapiens | - |
- |
- |
Staphylococcus aureus | - |
- |
- |
Streptococcus pneumoniae | - |
- |
- |
Purification (Comment) | Organism |
---|---|
by ammonium sulfate precipitation and anion-exchange chromatography on a Source 15Q column | Staphylococcus aureus |
by ammonium sulfate precipitation and anion-exchange chromatography on a Source 15Q column | Streptococcus pneumoniae |
using Ni-nitrilotriacetic acid resin | Homo sapiens |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
ATP + L-methionine + tRNAMet | - |
Staphylococcus aureus | AMP + diphosphate + L-methionyl-tRNAMet | - |
? | |
ATP + L-methionine + tRNAMet | - |
Haemophilus influenzae | AMP + diphosphate + L-methionyl-tRNAMet | - |
? | |
ATP + L-methionine + tRNAMet | - |
Escherichia coli | AMP + diphosphate + L-methionyl-tRNAMet | - |
? | |
ATP + L-methionine + tRNAMet | - |
Homo sapiens | AMP + diphosphate + L-methionyl-tRNAMet | - |
? | |
ATP + L-methionine + tRNAMet | - |
Streptococcus pneumoniae | AMP + diphosphate + L-methionyl-tRNAMet | - |
? |
Synonyms | Comment | Organism |
---|---|---|
hcMetRS | - |
Homo sapiens |
hmMetRS | - |
Homo sapiens |
methionyl-tRNA synthetase | - |
Staphylococcus aureus |
methionyl-tRNA synthetase | - |
Haemophilus influenzae |
methionyl-tRNA synthetase | - |
Escherichia coli |
methionyl-tRNA synthetase | - |
Homo sapiens |
methionyl-tRNA synthetase1 | - |
Streptococcus pneumoniae |
MetRS | - |
Staphylococcus aureus |
MetRS | - |
Haemophilus influenzae |
MetRS | - |
Escherichia coli |
MetRS | - |
Homo sapiens |
MetRS1 | - |
Streptococcus pneumoniae |
Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
---|---|---|---|
22 | - |
tRNA aminoacylation assay at room temperature for 30 min for IC50 determinations | Staphylococcus aureus |
22 | - |
tRNA aminoacylation assay at room temperature for 30 min for IC50 determinations | Haemophilus influenzae |
22 | - |
tRNA aminoacylation assay at room temperature for 30 min for IC50 determinations | Escherichia coli |
22 | - |
tRNA aminoacylation assay at room temperature for 30 min for IC50 determinations | Homo sapiens |
22 | - |
tRNA aminoacylation assay at room temperature for 30 min for IC50 determinations | Streptococcus pneumoniae |
30 | - |
tRNA aminoacylation assay at 30°C for 1 to 7.5 min for initial rate determination | Staphylococcus aureus |
30 | - |
tRNA aminoacylation assay at 30°C for 1 to 7.5 min for initial rate determination | Haemophilus influenzae |
30 | - |
tRNA aminoacylation assay at 30°C for 1 to 7.5 min for initial rate determination | Escherichia coli |
30 | - |
tRNA aminoacylation assay at 30°C for 1 to 7.5 min for initial rate determination | Homo sapiens |
30 | - |
tRNA aminoacylation assay at 30°C for 1 to 7.5 min for initial rate determination | Streptococcus pneumoniae |
Turnover Number Minimum [1/s] | Turnover Number Maximum [1/s] | Substrate | Comment | Organism | Structure |
---|---|---|---|---|---|
0.001 | - |
tRNAMet | mutant G54A/A64P, aminoacylation reaction | Staphylococcus aureus | |
0.002 | - |
tRNAMet | mutant I57N/G54S, aminoacylation reaction | Staphylococcus aureus | |
0.008 | - |
tRNAMet | mutant I57N/A247E, aminoacylation reaction | Staphylococcus aureus | |
0.009 | - |
tRNAMet | mutant G54S, aminoacylation reaction | Staphylococcus aureus | |
0.023 | - |
tRNAMet | mutant I57N, aminoacylation reaction | Staphylococcus aureus | |
0.037 | - |
tRNAMet | mutant G223C, aminoacylation reaction | Staphylococcus aureus | |
0.057 | - |
tRNAMet | mutant A247E, aminoacylation reaction | Staphylococcus aureus | |
0.066 | - |
tRNAMet | mutant I57N/I238F, aminoacylation reaction | Staphylococcus aureus | |
0.124 | - |
tRNAMet | mutant I57N/V242F, aminoacylation reaction | Staphylococcus aureus | |
0.49 | - |
tRNAMet | wild-type, aminoacylation reaction | Staphylococcus aureus | |
0.54 | - |
tRNAMet | mutant L213W, aminoacylation reaction | Staphylococcus aureus | |
0.74 | - |
tRNAMet | mutant V108M, aminoacylation reaction | Staphylococcus aureus | |
1 | - |
L-methionine | mutant G54A/A64P, ATP:diphosphate exchange reaction | Staphylococcus aureus | |
5 | - |
L-methionine | mutant G54S, ATP:diphosphate exchange reaction | Staphylococcus aureus | |
6 | - |
L-methionine | mutant I57N/G54S, ATP:diphosphate exchange reaction | Staphylococcus aureus | |
10 | - |
L-methionine | mutant G223C, ATP:diphosphate exchange reaction | Staphylococcus aureus | |
10 | - |
L-methionine | mutant L213W, ATP:diphosphate exchange reaction | Staphylococcus aureus | |
11 | - |
L-methionine | mutant A247E, ATP:diphosphate exchange reaction | Staphylococcus aureus | |
11 | - |
L-methionine | mutant I57N/A247E, ATP:diphosphate exchange reaction | Staphylococcus aureus | |
13 | - |
L-methionine | mutant I57N/I238F, ATP:diphosphate exchange reaction | Staphylococcus aureus | |
14 | - |
L-methionine | mutant I57N, ATP:diphosphate exchange reaction | Staphylococcus aureus | |
14 | - |
L-methionine | mutant I57N/V242F, ATP:diphosphate exchange reaction | Staphylococcus aureus | |
15 | - |
L-methionine | mutant V108M, ATP:diphosphate exchange reaction | Staphylococcus aureus | |
25 | - |
L-methionine | wild-type, ATP:diphosphate exchange reaction | Staphylococcus aureus |
pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
---|---|---|---|
7.8 | - |
tRNA aminoacylation assay | Homo sapiens |
8 | - |
tRNA aminoacylation assay | Staphylococcus aureus |
8 | - |
tRNA aminoacylation assay | Haemophilus influenzae |
8 | - |
tRNA aminoacylation assay | Escherichia coli |
8 | - |
tRNA aminoacylation assay | Streptococcus pneumoniae |
Cofactor | Comment | Organism | Structure |
---|---|---|---|
ATP | - |
Staphylococcus aureus | |
ATP | - |
Haemophilus influenzae | |
ATP | - |
Escherichia coli | |
ATP | - |
Homo sapiens | |
ATP | - |
Streptococcus pneumoniae |
Ki Value [mM] | Ki Value maximum [mM] | Inhibitor | Comment | Organism | Structure |
---|---|---|---|---|---|
0.00000001 | - |
REP8839 | wild-type | Staphylococcus aureus | |
0.00000004 | - |
REP8839 | mutant L213W | Staphylococcus aureus | |
0.000000055 | - |
REP8839 | - |
Streptococcus pneumoniae | |
0.00000006 | - |
REP8839 | mutant A247E | Staphylococcus aureus | |
0.00000008 | - |
REP8839 | mutant I57N | Staphylococcus aureus | |
0.00000011 | - |
REP8839 | mutant V108M | Staphylococcus aureus | |
0.00000051 | - |
REP8839 | mutant G223C | Staphylococcus aureus | |
0.00001 | - |
REP8839 | hmMetRS | Homo sapiens | |
0.000015 | - |
REP8839 | mutant I57N/V242F | Staphylococcus aureus | |
0.000023 | - |
REP8839 | - |
Haemophilus influenzae | |
0.00006 | - |
REP8839 | mutant I57N/A247E | Staphylococcus aureus | |
0.000085 | - |
REP8839 | mutant G54S | Staphylococcus aureus | |
0.000225 | - |
REP8839 | - |
Escherichia coli | |
0.00035 | - |
REP8839 | mutant I57N/I238F | Staphylococcus aureus | |
0.0009 | - |
REP8839 | mutant I57N/G54S | Staphylococcus aureus | |
0.0019 | - |
REP8839 | mutant G54A/A64P | Staphylococcus aureus | |
0.02 | - |
REP8839 | hcMetRS, larger than 0.020 | Homo sapiens |