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Literature summary extracted from

  • 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 (2009), J. Antimicrob. Chemother., 63, 954-963.
    View publication on PubMed

Application

EC Number Application Comment Organism
6.1.1.10 medicine REP3123 represents a promising narrow spectrum, new mode-of-action agent with an excellent microbiological profile that warrants its further evaluation as a novel drug Staphylococcus aureus
6.1.1.10 medicine REP3123 represents a promising narrow spectrum, new mode-of-action agent with an excellent microbiological profile that warrants its further evaluation as a novel drug Haemophilus influenzae
6.1.1.10 medicine REP3123 represents a promising narrow spectrum, new mode-of-action agent with an excellent microbiological profile that warrants its further evaluation as a novel drug Escherichia coli
6.1.1.10 medicine REP3123 represents a promising narrow spectrum, new mode-of-action agent with an excellent microbiological profile that warrants its further evaluation as a novel drug Homo sapiens
6.1.1.10 medicine REP3123 represents a promising narrow spectrum, new mode-of-action agent with an excellent microbiological profile that warrants its further evaluation as a novel drug Streptococcus pneumoniae
6.1.1.10 medicine REP3123 represents a promising narrow spectrum, new mode-of-action agent with an excellent microbiological profile that warrants its further evaluation as a novel drug to combat Clostridium difficile infections Clostridioides difficile

Cloned(Commentary)

EC Number Cloned (Comment) Organism
6.1.1.10 full-length MetRS with an N-terminal His-tag is overexpressed in Escherichia coli Clostridioides difficile

Protein Variants

EC Number Protein Variants Comment Organism
6.1.1.10 D229E spontaneous resistant mutant, first step Clostridioides difficile
6.1.1.10 D229N serial passage mutant Clostridioides difficile
6.1.1.10 D229N spontaneous resistant mutant, first step Clostridioides difficile
6.1.1.10 G213C spontaneous resistant mutant, first step Clostridioides difficile
6.1.1.10 G213D spontaneous resistant mutant, first step Clostridioides difficile
6.1.1.10 G54A spontaneous resistant mutant, first step Clostridioides difficile
6.1.1.10 G54C spontaneous resistant mutant, first step Clostridioides difficile
6.1.1.10 G54S spontaneous resistant mutant, first step Clostridioides difficile
6.1.1.10 G54S/L203S spontaneous resistant mutant, second step Clostridioides difficile
6.1.1.10 H101D spontaneous resistant mutant, first step Clostridioides difficile
6.1.1.10 H101L spontaneous resistant mutant, first step Clostridioides difficile
6.1.1.10 H101N spontaneous resistant mutant, first step Clostridioides difficile
6.1.1.10 H101N/G213C spontaneous resistant mutant, second step Clostridioides difficile
6.1.1.10 I105M/G213D spontaneous resistant mutant, second step Clostridioides difficile
6.1.1.10 I57N spontaneous resistant mutant, first step Clostridioides difficile
6.1.1.10 I57N/H101N spontaneous resistant mutant, second step Clostridioides difficile
6.1.1.10 T236K spontaneous resistant mutant, first step Clostridioides difficile
6.1.1.10 V216A spontaneous resistant mutant, first step Clostridioides difficile
6.1.1.10 V216F/L203S spontaneous resistant mutant, second step Clostridioides difficile

Inhibitors

EC Number Inhibitors Comment Organism Structure
6.1.1.10 REP3123 active against a collection of 108 clinical isolates of Clostridium difficile and against epidemic, moxifloxacin-resistant BI/NAP1/027 strains Clostridioides difficile
6.1.1.10 REP3123
-
 Escherichia coli
6.1.1.10 REP3123
-
 Haemophilus influenzae
6.1.1.10 REP3123
-
 Homo sapiens
6.1.1.10 REP3123
-
 Staphylococcus aureus
6.1.1.10 REP3123
-
 Streptococcus pneumoniae

KM Value [mM]

EC Number KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
6.1.1.10 0.00055
-
 tRNAMet wild-type, second step of reaction, tRNA aminoacylation Clostridioides difficile
6.1.1.10 0.00064
-
 tRNAMet mutant G54S/L203S, second step of reaction, tRNA aminoacylation Clostridioides difficile
6.1.1.10 0.00065
-
 tRNAMet mutant D229E, second step of reaction, tRNA aminoacylation Clostridioides difficile
6.1.1.10 0.0008
-
 tRNAMet mutant V216A, second step of reaction, tRNA aminoacylation Clostridioides difficile
6.1.1.10 0.00096
-
 tRNAMet mutant V216F/L203S, second step of reaction, tRNA aminoacylation Clostridioides difficile
6.1.1.10 0.00102
-
 tRNAMet mutant G54S, second step of reaction, tRNA aminoacylation Clostridioides difficile
6.1.1.10 0.00121
-
 tRNAMet mutant I57N/H101N, second step of reaction, tRNA aminoacylation Clostridioides difficile
6.1.1.10 0.0026
-
 tRNAMet mutant I57N, second step of reaction, tRNA aminoacylation Clostridioides difficile
6.1.1.10 0.006
-
 L-methionine mutant I57N, first step of reaction, methionyl-adenylate formation Clostridioides difficile
6.1.1.10 0.017
-
 L-methionine mutant V216A, first step of reaction, methionyl-adenylate formation Clostridioides difficile
6.1.1.10 0.025
-
 L-methionine mutant V216F/L203S, first step of reaction, methionyl-adenylate formation Clostridioides difficile
6.1.1.10 0.025
-
 L-methionine wild-type, first step of reaction, methionyl-adenylate formation Clostridioides difficile
6.1.1.10 0.055
-
 L-methionine mutant G54S/L203S, first step of reaction, methionyl-adenylate formation Clostridioides difficile
6.1.1.10 0.092
-
 L-methionine mutant D229E, first step of reaction, methionyl-adenylate formation Clostridioides difficile
6.1.1.10 0.16
-
 L-methionine mutant G54S, first step of reaction, methionyl-adenylate formation Clostridioides difficile
6.1.1.10 0.19
-
 L-methionine mutant I57N/H101N, first step of reaction, methionyl-adenylate formation Clostridioides difficile
6.1.1.10 0.375
-
 ATP wild-type, first step of reaction, methionyl-adenylate formation Clostridioides difficile
6.1.1.10 0.44
-
 ATP mutant G54S, first step of reaction, methionyl-adenylate formation Clostridioides difficile
6.1.1.10 0.475
-
 ATP mutant H101N/G213C, first step of reaction, methionyl-adenylate formation Clostridioides difficile
6.1.1.10 0.7
-
 ATP mutant H101D, first step of reaction, methionyl-adenylate formation Clostridioides difficile
6.1.1.10 0.78
-
 ATP mutant V216A, first step of reaction, methionyl-adenylate formation Clostridioides difficile
6.1.1.10 0.85
-
 ATP mutant V216F/L203S, first step of reaction, methionyl-adenylate formation Clostridioides difficile
6.1.1.10 0.98
-
 ATP mutant D229E, first step of reaction, methionyl-adenylate formation Clostridioides difficile
6.1.1.10 1
-
 ATP mutant I57N, first step of reaction, methionyl-adenylate formation Clostridioides difficile
6.1.1.10 1.35
-
 ATP mutant G54S/L203S, first step of reaction, methionyl-adenylate formation Clostridioides difficile
6.1.1.10 1.55
-
 L-methionine mutant H101N/G213C, first step of reaction, methionyl-adenylate formation Clostridioides difficile
6.1.1.10 1.75
-
 ATP mutant I57N/H101N, first step of reaction, methionyl-adenylate formation Clostridioides difficile
6.1.1.10 14.8
-
 L-methionine mutant H101D, first step of reaction, methionyl-adenylate formation Clostridioides difficile

Localization

EC Number Localization Comment Organism GeneOntology No. Textmining
6.1.1.10 cytoplasm
-
 Homo sapiens 5737
-
6.1.1.10 mitochondrion
-
 Homo sapiens 5739
-

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
6.1.1.10 ATP + L-methionine + tRNAMet Staphylococcus aureus
-
 AMP + diphosphate + L-methionyl-tRNAMet
-
 ?
6.1.1.10 ATP + L-methionine + tRNAMet Haemophilus influenzae
-
 AMP + diphosphate + L-methionyl-tRNAMet
-
 ?
6.1.1.10 ATP + L-methionine + tRNAMet Escherichia coli
-
 AMP + diphosphate + L-methionyl-tRNAMet
-
 ?
6.1.1.10 ATP + L-methionine + tRNAMet Homo sapiens
-
 AMP + diphosphate + L-methionyl-tRNAMet
-
 ?
6.1.1.10 ATP + L-methionine + tRNAMet Streptococcus pneumoniae
-
 AMP + diphosphate + L-methionyl-tRNAMet
-
 ?
6.1.1.10 ATP + L-methionine + tRNAMet Clostridioides difficile
-
 AMP + diphosphate + L-methionyl-tRNAMet
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
6.1.1.10 Clostridioides difficile
-
-
-
6.1.1.10 Escherichia coli
-
-
-
6.1.1.10 Haemophilus influenzae
-
-
-
6.1.1.10 Homo sapiens
-
-
-
6.1.1.10 Staphylococcus aureus
-
-
-
6.1.1.10 Streptococcus pneumoniae
-
-
-

Purification (Commentary)

EC Number Purification (Comment) Organism
6.1.1.10 using Ni-affinity and SourceQ anion exchange chromatography Clostridioides difficile

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
6.1.1.10 ATP + L-methionine + tRNAMet
-
 Staphylococcus aureus AMP + diphosphate + L-methionyl-tRNAMet
-
 ?
6.1.1.10 ATP + L-methionine + tRNAMet
-
 Haemophilus influenzae AMP + diphosphate + L-methionyl-tRNAMet
-
 ?
6.1.1.10 ATP + L-methionine + tRNAMet
-
 Escherichia coli AMP + diphosphate + L-methionyl-tRNAMet
-
 ?
6.1.1.10 ATP + L-methionine + tRNAMet
-
 Homo sapiens AMP + diphosphate + L-methionyl-tRNAMet
-
 ?
6.1.1.10 ATP + L-methionine + tRNAMet
-
 Streptococcus pneumoniae AMP + diphosphate + L-methionyl-tRNAMet
-
 ?
6.1.1.10 ATP + L-methionine + tRNAMet
-
 Clostridioides difficile AMP + diphosphate + L-methionyl-tRNAMet
-
 ?

Synonyms

EC Number Synonyms Comment Organism
6.1.1.10 methionyl-tRNA synthetase
-
 Staphylococcus aureus
6.1.1.10 methionyl-tRNA synthetase
-
 Haemophilus influenzae
6.1.1.10 methionyl-tRNA synthetase
-
 Escherichia coli
6.1.1.10 methionyl-tRNA synthetase
-
 Homo sapiens
6.1.1.10 methionyl-tRNA synthetase
-
 Streptococcus pneumoniae
6.1.1.10 methionyl-tRNA synthetase
-
 Clostridioides difficile
6.1.1.10 MetRS
-
 Staphylococcus aureus
6.1.1.10 MetRS
-
 Haemophilus influenzae
6.1.1.10 MetRS
-
 Escherichia coli
6.1.1.10 MetRS
-
 Homo sapiens
6.1.1.10 MetRS
-
 Streptococcus pneumoniae
6.1.1.10 MetRS
-
 Clostridioides difficile
6.1.1.10 MetRS1
-
 Streptococcus pneumoniae
6.1.1.10 MetRS2
-
 Streptococcus pneumoniae

Turnover Number [1/s]

EC Number Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
6.1.1.10 0.006
-
 tRNAMet mutant V216F/L203S, second step of reaction, tRNA aminoacylation Clostridioides difficile
6.1.1.10 0.01
-
 tRNAMet mutant G54S, second step of reaction, tRNA aminoacylation Clostridioides difficile
6.1.1.10 0.011
-
 tRNAMet mutant G54S/L203S, second step of reaction, tRNA aminoacylation Clostridioides difficile
6.1.1.10 0.013
-
 tRNAMet mutant I57N/H101N, second step of reaction, tRNA aminoacylation Clostridioides difficile
6.1.1.10 0.017
-
 tRNAMet mutant I57N, second step of reaction, tRNA aminoacylation Clostridioides difficile
6.1.1.10 0.023
-
 tRNAMet mutant D229E, second step of reaction, tRNA aminoacylation Clostridioides difficile
6.1.1.10 0.055
-
 tRNAMet mutant V216A, second step of reaction, tRNA aminoacylation Clostridioides difficile
6.1.1.10 0.08
-
 tRNAMet wild-type, second step of reaction, tRNA aminoacylation Clostridioides difficile
6.1.1.10 4
-
 L-methionine mutant G54S, first step of reaction, methionyl-adenylate formation Clostridioides difficile
6.1.1.10 6
-
 L-methionine mutant I57N/H101N, first step of reaction, methionyl-adenylate formation Clostridioides difficile
6.1.1.10 8
-
 L-methionine mutant H101N/G213C, first step of reaction, methionyl-adenylate formation Clostridioides difficile
6.1.1.10 15
-
 L-methionine mutant G54S/L203S, first step of reaction, methionyl-adenylate formation Clostridioides difficile
6.1.1.10 15
-
 L-methionine mutant H101D, first step of reaction, methionyl-adenylate formation Clostridioides difficile
6.1.1.10 15
-
 L-methionine mutant I57N, first step of reaction, methionyl-adenylate formation Clostridioides difficile
6.1.1.10 23
-
 L-methionine wild-type, first step of reaction, methionyl-adenylate formation Clostridioides difficile
6.1.1.10 25
-
 L-methionine mutant V216A, first step of reaction, methionyl-adenylate formation Clostridioides difficile
6.1.1.10 25
-
 L-methionine mutant V216F/L203S, first step of reaction, methionyl-adenylate formation Clostridioides difficile
6.1.1.10 33
-
 L-methionine mutant D229E, first step of reaction, methionyl-adenylate formation Clostridioides difficile

Cofactor

EC Number Cofactor Comment Organism Structure
6.1.1.10 ATP
-
 Staphylococcus aureus
6.1.1.10 ATP
-
 Haemophilus influenzae
6.1.1.10 ATP
-
 Escherichia coli
6.1.1.10 ATP
-
 Homo sapiens
6.1.1.10 ATP
-
 Streptococcus pneumoniae
6.1.1.10 ATP
-
 Clostridioides difficile

Ki Value [mM]

EC Number Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
6.1.1.10 0.000000017
-
 REP3123
-
 Staphylococcus aureus
6.1.1.10 0.00000002
-
 REP3123 wild-type Clostridioides difficile
6.1.1.10 0.00000008
-
 REP3123 MetRS1 Streptococcus pneumoniae
6.1.1.10 0.0000002
-
 REP3123 mutant I57N Clostridioides difficile
6.1.1.10 0.00001
-
 REP3123 mutant V216F/L203S Clostridioides difficile
6.1.1.10 0.000013
-
 REP3123 mutant G54S Clostridioides difficile
6.1.1.10 0.000018
-
 REP3123 mutant D229E Clostridioides difficile
6.1.1.10 0.000028
-
 REP3123 mitochondrial MetRS Homo sapiens
6.1.1.10 0.00007
-
 REP3123 mutant V216A Clostridioides difficile
6.1.1.10 0.000155
-
 REP3123 mutant I57N/H101N Clostridioides difficile
6.1.1.10 0.000178
-
 REP3123
-
 Haemophilus influenzae
6.1.1.10 0.000375
-
 REP3123 mutant H101D Clostridioides difficile
6.1.1.10 0.0005
-
 REP3123 mutant G54S/L203S Clostridioides difficile
6.1.1.10 0.001
-
 REP3123 mutant H101N/G213C Clostridioides difficile
6.1.1.10 0.0019
-
 REP3123
-
 Escherichia coli
6.1.1.10 0.02
-
 REP3123 cytoplasmic MetRS Homo sapiens
6.1.1.10 0.02
-
 REP3123 MetRS2 Streptococcus pneumoniae