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Literature summary extracted from

  • Freiberg, C.; Brunner, N.A.; Schiffer, G.; Lampe, T.; Pohlmann, J.; Brands, M.; Raabe, M.; Habich, D.; Ziegelbauer, K.
    Identification and characterization of the first class of potent bacterial acetyl-CoA carboxylase inhibitors with antibacterial activity (2004), J. Biol. Chem., 279, 26066-26073.
    View publication on PubMed

Activating Compound

EC Number Activating Compound Comment Organism Structure
6.4.1.2 Biocytin biotin derivative, can partly substitute for biotin Staphylococcus aureus
6.4.1.2 Biocytin biotin derivative, can partly substitute for biotin Escherichia coli
6.4.1.2 biotin required for activity Staphylococcus aureus
6.4.1.2 biotin required for activity Escherichia coli

Cloned(Commentary)

EC Number Cloned (Comment) Organism
6.4.1.2 expression of His-tagged enzyme in Escherichia coli strain XL 1-Blue Bacillus subtilis
6.4.1.2 expression of His-tagged enzyme subunits AccA and AccD in Escherichia coli strain XL 1-Blue Staphylococcus aureus
6.4.1.2 expression of His-tagged enzyme subunits AccA and AccD in strain XL 1-Blue Escherichia coli

Protein Variants

EC Number Protein Variants Comment Organism
6.4.1.2 G196S construction and isolation of a mutant strain less sensitive to moiramide B derivative (E)-3-benzo[1,3]dioxol-5-yl-N-[(S)-2-[(S)-2-methyl-1-((3R,4S)-4-methyl-2,5-dioxo-pyrrolidine-3-carbonyl)-propylcarbamoyl]-1-phenyl-ethyl]-acrylamide compared to the wild-type strain Staphylococcus aureus
6.4.1.2 G199S construction and isolation of a mutant strain less sensitive to moiramide B derivative cpd2 compared to the wild-type strain Bacillus subtilis
6.4.1.2 additional information construction and isolation of mutant a strain resistant to moiramide B derivative (E)-3-benzo[1,3]dioxol-5-yl-N-[(S)-2-[(S)-2-methyl-1-((3R,4S)-4-methyl-2,5-dioxo-pyrrolidine-3-carbonyl)-propylcarbamoyl]-1-phenyl-ethyl]-acrylamide Escherichia coli

Inhibitors

EC Number Inhibitors Comment Organism Structure
6.4.1.2 (E)-3-benzo[1,3]dioxol-5-yl-N-[(S)-2-[(S)-2-methyl-1-((3R,4S)-4-methyl-2,5-dioxo-pyrrolidine-3-carbonyl)-propylcarbamoyl]-1-phenyl-ethyl]-acrylamide
-
 Bacillus subtilis
6.4.1.2 (E)-3-benzo[1,3]dioxol-5-yl-N-[(S)-2-[(S)-2-methyl-1-((3R,4S)-4-methyl-2,5-dioxo-pyrrolidine-3-carbonyl)-propylcarbamoyl]-1-phenyl-ethyl]-acrylamide IC50 for the purified recombinant subunits AccA and AccD is 4 nM, for the wild-type enzyme in crude extract 11 nM Escherichia coli
6.4.1.2 (E)-3-benzo[1,3]dioxol-5-yl-N-[(S)-2-[(S)-2-methyl-1-((3R,4S)-4-methyl-2,5-dioxo-pyrrolidine-3-carbonyl)-propylcarbamoyl]-1-phenyl-ethyl]-acrylamide IC50 for the purified recombinant subunits AccA and AccD is 91 nM Staphylococcus aureus
6.4.1.2 (E)-3-biphenyl-4-yl-N-[(S)-2-[(S)-2-methyl-1-((3R,4S)-4-methyl-2,5-dioxo-pyrrolidine-3-carbonyl)-propylcarbamoyl]-1-phenyl-ethyl]-acrylamide
-
 Bacillus subtilis
6.4.1.2 (E)-3-biphenyl-4-yl-N-[(S)-2-[(S)-2-methyl-1-((3R,4S)-4-methyl-2,5-dioxo-pyrrolidine-3-carbonyl)-propylcarbamoyl]-1-phenyl-ethyl]-acrylamide IC50 for the purified recombinant subunits AccA and AccD is 37 nM, for the wild-type enzyme in crude extract 288 nM Escherichia coli
6.4.1.2 (E)-3-biphenyl-4-yl-N-[(S)-2-[(S)-2-methyl-1-((3R,4S)-4-methyl-2,5-dioxo-pyrrolidine-3-carbonyl)-propylcarbamoyl]-1-phenyl-ethyl]-acrylamide IC50 for the purified recombinant subunits AccA and AccD is 540 nM Staphylococcus aureus
6.4.1.2 6-fluoro-pyridine-2-carboxylic acid [(S)-2-[(S)-2-methyl-1-((3R,4S)-4-methyl-2,5-dioxo-pyrrolidine-3-carbonyl)-propylcarbamoyl]-1-phenyl-ethyl]-amide
-
 Bacillus subtilis
6.4.1.2 6-fluoro-pyridine-2-carboxylic acid [(S)-2-[(S)-2-methyl-1-((3R,4S)-4-methyl-2,5-dioxo-pyrrolidine-3-carbonyl)-propylcarbamoyl]-1-phenyl-ethyl]-amide IC50 for the purified recombinant subunits AccA and AccD is 1 nM, for the wild-type enzyme in crude extract 8 nM Escherichia coli
6.4.1.2 6-fluoro-pyridine-2-carboxylic acid [(S)-2-[(S)-2-methyl-1-((3R,4S)-4-methyl-2,5-dioxo-pyrrolidine-3-carbonyl)-propylcarbamoyl]-1-phenyl-ethyl]-amide IC50 for the purified recombinant subunits AccA and AccD is 50 nM Staphylococcus aureus
6.4.1.2 andrimid
-
 Bacillus subtilis
6.4.1.2 andrimid i.e. (2E,4E,6E)-octa-2,4,6-trienoic acid [(S)-2-[(S)-2-methyl-1-((3R,4S)-4-methyl-2,5-dioxo-pyrrolidine-3-carbonyl)-propylcarbamoyl]-1-phenyl-ethyl]-amide, IC50 for the purified recombinant subunits AccA and AccD is 13 nM Escherichia coli
6.4.1.2 andrimid i.e. (2E,4E,6E)-octa-2,4,6-trienoic acid [(S)-2-[(S)-2-methyl-1-((3R,4S)-4-methyl-2,5-dioxo-pyrrolidine-3-carbonyl)-propylcarbamoyl]-1-phenyl-ethyl]-amide, IC50 for the purified recombinant subunits AccA and AccD is 305 nM Staphylococcus aureus
6.4.1.2 moiramide B
-
 Bacillus subtilis
6.4.1.2 moiramide B i.e. (2E,4E)-hexa-2,4-dienoic acid [(S)-2-[(S)-2-methyl-1-((3R,4S)-4-methyl-2,5-dioxo-pyrrolidine-3-carbonyl)-propylcarbamoyl]-1-phenyl-ethyl]-amide, competitive with respect to malonyl-CoA, noncompetitive to biocytin, IC50 for the purified recombinant subunits AccA and AccD is 6 nM, for the wild-type enzyme in crude extract 15 nM Escherichia coli
6.4.1.2 moiramide B i.e. (2E,4E)-hexa-2,4-dienoic acid [(S)-2-[(S)-2-methyl-1-((3R,4S)-4-methyl-2,5-dioxo-pyrrolidine-3-carbonyl)-propylcarbamoyl]-1-phenyl-ethyl]-amide, IC50 for the purified recombinant subunits AccA and AccD is 96 nM Staphylococcus aureus
6.4.1.2 additional information inhibitory and antibacterial potencies of pyrrolidine dione derivatives, overview Bacillus subtilis
6.4.1.2 additional information inhibitory and antibacterial potencies of pyrrolidine dione derivatives, overview Escherichia coli
6.4.1.2 additional information no inhibition of the rat enzyme by pyrrolidine dione moiramide B, i.e. (2E,4E)-hexa-2,4-dienoic acid [(S)-2-[(S)-2-methyl-1-((3R,4S)-4-methyl-2,5-dioxo-pyrrolidine-3-carbonyl)-propylcarbamoyl]-1-phenyl-ethyl]-amide, and its derivatve 6-fluoro-pyridine-2-carboxylic acid [(S)-2-[(S)-2-methyl-1-((3R,4S)-4-methyl-2,5-dioxo-pyrrolidine-3-carbonyl)-propylcarbamoyl]-1-phenyl-ethyl]-amide Rattus norvegicus
6.4.1.2 additional information inhibitory and antibacterial potencies of pyrrolidine dione derivatives, overview Staphylococcus aureus

KM Value [mM]

EC Number KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
6.4.1.2 0.1
-
 malonyl-CoA pH 8.0, recombinant subunits AccA and AccD Escherichia coli
6.4.1.2 0.15
-
 malonyl-CoA pH 8.0, recombinant subunits AccA and AccD Staphylococcus aureus
6.4.1.2 10
-
 Biocytin pH 8.0, recombinant subunits AccA and AccD Escherichia coli
6.4.1.2 70
-
 Biocytin pH 8.0, recombinant subunits AccA and AccD Staphylococcus aureus

Metals/Ions

EC Number Metals/Ions Comment Organism Structure
6.4.1.2 Mg2+
-
 Staphylococcus aureus
6.4.1.2 Mg2+
-
 Bacillus subtilis
6.4.1.2 Mg2+
-
 Escherichia coli
6.4.1.2 Mg2+
-
 Rattus norvegicus

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
6.4.1.2 ATP + acetyl-CoA + HCO3- Rattus norvegicus first step in fatty acid biosynthesis ADP + malonyl-CoA + phosphate
-
 ?
6.4.1.2 ATP + acetyl-CoA + HCO3- Staphylococcus aureus first step in fatty acid biosynthesis via fatty acid synthase type II, overview ADP + malonyl-CoA + phosphate
-
 ?
6.4.1.2 ATP + acetyl-CoA + HCO3- Bacillus subtilis first step in fatty acid biosynthesis via fatty acid synthase type II, overview ADP + malonyl-CoA + phosphate
-
 ?
6.4.1.2 ATP + acetyl-CoA + HCO3- Escherichia coli first step in fatty acid biosynthesis via fatty acid synthase type II, overview ADP + malonyl-CoA + phosphate
-
 ?
6.4.1.2 ATP + acetyl-CoA + HCO3- Escherichia coli MG1655 first step in fatty acid biosynthesis via fatty acid synthase type II, overview ADP + malonyl-CoA + phosphate
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
6.4.1.2 Bacillus subtilis
-
-
-
6.4.1.2 Escherichia coli
-
-
-
6.4.1.2 Escherichia coli MG1655
-
-
-
6.4.1.2 Rattus norvegicus
-
-
-
6.4.1.2 Staphylococcus aureus
-
-
-

Purification (Commentary)

EC Number Purification (Comment) Organism
6.4.1.2 partially from liver by avidin affinity chromatography including a batch step Rattus norvegicus
6.4.1.2 recombinant His-tagged enzyme from Escherichia coli strain XL 1-Blue by nickel affinity chromatography Bacillus subtilis
6.4.1.2 recombinant His-tagged enzyme subunits AccA and AccD from Escherichia coli strain XL 1-Blue by nickel affinity chromatography Staphylococcus aureus
6.4.1.2 recombinant His-tagged enzyme subunits AccA and AccD from strain XL 1-Blue by nickel affinity chromatography Escherichia coli

Source Tissue

EC Number Source Tissue Comment Organism Textmining
6.4.1.2 liver
-
 Rattus norvegicus
-

Specific Activity [micromol/min/mg]

EC Number Specific Activity Minimum [µmol/min/mg] Specific Activity Maximum [µmol/min/mg] Comment Organism
6.4.1.2 0.4
-
 purified recombinant enzyme Staphylococcus aureus

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
6.4.1.2 ATP + acetyl-CoA + HCO3-
-
 Staphylococcus aureus ADP + malonyl-CoA + phosphate
-
 ?
6.4.1.2 ATP + acetyl-CoA + HCO3-
-
 Bacillus subtilis ADP + malonyl-CoA + phosphate
-
 ?
6.4.1.2 ATP + acetyl-CoA + HCO3-
-
 Escherichia coli ADP + malonyl-CoA + phosphate
-
 ?
6.4.1.2 ATP + acetyl-CoA + HCO3-
-
 Rattus norvegicus ADP + malonyl-CoA + phosphate
-
 ?
6.4.1.2 ATP + acetyl-CoA + HCO3- first step in fatty acid biosynthesis Rattus norvegicus ADP + malonyl-CoA + phosphate
-
 ?
6.4.1.2 ATP + acetyl-CoA + HCO3- first step in fatty acid biosynthesis via fatty acid synthase type II, overview Staphylococcus aureus ADP + malonyl-CoA + phosphate
-
 ?
6.4.1.2 ATP + acetyl-CoA + HCO3- first step in fatty acid biosynthesis via fatty acid synthase type II, overview Bacillus subtilis ADP + malonyl-CoA + phosphate
-
 ?
6.4.1.2 ATP + acetyl-CoA + HCO3- first step in fatty acid biosynthesis via fatty acid synthase type II, overview Escherichia coli ADP + malonyl-CoA + phosphate
-
 ?
6.4.1.2 ATP + acetyl-CoA + HCO3-
-
 Escherichia coli MG1655 ADP + malonyl-CoA + phosphate
-
 ?
6.4.1.2 ATP + acetyl-CoA + HCO3- first step in fatty acid biosynthesis via fatty acid synthase type II, overview Escherichia coli MG1655 ADP + malonyl-CoA + phosphate
-
 ?

Synonyms

EC Number Synonyms Comment Organism
6.4.1.2 ACC
-
 Staphylococcus aureus
6.4.1.2 ACC
-
 Bacillus subtilis
6.4.1.2 ACC
-
 Escherichia coli
6.4.1.2 ACC
-
 Rattus norvegicus

pH Optimum

EC Number pH Optimum Minimum pH Optimum Maximum Comment Organism
6.4.1.2 7.4
-
 assay at Rattus norvegicus
6.4.1.2 8
-
 assay at Staphylococcus aureus
6.4.1.2 8
-
 assay at Bacillus subtilis
6.4.1.2 8
-
 assay at Escherichia coli

Cofactor

EC Number Cofactor Comment Organism Structure
6.4.1.2 ATP
-
 Staphylococcus aureus
6.4.1.2 ATP
-
 Bacillus subtilis
6.4.1.2 ATP
-
 Escherichia coli
6.4.1.2 ATP
-
 Rattus norvegicus

Ki Value [mM]

EC Number Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
6.4.1.2 additional information
-
 additional information inhibition kinetics Staphylococcus aureus
6.4.1.2 additional information
-
 additional information inhibition kinetics Escherichia coli

IC50 Value

EC Number IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
6.4.1.2 0.000001
-
 IC50 for the purified recombinant subunits AccA and AccD is 1 nM Escherichia coli 6-fluoro-pyridine-2-carboxylic acid [(S)-2-[(S)-2-methyl-1-((3R,4S)-4-methyl-2,5-dioxo-pyrrolidine-3-carbonyl)-propylcarbamoyl]-1-phenyl-ethyl]-amide
6.4.1.2 0.000004
-
 IC50 for the purified recombinant subunits AccA and AccD is 4 nM Escherichia coli (E)-3-benzo[1,3]dioxol-5-yl-N-[(S)-2-[(S)-2-methyl-1-((3R,4S)-4-methyl-2,5-dioxo-pyrrolidine-3-carbonyl)-propylcarbamoyl]-1-phenyl-ethyl]-acrylamide
6.4.1.2 0.000006
-
 i.e. (2E,4E)-hexa-2,4-dienoic acid [(S)-2-[(S)-2-methyl-1-((3R,4S)-4-methyl-2,5-dioxo-pyrrolidine-3-carbonyl)-propylcarbamoyl]-1-phenyl-ethyl]-amide, competitive with respect to malonyl-CoA, noncompetitive to biocytin, IC50 for the purified recombinant su Escherichia coli moiramide B
6.4.1.2 0.000008
-
 IC 50 for the wild-type enzyme in crude extract 8 nM Escherichia coli 6-fluoro-pyridine-2-carboxylic acid [(S)-2-[(S)-2-methyl-1-((3R,4S)-4-methyl-2,5-dioxo-pyrrolidine-3-carbonyl)-propylcarbamoyl]-1-phenyl-ethyl]-amide
6.4.1.2 0.000011
-
 IC50 for the wild-type enzyme in crude extract 11 nM Escherichia coli (E)-3-benzo[1,3]dioxol-5-yl-N-[(S)-2-[(S)-2-methyl-1-((3R,4S)-4-methyl-2,5-dioxo-pyrrolidine-3-carbonyl)-propylcarbamoyl]-1-phenyl-ethyl]-acrylamide
6.4.1.2 0.000013
-
 i.e. (2E,4E,6E)-octa-2,4,6-trienoic acid [(S)-2-[(S)-2-methyl-1-((3R,4S)-4-methyl-2,5-dioxo-pyrrolidine-3-carbonyl)-propylcarbamoyl]-1-phenyl-ethyl]-amide, IC50 for the purified recombinant subunits AccA and AccD is 13 nM Escherichia coli andrimid
6.4.1.2 0.000037
-
 IC50 for the purified recombinant subunits AccA and AccD is 37 nM Escherichia coli (E)-3-biphenyl-4-yl-N-[(S)-2-[(S)-2-methyl-1-((3R,4S)-4-methyl-2,5-dioxo-pyrrolidine-3-carbonyl)-propylcarbamoyl]-1-phenyl-ethyl]-acrylamide
6.4.1.2 0.00005
-
 IC50 for the purified recombinant subunits AccA and AccD is 50 nM Staphylococcus aureus 6-fluoro-pyridine-2-carboxylic acid [(S)-2-[(S)-2-methyl-1-((3R,4S)-4-methyl-2,5-dioxo-pyrrolidine-3-carbonyl)-propylcarbamoyl]-1-phenyl-ethyl]-amide
6.4.1.2 0.000091
-
 IC50 for the purified recombinant subunits AccA and AccD is 91 nM Staphylococcus aureus (E)-3-benzo[1,3]dioxol-5-yl-N-[(S)-2-[(S)-2-methyl-1-((3R,4S)-4-methyl-2,5-dioxo-pyrrolidine-3-carbonyl)-propylcarbamoyl]-1-phenyl-ethyl]-acrylamide
6.4.1.2 0.000096
-
 i.e. (2E,4E)-hexa-2,4-dienoic acid [(S)-2-[(S)-2-methyl-1-((3R,4S)-4-methyl-2,5-dioxo-pyrrolidine-3-carbonyl)-propylcarbamoyl]-1-phenyl-ethyl]-amide, IC50 for the purified recombinant subunits AccA and AccD is 96 nM Staphylococcus aureus moiramide B
6.4.1.2 0.000288
-
 , for IC50 for the wild-type enzyme in crude extract 288 nM Escherichia coli (E)-3-biphenyl-4-yl-N-[(S)-2-[(S)-2-methyl-1-((3R,4S)-4-methyl-2,5-dioxo-pyrrolidine-3-carbonyl)-propylcarbamoyl]-1-phenyl-ethyl]-acrylamide
6.4.1.2 0.000305
-
 i.e. (2E,4E,6E)-octa-2,4,6-trienoic acid [(S)-2-[(S)-2-methyl-1-((3R,4S)-4-methyl-2,5-dioxo-pyrrolidine-3-carbonyl)-propylcarbamoyl]-1-phenyl-ethyl]-amide, IC50 for the purified recombinant subunits AccA and AccD is 305 nM Staphylococcus aureus andrimid
6.4.1.2 0.00054
-
 IC50 for the purified recombinant subunits AccA and AccD is 540 nM Staphylococcus aureus (E)-3-biphenyl-4-yl-N-[(S)-2-[(S)-2-methyl-1-((3R,4S)-4-methyl-2,5-dioxo-pyrrolidine-3-carbonyl)-propylcarbamoyl]-1-phenyl-ethyl]-acrylamide