Activating Compound | Comment | Organism | Structure |
---|---|---|---|
Biocytin | biotin derivative, can partly substitute for biotin | Staphylococcus aureus | |
Biocytin | biotin derivative, can partly substitute for biotin | Escherichia coli | |
biotin | required for activity | Staphylococcus aureus | |
biotin | required for activity | Escherichia coli |
Cloned (Comment) | Organism |
---|---|
expression of His-tagged enzyme in Escherichia coli strain XL 1-Blue | Bacillus subtilis |
expression of His-tagged enzyme subunits AccA and AccD in Escherichia coli strain XL 1-Blue | Staphylococcus aureus |
expression of His-tagged enzyme subunits AccA and AccD in strain XL 1-Blue | Escherichia coli |
Protein Variants | Comment | Organism |
---|---|---|
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 |
G199S | construction and isolation of a mutant strain less sensitive to moiramide B derivative cpd2 compared to the wild-type strain | Bacillus subtilis |
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 | Comment | Organism | Structure |
---|---|---|---|
(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 | |
(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 | |
(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 | |
(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 | |
(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 | |
(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-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-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-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 | |
andrimid | - |
Bacillus subtilis | |
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 | |
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 | |
moiramide B | - |
Bacillus subtilis | |
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 | |
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 | |
additional information | inhibitory and antibacterial potencies of pyrrolidine dione derivatives, overview | Bacillus subtilis | |
additional information | inhibitory and antibacterial potencies of pyrrolidine dione derivatives, overview | Escherichia coli | |
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 | |
additional information | inhibitory and antibacterial potencies of pyrrolidine dione derivatives, overview | Staphylococcus aureus |
KM Value [mM] | KM Value Maximum [mM] | Substrate | Comment | Organism | Structure |
---|---|---|---|---|---|
0.1 | - |
malonyl-CoA | pH 8.0, recombinant subunits AccA and AccD | Escherichia coli | |
0.15 | - |
malonyl-CoA | pH 8.0, recombinant subunits AccA and AccD | Staphylococcus aureus | |
10 | - |
Biocytin | pH 8.0, recombinant subunits AccA and AccD | Escherichia coli | |
70 | - |
Biocytin | pH 8.0, recombinant subunits AccA and AccD | Staphylococcus aureus |
Metals/Ions | Comment | Organism | Structure |
---|---|---|---|
Mg2+ | - |
Staphylococcus aureus | |
Mg2+ | - |
Bacillus subtilis | |
Mg2+ | - |
Escherichia coli | |
Mg2+ | - |
Rattus norvegicus |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
ATP + acetyl-CoA + HCO3- | Rattus norvegicus | first step in fatty acid biosynthesis | ADP + malonyl-CoA + phosphate | - |
? | |
ATP + acetyl-CoA + HCO3- | Staphylococcus aureus | first step in fatty acid biosynthesis via fatty acid synthase type II, overview | ADP + malonyl-CoA + phosphate | - |
? | |
ATP + acetyl-CoA + HCO3- | Bacillus subtilis | first step in fatty acid biosynthesis via fatty acid synthase type II, overview | ADP + malonyl-CoA + phosphate | - |
? | |
ATP + acetyl-CoA + HCO3- | Escherichia coli | first step in fatty acid biosynthesis via fatty acid synthase type II, overview | ADP + malonyl-CoA + phosphate | - |
? | |
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 | UniProt | Comment | Textmining |
---|---|---|---|
Bacillus subtilis | - |
- |
- |
Escherichia coli | - |
- |
- |
Escherichia coli MG1655 | - |
- |
- |
Rattus norvegicus | - |
- |
- |
Staphylococcus aureus | - |
- |
- |
Purification (Comment) | Organism |
---|---|
partially from liver by avidin affinity chromatography including a batch step | Rattus norvegicus |
recombinant His-tagged enzyme from Escherichia coli strain XL 1-Blue by nickel affinity chromatography | Bacillus subtilis |
recombinant His-tagged enzyme subunits AccA and AccD from Escherichia coli strain XL 1-Blue by nickel affinity chromatography | Staphylococcus aureus |
recombinant His-tagged enzyme subunits AccA and AccD from strain XL 1-Blue by nickel affinity chromatography | Escherichia coli |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
liver | - |
Rattus norvegicus | - |
Specific Activity Minimum [µmol/min/mg] | Specific Activity Maximum [µmol/min/mg] | Comment | Organism |
---|---|---|---|
0.4 | - |
purified recombinant enzyme | Staphylococcus aureus |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
ATP + acetyl-CoA + HCO3- | - |
Staphylococcus aureus | ADP + malonyl-CoA + phosphate | - |
? | |
ATP + acetyl-CoA + HCO3- | - |
Bacillus subtilis | ADP + malonyl-CoA + phosphate | - |
? | |
ATP + acetyl-CoA + HCO3- | - |
Escherichia coli | ADP + malonyl-CoA + phosphate | - |
? | |
ATP + acetyl-CoA + HCO3- | - |
Rattus norvegicus | ADP + malonyl-CoA + phosphate | - |
? | |
ATP + acetyl-CoA + HCO3- | first step in fatty acid biosynthesis | Rattus norvegicus | ADP + malonyl-CoA + phosphate | - |
? | |
ATP + acetyl-CoA + HCO3- | first step in fatty acid biosynthesis via fatty acid synthase type II, overview | Staphylococcus aureus | ADP + malonyl-CoA + phosphate | - |
? | |
ATP + acetyl-CoA + HCO3- | first step in fatty acid biosynthesis via fatty acid synthase type II, overview | Bacillus subtilis | ADP + malonyl-CoA + phosphate | - |
? | |
ATP + acetyl-CoA + HCO3- | first step in fatty acid biosynthesis via fatty acid synthase type II, overview | Escherichia coli | ADP + malonyl-CoA + phosphate | - |
? | |
ATP + acetyl-CoA + HCO3- | - |
Escherichia coli MG1655 | ADP + malonyl-CoA + phosphate | - |
? | |
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 | Comment | Organism |
---|---|---|
ACC | - |
Staphylococcus aureus |
ACC | - |
Bacillus subtilis |
ACC | - |
Escherichia coli |
ACC | - |
Rattus norvegicus |
pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
---|---|---|---|
7.4 | - |
assay at | Rattus norvegicus |
8 | - |
assay at | Staphylococcus aureus |
8 | - |
assay at | Bacillus subtilis |
8 | - |
assay at | Escherichia coli |
Cofactor | Comment | Organism | Structure |
---|---|---|---|
ATP | - |
Staphylococcus aureus | |
ATP | - |
Bacillus subtilis | |
ATP | - |
Escherichia coli | |
ATP | - |
Rattus norvegicus |
Ki Value [mM] | Ki Value maximum [mM] | Inhibitor | Comment | Organism | Structure |
---|---|---|---|---|---|
additional information | - |
additional information | inhibition kinetics | Staphylococcus aureus | |
additional information | - |
additional information | inhibition kinetics | Escherichia coli |
IC50 Value | IC50 Value Maximum | Comment | Organism | Inhibitor | Structure |
---|---|---|---|---|---|
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 | |
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 | |
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 | |
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 | |
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 | |
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 | |
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 | |
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 | |
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 | |
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 | |
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 | |
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 | |
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 |