Information on EC 6.2.1.2 - butyrate-CoA ligase

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The expected taxonomic range for this enzyme is: Eukaryota, Archaea, Bacteria

EC NUMBER
COMMENTARY hide
6.2.1.2
-
RECOMMENDED NAME
GeneOntology No.
butyrate-CoA ligase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
ATP + a carboxylate + CoA = AMP + diphosphate + an acyl-CoA
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Acid-thiol ligation
-
-
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
Butanoate metabolism
-
-
Metabolic pathways
-
-
methyl ketone biosynthesis (engineered)
-
-
SYSTEMATIC NAME
IUBMB Comments
butanoate:CoA ligase (AMP-forming)
Acts on acids from C4 to C11 and on the corresponding 3-hydroxy- and 2,3- or 3,4-unsaturated acids.
CAS REGISTRY NUMBER
COMMENTARY hide
9080-51-7
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
-
-
Manually annotated by BRENDA team
axenic strain, AX3, gene eloA
UniProt
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
UniProt
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
strain AHU 9417
-
-
Manually annotated by BRENDA team
strain AHU 9417
-
-
Manually annotated by BRENDA team
gene phl or pclA; gene phl
UniProt
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
ATP + 1-anthracenecarboxylic acid + CoA
AMP + diphosphate + anthracene-1-carboxyl-CoA
show the reaction diagram
-
2% of the activity with hexanoic acid
-
?
ATP + 1-naphthoic acid + CoA
AMP + diphosphate + 1-naphthoyl-CoA
show the reaction diagram
ATP + 1-naphthylacetic acid + CoA
AMP + diphosphate + 1-naphthyl-acetyl-CoA
show the reaction diagram
ATP + 1-naphthylacetic acid + CoA
AMP + diphosphate + 1-naphthylacetoyl-CoA
show the reaction diagram
ATP + 2-aminobenzoate + CoA
AMP + diphosphate + 2-aminobenzoyl-CoA
show the reaction diagram
-
1.4% of the activity with dodecanoate
-
?
ATP + 2-anthracenecarboxylic acid + CoA
AMP + diphosphate + anthracene-2-carboxyl-CoA
show the reaction diagram
-
16% of the activity with hexanoic acid
-
?
ATP + 2-methylbutyrate + CoA
AMP + diphosphate + 2-methylbutyryl-CoA
show the reaction diagram
ATP + 2-naphthylacetic acid + CoA
AMP + diphosphate + 2-naphthyl-acetyl-CoA
show the reaction diagram
ATP + 3,4-methylenedioxycinnamic acid + CoA
AMP + diphosphate + 3,4-methylenedioxy-cinnamoyl-CoA
show the reaction diagram
high activity
-
-
?
ATP + 3-aminobenzoate + CoA
AMP + diphosphate + 3-aminobenzoyl-CoA
show the reaction diagram
ATP + 3-chlorobenzoate + CoA
AMP + diphosphate + 3-chlorobenzoyl-CoA
show the reaction diagram
ATP + 3-ethoxycinnamic acid + CoA
AMP + diphosphate + 3-ethoxy-cinnamoyl-CoA
show the reaction diagram
high activity
-
-
?
ATP + 3-methoxybenzoate + CoA
AMP + diphosphate + 3-methoxybenzoyl-CoA
show the reaction diagram
ATP + 3-methoxycinnamic acid + CoA
AMP + diphosphate + 3-methoxy-cinnamoyl-CoA
show the reaction diagram
high activity
-
-
?
ATP + 3-methylbenzoate + CoA
AMP + diphosphate + 3-methylbenzoyl-CoA
show the reaction diagram
ATP + 3-nitrobenzoate + CoA
AMP + diphosphate + 3-nitrobenzoyl-CoA
show the reaction diagram
-
28% of the activity with benzoate
-
?
ATP + 4-aminobenzoate + CoA
AMP + diphosphate + 4-aminobenzoyl-CoA
show the reaction diagram
ATP + 4-chlorobenzoate + CoA
AMP + diphosphate + 4-chlorobenzoyl-CoA
show the reaction diagram
ATP + 4-heptylbenzoate + CoA
AMP + diphosphate + 4-heptylbenzoyl-CoA
show the reaction diagram
-
66% of the activity with hexanoic acid
-
?
ATP + 4-methoxybenzoate + CoA
AMP + diphosphate + 4-methoxybenzoyl-CoA
show the reaction diagram
ATP + 4-methylbenzoate + CoA
AMP + diphosphate + 4-methylbenzoyl-CoA
show the reaction diagram
ATP + 4-nitrobenzoate + CoA
AMP + diphosphate + 4-nitrobenzoyl-CoA
show the reaction diagram
-
29% of the activity with benzoate
-
?
ATP + a medium chain fatty acid or an aromatic acid or an arylacetic acid + CoA
?
show the reaction diagram
-
the enzyme catalyzes the first reaction of glycine conjugation, which is an important route of detoxification of many xenobiotic and endogenous carboxylic acids
-
-
-
ATP + arachidonic acid + CoA
AMP + diphosphate + arachidonoyl-CoA
show the reaction diagram
-
5.2% of the activity with dodecanoate
-
?
ATP + benzoate + CoA
AMP + diphosphate + benzoyl-CoA
show the reaction diagram
ATP + benzoic acid + CoA
AMP + diphosphate + benzoyl-CoA
show the reaction diagram
-
also active with several benzoic acids substituted at position 2, 3 or 4
-
-
-
ATP + butyrate + CoA
AMP + diphosphate + butyryl-CoA
show the reaction diagram
ATP + caproic acid + CoA
AMP + diphosphate + caproyl-CoA
show the reaction diagram
-
-
-
?
ATP + crotonate + CoA
AMP + diphosphate + crotonyl-CoA
show the reaction diagram
-
i.e. E-2-butenoate, 20% of the activity relative to butyrate
-
-
-
ATP + cyclohexanoic acid + CoA
AMP + diphosphate + cyclohexanoyl-CoA
show the reaction diagram
-
41% of the activity with hexanoic acid
-
?
ATP + decanoate + CoA
AMP + diphosphate + decanoyl-CoA
show the reaction diagram
ATP + dodecanoate + CoA
AMP + diphosphate + dodecanoyl-CoA
show the reaction diagram
ATP + heptanoate + CoA
AMP + diphosphate + heptanoyl-CoA
show the reaction diagram
ATP + hexanoate + CoA
AMP + diphosphate + hexanoyl-CoA
show the reaction diagram
ATP + indomethacin + CoA
AMP + diphosphate + ?
show the reaction diagram
ATP + isobutyrate + CoA
AMP + diphosphate + isobutyryl-CoA
show the reaction diagram
ATP + isopentanoate
AMP + diphosphate + isopentanoyl-CoA
show the reaction diagram
-
-
-
-
-
ATP + ketoprofen + CoA
ADP + diphosphate + ?
show the reaction diagram
ATP + L-(+)-3-hydroxybutyrate + CoA
?
show the reaction diagram
-
enzyme reesterifies CoA and L-(+)-3-hydroxybutyrate. It is required for the production of L-(+)-3-hydroxybutyrate in rat liver
-
-
-
ATP + L-(+)-3-hydroxybutyrate + CoA
AMP + diphosphate + L-(+)-3-hydroxybutyryl-CoA
show the reaction diagram
-
-
-
-
ATP + laurate + CoA
AMP + diphosphate + lauroyl-CoA
show the reaction diagram
-
12.6% of the activity with octanoate
-
?
ATP + linolenic acid + CoA
AMP + diphosphate + linolenoyl-CoA
show the reaction diagram
-
8.3% of the activity with dodecanoate
-
?
ATP + m-hydroxybenzoate + CoA
AMP + diphosphate + m-hydroxybenzoyl-CoA
show the reaction diagram
-
0.8% of the activity with dodecanoate
-
?
ATP + m-methoxybenzoate + CoA
AMP + diphosphate + m-methoxybenzoyl-CoA
show the reaction diagram
ATP + m-pentylbenzoate + CoA
AMP + diphosphate + m-pentylbenzoyl-CoA
show the reaction diagram
ATP + myristic acid + CoA
AMP + diphosphate + myristoyl-CoA
show the reaction diagram
-
-
-
?
ATP + octanoate + CoA
AMP + diphosphate + octanoyl-CoA
show the reaction diagram
ATP + p-methoxybenzoate + CoA
AMP + diphosphate + p-methoxybenzoyl-CoA
show the reaction diagram
ATP + p-pentylbenzoate + CoA
AMP + diphosphate + p-pentylbenzoyl-CoA
show the reaction diagram
ATP + pentanoate + CoA
AMP + diphosphate + pentanoyl-CoA
show the reaction diagram
ATP + phenoxyacetate + CoA
AMP + diphosphate + phenoxyacetyl-CoA
show the reaction diagram
i.e. POA, low activity
-
-
?
ATP + phenylacetate + CoA
AMP + diphosphate + phenylacetyl-CoA
show the reaction diagram
ATP + propionate + CoA
AMP + diphosphate + propionyl-CoA
show the reaction diagram
ATP + propionic acid + CoA
AMP + diphosphate + propionyl-CoA
show the reaction diagram
low activity
-
-
?
ATP + tetradecanoate + CoA
AMP + diphosphate + tetradecanoyl-CoA
show the reaction diagram
-
3.9% of the activity with dodecanoate
-
?
ATP + tranexamic acid + CoA
AMP + diphosphate + tranexoyl-CoA
show the reaction diagram
ATP + trans-4-coumaric acid + CoA
AMP + diphosphate + trans-4-coumaroyl-CoA
show the reaction diagram
-
-
-
?
ATP + trans-cinnamic acid + CoA
AMP + diphosphate + trans-cinnamoyl-CoA
show the reaction diagram
1000fold higher activity compared to PAA
-
-
?
ATP + tridecanoate + CoA
AMP + diphosphate + tridecanoyl-CoA
show the reaction diagram
-
15% of the activity with dodecanoate
-
?
ATP + valerate + CoA
AMP + diphosphate + valeryl-CoA
show the reaction diagram
-
9.9% of the activity with octanoate
-
?
ATP + valproate + CoA
ADP + diphosphate + valproyl-CoA
show the reaction diagram
ATP + valproic acid + CoA
AMP + diphosphate + valproyl-CoA
show the reaction diagram
CTP + butyrate + CoA
CMP + diphosphate + butyryl-CoA
show the reaction diagram
-
slight activity
-
-
-
ITP + butyrate + CoA
IMP + diphosphate + butyryl-CoA
show the reaction diagram
-
slight activity
-
-
-
additional information
?
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
ATP + a medium chain fatty acid or an aromatic acid or an arylacetic acid + CoA
?
show the reaction diagram
-
the enzyme catalyzes the first reaction of glycine conjugation, which is an important route of detoxification of many xenobiotic and endogenous carboxylic acids
-
-
-
ATP + L-(+)-3-hydroxybutyrate + CoA
?
show the reaction diagram
-
enzyme reesterifies CoA and L-(+)-3-hydroxybutyrate. It is required for the production of L-(+)-3-hydroxybutyrate in rat liver
-
-
-
ATP + phenylacetate + CoA
AMP + diphosphate + phenylacetyl-CoA
show the reaction diagram
O74725
enzymatic activation of phenylacetic acid to phenylacetyl-CoA is an important step in the biosynthesis of the beta-lactam antibiotic penicillin G by the fungus Penicillium chrysogenum, CoA esters of PAA and phenoxyacetic acid act as acyl donor in the exchange of the aminoadipyl side chain of isopenicillin N to produce penicillin G or penicillin V
-
-
?
additional information
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Ca2+
-
can replace Mg2+ in activation with 47% of the efficiency, Km: 0.14 mM
NaCl
stabilizes at 200 mM
Rb+
-
can replace K+ in activation with 81% efficiency, Km: 2.4 mM
additional information
-
no differential response to monovalent cations
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(NH4)2SO4
-
-
2-hydroxydodecanoic acid
2-Hydroxynaphthoic acid
2-Hydroxyoctanoic acid
-
competitive with respect to hexanoate
2-hydroxyphenylacetic acid
-
-
4-methylsalicylic acid
-
competitive with respect to hexanoate
5,5'-dithiobis(2-nitrobenzoate)
-
-
Benzoate
-
competitive inhibitor of butyrate
benzoyl-CoA
-
product inhibitor
Butyrate
-
competitive inhibitor of benzoate
Butyryl-CoA
cyclohexane carboxylate
-
-
diflunisal
diphosphate
dithiothreitol
-
-
enoxacin
felbinac
-
inhibits activity with hexanoic acid, IC50: 0.025 mM
Hg(CH3COO)2
-
-
iodoacetamide
-
-
Mercury compounds
-
-
-
Nalidixic acid
Octanoate
-
valproyl-AMP synthesis
ofloxacin
-
potent, mixed-type inhibition
ofloxacine
p-chloromercuribenzoate
salicylic acid
Silver compounds
-
-
-
sulfhydryl reagents
-
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
bovine serum albumin
iodoacetate
-
activates up to 80% by low concentrations, in a 1:1 molar ratio with the 40000 MW species of the enzyme
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
8.92
2-methylbutyrate
pH 7.5, 55C
0.036 - 4.21
ATP
0.007
Benzoate
-
-
0.14 - 4.2
Butyrate
0.02 - 4.09
CoA
1.775
Decanoate
-
-
0.02
dodecanoate
-
-
1.6
Isobutyrate
-
-
0.47
Isopentanoate
-
-
4
L-(+)-3-hydroxybutyrate
-
-
0.97
MgATP2-
-
-
0.001
myristic acid
below, pH 8.5, 30C, recombinant enzyme
0.108 - 0.285
Octanoate
0.38
pentanoate
-
-
2.1
Phenoxyacetate
pH 8.5, 30C, recombinant enzyme
5.2 - 6.1
phenylacetate
pH 8.5, 30C, recombinant enzyme
3.3
Propionate
-
-
80
Propionic acid
pH 8.5, 30C, recombinant enzyme
0.19
trans-cinnamic acid
pH 8.5, 30C, recombinant enzyme
additional information
additional information
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1.58
2-methylbutyrate
Methanosarcina acetivorans
Q8TLW1
pH 7.5, 55C
1.7 - 42.9
ATP
1.5 - 60.5
CoA
12
Phenoxyacetate
Penicillium chrysogenum
O74725
pH 8.5, 30C, recombinant enzyme
1.3 - 1.9
phenylacetate
Penicillium chrysogenum
O74725
pH 8.5, 30C, recombinant enzyme
41.2
trans-cinnamic acid
Penicillium chrysogenum
O74725
pH 8.5, 30C, recombinant enzyme
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.18
2-methylbutyrate
Methanosarcina acetivorans
Q8TLW1
pH 7.5, 55C
12748
0.46
ATP
Methanosarcina acetivorans
Q8TLW1
pH 7.5, 55C
4
0.53
CoA
Methanosarcina acetivorans
Q8TLW1
pH 7.5, 55C
18
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0044 - 0.015
2-hydroxydodecanoic acid
0.0134
2-Hydroxynaphthoic acid
-
pH 8.5, 37C
0.37
2-hydroxyphenylacetic acid
-
pH 8.5
0.17
cyclohexane carboxylate
-
reaction with butyrate as substrate
0.0006 - 0.0008
diflunisal
0.0237
enoxacin
-
-
0.0123 - 0.0124
Nalidixic acid
0.0382
ofloxacine
-
-
0.0196
salicylic acid
-
pH 8.5, 37C
additional information
additional information
inhibition kinetics
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.025
felbinac
Mus musculus
-
inhibits activity with hexanoic acid, IC50: 0.025 mM
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.02
purified recombinant enzyme
0.023
-
cell extract, with 0.001 mM hexanoic acid as a substrate in 0.2 M Tris-HCl buffer (pH 8.5)
3.3
-
-
3.718
-
-
4.14
-
after 180fold purification, with 0.001 mM hexanoic acid as a substrate in 0.2 M Tris-HCl buffer (pH 8.5)
4.15
-
-
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7
-
reaction with butyrate as substrate
8.6
-
reaction with octanoate as substrate
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6.8 - 8
-
increase of activity when the pH increases from 6.8 to 8
8.5 - 10
-
8.5: 53% of maximal activity, 10.0: 80% of maximal activity, a pH-optimum is not observed
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
46500
-
gel filtration
64000
-
monomeric form of enzyme, gel filtration
65000
-
SDS-PAGE
130000
-
dimeric form of enzyme, gel filtration
142000
-
disc gel electrophoresis
145000
-
gel filtration
260000
-
tetrameric form of enzyme, gel filtration
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
monomer
-
1 * 65000, the enzyme exists in monomeric, dimeric and tertameric form, SDS-PAGE
tetramer
additional information
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
4 - 9
-
37C, 15 min, stable
669
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
37
-
pH 4.0-9.0, 15 min, stable
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
presence of 200 mM NaCl is essential for the stability of the enzyme and storage or conversions in buffer lacking NaCl resulted in rapid loss of activity
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-20C, purified recobnant protein in TANG buffer, several months without significant loss of activity
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
enzyme form HXM-A and HXM-B
-
partial
-
recombinant C-terminally His6-tagged maltose binding protein fusion from Escherichia coli by nickel affinity chromatography, the MBP is cleaved off by factor Xa, imidazole is eliminated by gel filtration, recombinant His-tagged mutants
Sephadex G-25 gel filtration, DEAE-Sepharose column chromatography, and hydroxylapatite column chromatography
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
a plasmid with a His-tagged fusion protein is constructed for expression in Escherichia coli
-
expressed in Escherichia coli DH5alpha and BL21(DE) cells
-
expression of HXM-A in COS cells
-
gene eloA, phylogenetic analysis, expression of the putative Dictyostelium discoideum eloA cDNA in Saccharomces cerevisiae
gene phl, sequence analysis, functional expression as C-terminally His6-tagged maltose binding protein fusion in Escherichia coli, expression of His-tagged mutants
heterologous production in Escherichia coli
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
F307A
site-directed mutagenesis, the mutant shows an increased Km for phenoxyacetic acid compared to the wild-type enzyme
F335A
site-directed mutagenesis, the mutant shows an increased Km for phenoxyacetic acid compared to the wild-type enzyme
V270A
site-directed mutagenesis, the mutant activity is similar to the wild-type enzyme
V370A
site-directed mutagenesis, the mutant activity is similar to the wild-type enzyme
Y267A
site-directed mutagenesis, the mutant shows an increased Km for phenoxyacetic acid compared to the wild-type enzyme
additional information
construction of mutants with substrate binding pocket residues exchanged for alanine, the mutants show altered kinetics, overview
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
-
involvement of the MACS2 Leu513Ser polymorphism in the development of the metabolic syndrome
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