Information on EC 5.1.99.1 - Methylmalonyl-CoA epimerase

New: Word Map on EC 5.1.99.1
Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
Specify your search results
Mark a special word or phrase in this record:
Select one or more organisms in this record:
Show additional data
Do not include text mining results
Include (text mining) results (more...)
Include results (AMENDA + additional results, but less precise; more...)


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

EC NUMBER
COMMENTARY
5.1.99.1
-
RECOMMENDED NAME
GeneOntology No.
Methylmalonyl-CoA epimerase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
(R)-methylmalonyl-CoA = (S)-methylmalonyl-CoA
show the reaction diagram
-
-
-
-
(R)-methylmalonyl-CoA = (S)-methylmalonyl-CoA
show the reaction diagram
with (2R)-methylmalonyl-CoA as substrate: two enzyme bases act respectively as proton donor and acceptor, the release of product is slow, and the reprotonation step on the enzyme is reversible, without leading to isotopic exchange with the solvent
-
(R)-methylmalonyl-CoA = (S)-methylmalonyl-CoA
show the reaction diagram
mechanism involving loss of the alpha-hydrogen atom with subsequent incorporation of a proton from the medium
-
(R)-methylmalonyl-CoA = (S)-methylmalonyl-CoA
show the reaction diagram
enzyme acts to labilize the proton on the tertiary carbon atom of methylmalonyl-CoA, and thus causes a rapid exchange of this proton with those of water
-
(R)-methylmalonyl-CoA = (S)-methylmalonyl-CoA
show the reaction diagram
two enzyme bases are involved in catalysis. One base removes the proton from the substrate, the second provides the new proton. There is no fast isotopic exchange between enzyme-bound intermediates and solvent protons
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
epimerization
-
-
-
-
epimerization
-
-
epimerization
A1IVX2
-
epimerization
Q96PE7
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
3-hydroxypropanoate cycle
-
-
3-hydroxypropanoate/4-hydroxybutanate cycle
-
-
anaerobic energy metabolism (invertebrates, mitochondrial)
-
-
Carbon fixation pathways in prokaryotes
-
-
CO2 fixation in Crenarchaeota
-
-
ethylmalonyl-CoA pathway
-
-
Glyoxylate and dicarboxylate metabolism
-
-
Metabolic pathways
-
-
methylaspartate cycle
-
-
Microbial metabolism in diverse environments
-
-
Propanoate metabolism
-
-
propanoyl CoA degradation I
-
-
propionate fermentation
-
-
pyruvate fermentation to propanoate I
-
-
Valine, leucine and isoleucine degradation
-
-
SYSTEMATIC NAME
IUBMB Comments
methylmalonyl-CoA 2-epimerase
-
SYNONYMS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
DL-Methylmalonyl-CoA racemase
-
-
-
-
DL-Methylmalonyl-coenzyme A racemase
-
-
-
-
MCE
Q96PE7
-
MCEE
Q96PE7
methylmalonyl-CoA 2-epimerase gene
Methylmalonyl coenzyme A racemase
-
-
-
-
methylmalonyl-CoA 2-epimerase
-
-
methylmalonyl-CoA 2-epimerase
Q96PE7
-
methylmalonyl-CoA 2-epimerase
A1IVX2
-
methylmalonyl-CoA 2-racemase
Q96PE7
-
methylmalonyl-CoA epimerase
-
-
methylmalonyl-CoA epimerase
Q8RCQ6
-
methylmalonyl-CoA epimerase
Q96PE7
-
methylmalonyl-CoA epimerase
A4YEG2
-
methylmalonyl-CoA epimerase
A4YEG2
-
-
methylmalonyl-CoA epimerase
A1IVX2
-
Methylmalonyl-CoA racemase
-
-
-
-
methylmalonyl-coenzyme A epimerase
A4YEG2
-
methylmalonyl-coenzyme A epimerase
A4YEG2
-
-
mm-CoA epimerase
-
-
Msed_0639
A4YEG2
locus name
Msed_0639
A4YEG2
locus name
-
Racemase, methylmalonyl coenzyme A
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
9024-03-7
-
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
physiological function
Q8RCQ6
second step in the pathway responsible for the degradation of branched amino acids and odd chain fatty acids, MMCE participated in autotrophic CO2 fixation via the 3-hydroxypropionate pathway, in propionate fermentation, the regeneration of glyoxylate and in the biosynthesis of polyketide antibiotics
physiological function
A4YEG2
methylmalonyl-CoA epimerase and methylmalonyl-CoA mutase are responsible for producing succinyl-CoA from (S)-methylmalonyl-CoA. Succinyl-CoA is an intermediate connecting the 3-hydroxypropionate/4-hydroxybutyrate cycle and general carbon metabolism. Methylmalonyl-CoA epimerase and methylmalonyl-CoA mutase may also be involved in degradation of propionate and branched-chain amino acids (valine, isoleucine, methionine). The enzyme has a role in CO2 fixation, the enzyme is involved in the 3-hydroxypropionate/4-hydroxybutyrate carbon fixation pathway
physiological function
-
methylmalonyl-CoA epimerase and methylmalonyl-CoA mutase are responsible for producing succinyl-CoA from (S)-methylmalonyl-CoA. Succinyl-CoA is an intermediate connecting the 3-hydroxypropionate/4-hydroxybutyrate cycle and general carbon metabolism. Methylmalonyl-CoA epimerase and methylmalonyl-CoA mutase may also be involved in degradation of propionate and branched-chain amino acids (valine, isoleucine, methionine). The enzyme has a role in CO2 fixation, the enzyme is involved in the 3-hydroxypropionate/4-hydroxybutyrate carbon fixation pathway
-
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
(2R)-methylmalonyl-CoA
(2S)-methylmalonyl-CoA
show the reaction diagram
-
-
-
-
r
(2S)-ethylmalonyl-CoA
(2R)-ethylmalonyl-CoA
show the reaction diagram
Q3IZP4
-
-
-
?
(R)-2-Methyl-3-oxopropanoyl-CoA
(S)-2-Methyl-3-oxopropanoyl-CoA
show the reaction diagram
-
-
-
-
(R)-2-Methyl-3-oxopropanoyl-CoA
(S)-2-Methyl-3-oxopropanoyl-CoA
show the reaction diagram
-
-
-
-
(R)-2-Methyl-3-oxopropanoyl-CoA
(S)-2-Methyl-3-oxopropanoyl-CoA
show the reaction diagram
-
-
-
-
(R)-2-Methyl-3-oxopropanoyl-CoA
(S)-2-Methyl-3-oxopropanoyl-CoA
show the reaction diagram
-
-
-
-
(R)-2-Methyl-3-oxopropanoyl-CoA
(S)-2-Methyl-3-oxopropanoyl-CoA
show the reaction diagram
-
-
-
-
(R)-2-Methyl-3-oxopropanoyl-CoA
(S)-2-Methyl-3-oxopropanoyl-CoA
show the reaction diagram
-
-
-
-
(R)-2-Methyl-3-oxopropanoyl-CoA
(S)-2-Methyl-3-oxopropanoyl-CoA
show the reaction diagram
-
-
-
-
(R)-2-Methyl-3-oxopropanoyl-CoA
(S)-2-Methyl-3-oxopropanoyl-CoA
show the reaction diagram
-
-
-
-
(R)-2-Methyl-3-oxopropanoyl-CoA
(S)-2-Methyl-3-oxopropanoyl-CoA
show the reaction diagram
-
-
-
-
(R)-2-Methyl-3-oxopropanoyl-CoA
(S)-2-Methyl-3-oxopropanoyl-CoA
show the reaction diagram
-
r
-
-
(R)-methylmalonyl-CoA
(S)-methylmalonyl-CoA
show the reaction diagram
-
-
-
-
?
(R)-methylmalonyl-CoA
(S)-methylmalonyl-CoA
show the reaction diagram
-
-
-
?
(R)-methylmalonyl-CoA
(S)-methylmalonyl-CoA
show the reaction diagram
-
-
-
-
?
(R)-methylmalonyl-CoA
(S)-methylmalonyl-CoA
show the reaction diagram
-
-
-
?
(R)-methylmalonyl-CoA
(S)-methylmalonyl-CoA
show the reaction diagram
Q96PE7
-
-
-
?
(R)-methylmalonyl-CoA
(S)-methylmalonyl-CoA
show the reaction diagram
-
-
-
-
?
(R)-methylmalonyl-CoA
(S)-methylmalonyl-CoA
show the reaction diagram
Q8RCQ6
-
-
-
r
(R)-methylmalonyl-CoA
(S)-methylmalonyl-CoA
show the reaction diagram
A1IVX2
mm-CoA
detection by GCMS
-
?
(S)-methylmalonyl-CoA
(R)-methylmalonyl-CoA
show the reaction diagram
Q3IZP4
-
-
-
?
(S)-methylmalonyl-CoA
(R)-methylmalonyl-CoA
show the reaction diagram
A4YEG2
the enzyme is involved in the 3-hydroxypropionate/4-hydroxybutyrate carbon fixation pathway
-
-
?
(S)-methylmalonyl-CoA
(R)-methylmalonyl-CoA
show the reaction diagram
A4YEG2
the enzyme is involved in the 3-hydroxypropionate/4-hydroxybutyrate carbon fixation pathway
-
-
?
additional information
?
-
-
enzyme is involved in the flow of DL-methylmalonyl-CoA to L-methylmalonyl-CoA
-
-
-
additional information
?
-
-
essential enzyme in the breakdown of odd-numbered fatty acids and of the amino acids valine, isoleucine, and methionine
-
?
additional information
?
-
Q3IZP4
enzyme catalyzes the transformation of ethylmalonyl-CoA to methylsuccinyl-CoA in combination with ethylmalonyl-CoA mutase, in a ethylmalonyl-CoA dependent acyl-CoA pathway for acetate assimilation
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
(R)-methylmalonyl-CoA
(S)-methylmalonyl-CoA
show the reaction diagram
-
-
-
-
?
(R)-methylmalonyl-CoA
(S)-methylmalonyl-CoA
show the reaction diagram
Q8RCQ6
-
-
-
r
(S)-methylmalonyl-CoA
(R)-methylmalonyl-CoA
show the reaction diagram
A4YEG2
the enzyme is involved in the 3-hydroxypropionate/4-hydroxybutyrate carbon fixation pathway
-
-
?
(S)-methylmalonyl-CoA
(R)-methylmalonyl-CoA
show the reaction diagram
A4YEG2
the enzyme is involved in the 3-hydroxypropionate/4-hydroxybutyrate carbon fixation pathway
-
-
?
additional information
?
-
-
enzyme is involved in the flow of DL-methylmalonyl-CoA to L-methylmalonyl-CoA
-
-
-
additional information
?
-
-
essential enzyme in the breakdown of odd-numbered fatty acids and of the amino acids valine, isoleucine, and methionine
-
?
additional information
?
-
Q3IZP4
enzyme catalyzes the transformation of ethylmalonyl-CoA to methylsuccinyl-CoA in combination with ethylmalonyl-CoA mutase, in a ethylmalonyl-CoA dependent acyl-CoA pathway for acetate assimilation
-
-
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Co2+
-
most potent activator, Km: 0.0002 mM, binds 2 mol Co2+ per mol of racemase
Co2+
-
increases activity
Co2+
Q3IZP4
0.4 mM, 4fold increase in activity. Presence of Co2+ restores activity after incubation with EDTA
Co2+
Q8RCQ6
enzyme is metal-dependent enzyme, in the active site, metal binding site binds the coenzyme Co2+
Co2+
A4YEG2
activates; the enzyme is activated by divalent cations (Ni2+, Co2+, and Mg2+)
Co3+
-
lower level of activation than Co2+ at higher concentrations
Fe2+
-
lower level of activation than Co2+ at higher concentrations
Mg2+
A4YEG2
activates; the enzyme is activated by divalent cations (Ni2+, Co2+, and Mg2+)
Mn2+
-
increases activity to a smaller extent than Co2+
Mn2+
-
lower level of activation than Co2+ at higher concentrations
Ni2+
-
increases activity to a smaller extent than Co2+
Ni2+
A4YEG2
activates; the enzyme is activated by divalent cations (Ni2+, Co2+, and Mg2+)
Zn2+
-
increases activity to a smaller extent than Co2+
Mn2+
Q3IZP4
presence of Mn2+ restores activity after incubation with EDTA
additional information
-
enzyme does not require tightly bound metal ions for activity, they are not released even after extensive dialysis at pH 2.4
additional information
-
His12, Gln65, His91 and Glu141 provide a binding site for a divalent metal ion, as shown by binding of Co2+
additional information
Q3IZP4
no activation of enzyme with Mg2+, Ni2+
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
acetyl-CoA
-
-
Butyryl-CoA
-
-
EDTA
-
reactivation by Co2+
EDTA
Q3IZP4
2 mM, complete loss of activity
glutaryl-CoA
-
-
Heptanoyl-CoA
-
-
malonyl-CoA
-
-
Octanoyl-CoA
-
-
propionyl-CoA
-
-
succinyl-CoA
-
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.04
(2S)-ethylmalonyl-CoA
Q3IZP4
-
0.08
(S)-methylmalonyl-CoA
Q3IZP4
-
0.1
DL-methylmalonyl-CoA
-
-
0.079
methylmalonyl-CoA
-
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
4170
DL-methylmalonyl-CoA
-
-
240
methylmalonyl-CoA
-
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.35
-
-
218
A4YEG2
75C, pH not specified in the publication; purified recombinant enzyme, pH 7.0, 75C
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7
A4YEG2
assay at
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
5 - 9
-
50% of maximal activity at pH 5.5 and 8.5
5.5 - 8.5
-
50% of maximal activity at pH 5.5 and 8.5
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
75
A4YEG2
assay at
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
additional information
A4YEG2
transcriptomic analyses of Metallosphaera sedula grown under autotrophic versus heterotrophic conditions, overview. MCE expression is significantly upregulated under autotrophic compared to heterotrophic growth conditions
Manually annotated by BRENDA team
additional information
-
transcriptomic analyses of Metallosphaera sedula grown under autotrophic versus heterotrophic conditions, overview. MCE expression is significantly upregulated under autotrophic compared to heterotrophic growth conditions
-
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
29000
-
low speed sedimentation without reaching equilibrium
2438
32000
-
gel filtration
2434, 2442
32100
A4YEG2
gel filtration; recombinant His-tagged enzyme, gel filtration
726729
33000 - 35000
-
gel filtration, sedimentation equilibrium studies
2437
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
-
2 * 16000, subunits not connected by disulfide bonds, SDS-PAGE in presence and absence of 2-mercaptoethanol
dimer
-
2 * 17000, SDS-PAGE in presence of 2-mercaptoethanol
dimer
-
2 * 31700
homodimer
A4YEG2
2 * 20000, SDS-PAGE, 2 * 20000, recombinant His-tagged enzyme, SDS-PAGE
homodimer
-
2 * 20000, SDS-PAGE, 2 * 20000, recombinant His-tagged enzyme, SDS-PAGE
-
additional information
A4YEG2
the putative three-dimensional structure of the enzyme is modeled using hypothetical protein BH1468, PDB ID 3OA4
additional information
-
the putative three-dimensional structure of the enzyme is modeled using hypothetical protein BH1468, PDB ID 3OA4
-
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
at 2.0 A resolutionm, crystals of recombinant enzyme are grown at 20C using the hanging-drop, vapor-diffusion method, drops consisted of 2 microl of protein solution and 2 microl of mother liquor (0.1 M citric acid, pH 2.6, 1.6 M (NH4)2SO4), crystals are obtained after 7-8 days growth, native and derivative crystals are soaked in 2 M Li2SO4
Q8RCQ6
crystallization of native, Co2+-substituted and SeMet-substituted enzyme by hanging-drop vapour-diffusion method
-
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
100
-
33% loss of activity after 1 min, 50% loss of activity after 5 min
2438
100
-
60 min, stable
649408
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
loss of activity after repeated freezing and thawing
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-15C, fairly stable
-
-20C, pH 8.5, indefinitely stable
-
-20C, stable for at least 3 months
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
recombinant MCE-1
-
lysate is clarified by centrifugation and purified by passage through a nickel-affinity column, and a further purification step is performed by gel filtration
Q8RCQ6
; recombinant N-terminally His-tagged enzyme from Escherichia coli strain Rosetta 2 (DE3) by nickel affinity chromatography
A4YEG2
recombinant enzyme
Q3IZP4
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expression in Escherichia coli
-
in a RNAi vector in Escherichia coli
-
recombinant protein is expressed in BL21(DE3) Escherichia coli cells
Q8RCQ6
expression in Escherichia coli; gene Msed_0639, DNA and amino acid sequence determination, phylogenetic tree, recombinant expression of N-terminally His-tagged enzyme in Escherichia coli strain Rosetta 2 (DE3)
A4YEG2
expression in Escherichia coli as native enzyme and as selenomethionine derivative
-
high level expression in Escherichia coli
-
expression in Eschserichia coli
Q3IZP4
expression in Pseudomonas putida, KT2440
A1IVX2
expressed in Escherichia coli BL21(DE3) cells
-
gene epi, functional exxpression in Pseudomonas putida strain KT2440, coexpression with the methylmalonyl-CoA mutase from Escherichia coli leading to production of (2S)-methylmalonyl-CoA in the recombinant strain
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
expression of the gene is significantly upregulated under autotrophic compared to heterotrophic growth conditions, implying a role in CO2 fixation
A4YEG2
the enzyme expression is significantly upregulated under autotrophic compared to heterotrophic growth conditions
A4YEG2
expression of the gene is significantly upregulated under autotrophic compared to heterotrophic growth conditions, implying a role in CO2 fixation
-
-
the enzyme expression is significantly upregulated under autotrophic compared to heterotrophic growth conditions
-
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
-
as model to study human methylmalonic aciduria, deletion of the mce gene results in a 80% decreased incorporation of propionate into macromolecules and induces an accumulation of methylmalonic acid
medicine
-
point mutation in the methylmalonyl-CoA 2-epimerase gene (C139T) and an insertion polymorphism 41-160-161insT causes methylmalonic aciduria in patients, inhibition of the enzyme by siRNAs in HeLa cells reduces the synthesis of macromolecules
medicine
-
point mutation in the methylmalonyl-CoA 2-epimerase gene (C139T) results in an early termination signal and causes methylmalonic aciduria in a patient
analysis
-
a simple direct assay for DL-methylmalonyl-coenzyme A racemase which is based on the fact that the proton on C-2 of methylmalonyl-CoA is replaced by a proton in the medium during racemization
synthesis
A1IVX2
production of polyketides like myxothiazol requiring methylmalonyl-CoA as an extender unit