Information on EC 5.4.99.2 - Methylmalonyl-CoA mutase

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

EC NUMBER
COMMENTARY
5.4.99.2
-
RECOMMENDED NAME
GeneOntology No.
Methylmalonyl-CoA mutase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
(R)-methylmalonyl-CoA = succinyl-CoA
show the reaction diagram
-
-
-
-
(R)-methylmalonyl-CoA = succinyl-CoA
show the reaction diagram
mechanism
-
(R)-methylmalonyl-CoA = succinyl-CoA
show the reaction diagram
evidence for radical intermediates
-
(R)-methylmalonyl-CoA = succinyl-CoA
show the reaction diagram
mechanism
-
(R)-methylmalonyl-CoA = succinyl-CoA
show the reaction diagram
ONIOM calculations based on protein structure. Homolytic Co-C5 bond cleavage in the 5-deoxyadenosylcobalamin cofactor is a stepwise process in which conformational changens in the 5-deoxyadenosine moiety proceed the actual homolysis step. The movement of the deoxyadenosine moity during homolysis positions the resulting 5-deoxyadenosyl radical for the subsequent hydrogen atom transfer from the substrate
-
(R)-methylmalonyl-CoA = succinyl-CoA
show the reaction diagram
intrinsic hydrogen isotope effect is 51 due to multidimensional tunneling. Corner-cutting tunneling decreases the distance over which the system tunnels without a comparable increase in either the effective potential barrier or the effective mass for tunneling
-
REACTION TYPE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
group transfer
-
-
intramolecular
-
isomerization
-
-
-
-
PATHWAY
KEGG Link
MetaCyc Link
3-hydroxypropionate cycle
-
3-hydroxypropionate/4-hydroxybutyrate cycle
-
anaerobic energy metabolism (invertebrates, mitochondrial)
-
Carbon fixation pathways in prokaryotes
-
conversion of succinate to propionate
-
Glyoxylate and dicarboxylate metabolism
-
Metabolic pathways
-
methylaspartate cycle
-
Microbial metabolism in diverse environments
-
Propanoate metabolism
-
propionyl CoA degradation
-
pyruvate fermentation to propionate I
-
Valine, leucine and isoleucine degradation
-
SYSTEMATIC NAME
IUBMB Comments
(R)-methylmalonyl-CoA CoA-carbonylmutase
Requires a cobamide coenzyme.
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
(R)-2-methyl-3-oxopropanoyl-CoA CoA-carbonylmutase
-
-
-
-
(S)-Methylmalonyl-CoA mutase
-
-
-
-
L-methylmalonyl-co-enzyme-A mutase
-
-
L-methylmalonyl-CoA mutase
-
-
MCB-beta
-
-
-
-
MCM
-
-
-
-
MCM
P22033
-
MCM
Streptomyces clavuligerus CKD1119
-
-
-
MCM
-
-
MCM
Q8MI68
-
MCM-alpha
-
-
-
-
MCM-beta
-
-
-
-
Methylmalonyl CoA mutase
-
-
-
-
Methylmalonyl coenzyme A carbonylmutase
-
-
-
-
Methylmalonyl coenzyme A mutase
-
-
-
-
Methylmalonyl coenzyme A mutase
-
-
methylmalonyl-CoA mutase
Q8F222
-
methylmalonyl-CoA mutase
Q84FZ1
-
methylmalonyl-CoA mutase
P11653
-
methylmalonyl-CoA mutase
Q8Y2U5
-
methylmalonyl-CoA mutase
-
-
methylmalonyl-CoA mutase
-
-
Methylmalonyl-CoA-carbonyl mutase
-
-
-
-
MuT
P22033
-
Mutase, methylmalonyl coenzyme A
-
-
-
-
sleeping beauty mutase
-
-
CAS REGISTRY NUMBER
COMMENTARY
9023-90-9
-
ORGANISM
COMMENTARY
LITERATURE
SEQUENCE CODE
SEQUENCE DB
SOURCE
Baby hamster kidney fibroblast like cells
-
-
Manually annotated by BRENDA team
strain BL21
-
-
Manually annotated by BRENDA team
strain Z
Uniprot
Manually annotated by BRENDA team
Euglena gracilis Z
strain Z
Uniprot
Manually annotated by BRENDA team
expressed in Saccharomyces cerevisiae
-
-
Manually annotated by BRENDA team
alpha subunit
SwissProt
Manually annotated by BRENDA team
strain H37Rv (ATCC 25618)
-
-
Manually annotated by BRENDA team
strain CKD1119
-
-
Manually annotated by BRENDA team
Streptomyces clavuligerus CKD1119
strain CKD1119
-
-
Manually annotated by BRENDA team
beta subunit
SwissProt
Manually annotated by BRENDA team
additional information
no activity in Solanum tuberosum
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
physiological function
-
the MCM pathway plays a key role in increasing the methylmalonyl-CoA pool for FK506 (tacrolimus) biosynthesis in Streptomyces clavuligerus CKD1119
physiological function
-
methylmalonyl-CoA mutase (MUT) expression influences the risk of acquiring Mycobacterium bovis infection and developing bovine tuberculosis. Genetically-defined higher host MUT expression levels result in lower serum cholesterol concentration and tissue deposits that increase the protective immune response to Mycobacterium bovis, thus resulting in resistance to bovine tuberculosis and better response to Mycobacterium bovis bacilli Calmette-Guerin vaccination
physiological function
Streptomyces clavuligerus CKD1119
-
the MCM pathway plays a key role in increasing the methylmalonyl-CoA pool for FK506 (tacrolimus) biosynthesis in Streptomyces clavuligerus CKD1119
-
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
(R)-2-Methyl-3-oxopropanoyl-CoA
?
show the reaction diagram
-
-
-
-
-
(R)-2-Methyl-3-oxopropanoyl-CoA
?
show the reaction diagram
-
-
-
-
-
(R)-2-Methyl-3-oxopropanoyl-CoA
?
show the reaction diagram
-
-
-
-
-
(R)-2-Methyl-3-oxopropanoyl-CoA
?
show the reaction diagram
-
key position in metabolism of propionic acid
-
-
-
(R)-2-Methylmalonyl-CoA
Succinyl-CoA
show the reaction diagram
-
-
-
-
(R)-2-Methylmalonyl-CoA
Succinyl-CoA
show the reaction diagram
-
-
-
?
(R)-2-Methylmalonyl-CoA
Succinyl-CoA
show the reaction diagram
-
-
-
-
(R)-2-Methylmalonyl-CoA
Succinyl-CoA
show the reaction diagram
-
-
-
-
?
(R)-2-Methylmalonyl-CoA
Succinyl-CoA
show the reaction diagram
-
-
-
-
(R)-2-Methylmalonyl-CoA
Succinyl-CoA
show the reaction diagram
-
-
-
-
(R)-2-Methylmalonyl-CoA
Succinyl-CoA
show the reaction diagram
-
-
-
-
(R)-2-Methylmalonyl-CoA
Succinyl-CoA
show the reaction diagram
-
-
-
-
(R)-2-Methylmalonyl-CoA
Succinyl-CoA
show the reaction diagram
-
-
-
-
(R)-2-Methylmalonyl-CoA
Succinyl-CoA
show the reaction diagram
-
-
-
-
(R)-2-Methylmalonyl-CoA
Succinyl-CoA
show the reaction diagram
-
-
-
-
?
(R)-2-Methylmalonyl-CoA
Succinyl-CoA
show the reaction diagram
-
-
-
-
?
(R)-2-Methylmalonyl-CoA
Succinyl-CoA
show the reaction diagram
-
-
-
-
?
(R)-2-Methylmalonyl-CoA
Succinyl-CoA
show the reaction diagram
-
-
-
-
(R)-2-Methylmalonyl-CoA
Succinyl-CoA
show the reaction diagram
B7XBM0, -
-
-
-
r
(R)-2-Methylmalonyl-CoA
Succinyl-CoA
show the reaction diagram
-
-
-
-
(R)-2-Methylmalonyl-CoA
Succinyl-CoA
show the reaction diagram
-
-
-
-
(R)-2-Methylmalonyl-CoA
Succinyl-CoA
show the reaction diagram
-
-
-
-
?
(R)-2-Methylmalonyl-CoA
Succinyl-CoA
show the reaction diagram
-
-
-
-
(R)-2-Methylmalonyl-CoA
Succinyl-CoA
show the reaction diagram
-
-
-
-
(R)-2-Methylmalonyl-CoA
Succinyl-CoA
show the reaction diagram
-
-
-
-
(R)-2-Methylmalonyl-CoA
Succinyl-CoA
show the reaction diagram
-
-
-
-
(R)-2-Methylmalonyl-CoA
Succinyl-CoA
show the reaction diagram
-
-
-
-
(R)-2-Methylmalonyl-CoA
Succinyl-CoA
show the reaction diagram
-
-
-
-
(R)-2-Methylmalonyl-CoA
Succinyl-CoA
show the reaction diagram
-
-
-
-
(R)-2-Methylmalonyl-CoA
Succinyl-CoA
show the reaction diagram
-
-
-
-
(R)-2-Methylmalonyl-CoA
Succinyl-CoA
show the reaction diagram
-
-
-
-
(R)-2-Methylmalonyl-CoA
Succinyl-CoA
show the reaction diagram
-
-
-
-
(R)-2-Methylmalonyl-CoA
Succinyl-CoA
show the reaction diagram
-
-
-
-
(R)-2-Methylmalonyl-CoA
Succinyl-CoA
show the reaction diagram
-
-
-
-
(R)-2-Methylmalonyl-CoA
Succinyl-CoA
show the reaction diagram
-
-
-
?
(R)-2-Methylmalonyl-CoA
Succinyl-CoA
show the reaction diagram
-
-
-
?
(R)-2-Methylmalonyl-CoA
Succinyl-CoA
show the reaction diagram
-
-
-
?
(R)-2-Methylmalonyl-CoA
Succinyl-CoA
show the reaction diagram
-
-
-
?
(R)-2-Methylmalonyl-CoA
Succinyl-CoA
show the reaction diagram
-
-
-
?
(R)-2-Methylmalonyl-CoA
Succinyl-CoA
show the reaction diagram
-
-
-
-
?
(R)-2-Methylmalonyl-CoA
Succinyl-CoA
show the reaction diagram
-
-
-
r
(R)-2-Methylmalonyl-CoA
Succinyl-CoA
show the reaction diagram
-
-
-
r
(R)-2-Methylmalonyl-CoA
Succinyl-CoA
show the reaction diagram
-
-
-
-
r
(R)-2-Methylmalonyl-CoA
Succinyl-CoA
show the reaction diagram
-
-
-
-
(R)-2-Methylmalonyl-CoA
Succinyl-CoA
show the reaction diagram
-
-
-
-
(R)-2-Methylmalonyl-CoA
Succinyl-CoA
show the reaction diagram
-
-
-
?
(R)-2-Methylmalonyl-CoA
Succinyl-CoA
show the reaction diagram
Q6TMA2, Q84FZ1
-
-
?
(R)-2-Methylmalonyl-CoA
Succinyl-CoA
show the reaction diagram
-
-
-
-
?
(R)-2-Methylmalonyl-CoA
Succinyl-CoA
show the reaction diagram
-
-
-
?
(R)-2-Methylmalonyl-CoA
Succinyl-CoA
show the reaction diagram
-
-
-
-
?
(R)-2-Methylmalonyl-CoA
Succinyl-CoA
show the reaction diagram
-
-
-
?
(R)-2-Methylmalonyl-CoA
Succinyl-CoA
show the reaction diagram
Q8F222
-
-
?
(R)-2-Methylmalonyl-CoA
Succinyl-CoA
show the reaction diagram
-
-
-
?
(R)-2-Methylmalonyl-CoA
Succinyl-CoA
show the reaction diagram
P11652, P11653
-
-
?
(R)-2-Methylmalonyl-CoA
Succinyl-CoA
show the reaction diagram
Q8Y2U5
-
-
?
(R)-2-Methylmalonyl-CoA
Succinyl-CoA
show the reaction diagram
Q8MI68, -
-
-
-
?
(R)-2-Methylmalonyl-CoA
Succinyl-CoA
show the reaction diagram
-, P22033
-
-
-
?
(R)-2-Methylmalonyl-CoA
Succinyl-CoA
show the reaction diagram
-
r
-
-
(R)-2-Methylmalonyl-CoA
Succinyl-CoA
show the reaction diagram
-, Q6TMA2, Q84FZ1
MCM forms a complex with MeaB
-
?
(R)-2-Methylmalonyl-CoA
Succinyl-CoA
show the reaction diagram
-
MCM forms a complex with MeaB
-
?
(R)-2-Methylmalonyl-CoA
Succinyl-CoA
show the reaction diagram
-
Sbm is only known to accept or produce (R)-2-methylmalonyl-CoA
-
-
r
(R)-2-Methylmalonyl-CoA
Succinyl-CoA
show the reaction diagram
Streptomyces clavuligerus CKD1119
-
-
-
-
?
(S)-methylmalonyl-CoA
succinyl-CoA
show the reaction diagram
-
-
-
-
?
4-Carboxy-2-oxobutanoyl-CoA
?
show the reaction diagram
-
-
-
-
-
Ethylmalonyl-CoA
Methylsuccinyl-CoA
show the reaction diagram
-
reacts about 1000-10000 times moreslowly than the natural substrate
-
-
Ethylmalonyl-CoA
(2R)-Methylsuccinyl-CoA
show the reaction diagram
-
reacts about 1000-10000 times moreslowly than the natural substrate
+ a small amount of (2S)-diastereoisomer
-
Methylmalonyl-carba(dethia)-CoA
Succinyl-carby(dethia)-CoA
show the reaction diagram
-
r
-
-
methylmalonyl-CoA
succinyl-CoA
show the reaction diagram
-
-
-
-
-
methylmalonyl-CoA
succinyl-CoA
show the reaction diagram
-
-
-
-
r
Succinyl-carba(dethia)-CoA
?
show the reaction diagram
-
-
-
-
-
Succinyl-CoA
?
show the reaction diagram
-
succinyl-CoA is isomerized to methylmalonyl-CoA before incorporation into the macrocyclic lactone of erythromycin
-
-
-
Succinyl-CoA
?
show the reaction diagram
-
production of propionate from succinate
-
-
-
Succinyl-dicarba(dethia)-CoA
?
show the reaction diagram
-
-
-
-
-
methylmalonyl-CoA
succinyl-CoA
show the reaction diagram
-
-
-
-
r
additional information
?
-
-
this enzyme is deficient in methylmalonic acidemia
-
-
-
additional information
?
-
-
acts as a cobalamin binding protein
-
-
-
additional information
?
-
-
P-loop GTPase MeaB plays an auxiliary role in catalytic reaction. MeaB increases affinity of the mutase for cofactor 5-deoxyadenosylcobalamin twofold
-
-
-
additional information
?
-
-, P22033
human MMAA and MUT interact in vitro and in vivo. This interaction is nucleotide-selective for MMAA and apoenzyme-dependent for MUT and is associated with stimulation of MMAA GTPase activity by MUT
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
(R)-2-Methyl-3-oxopropanoyl-CoA
?
show the reaction diagram
-
-
-
-
-
(R)-2-Methyl-3-oxopropanoyl-CoA
?
show the reaction diagram
-
key position in metabolism of propionic acid
-
-
-
(R)-2-Methylmalonyl-CoA
Succinyl-CoA
show the reaction diagram
-
-
-
?
(R)-2-Methylmalonyl-CoA
Succinyl-CoA
show the reaction diagram
-
-
-
?
(R)-2-Methylmalonyl-CoA
Succinyl-CoA
show the reaction diagram
-
-
-
?
(R)-2-Methylmalonyl-CoA
Succinyl-CoA
show the reaction diagram
-
-
-
?
(R)-2-Methylmalonyl-CoA
Succinyl-CoA
show the reaction diagram
-
-
-
?
(R)-2-Methylmalonyl-CoA
Succinyl-CoA
show the reaction diagram
-
-
-
?
(R)-2-Methylmalonyl-CoA
Succinyl-CoA
show the reaction diagram
-
-
-
r
(R)-2-Methylmalonyl-CoA
Succinyl-CoA
show the reaction diagram
-
-
-
r
(R)-2-Methylmalonyl-CoA
Succinyl-CoA
show the reaction diagram
-
-
-
?
(R)-2-Methylmalonyl-CoA
Succinyl-CoA
show the reaction diagram
Q6TMA2, Q84FZ1
-
-
?
(R)-2-Methylmalonyl-CoA
Succinyl-CoA
show the reaction diagram
Q8F222
-
-
?
(R)-2-Methylmalonyl-CoA
Succinyl-CoA
show the reaction diagram
P11652, P11653
-
-
?
(R)-2-Methylmalonyl-CoA
Succinyl-CoA
show the reaction diagram
Q8Y2U5
-
-
?
(R)-2-Methylmalonyl-CoA
Succinyl-CoA
show the reaction diagram
-, Q6TMA2, Q84FZ1
MCM forms a complex with MeaB
-
?
Succinyl-CoA
?
show the reaction diagram
-
succinyl-CoA is isomerized to methylmalonyl-CoA before incorporation into the macrocyclic lactone of erythromycin
-
-
-
Succinyl-CoA
?
show the reaction diagram
-
production of propionate from succinate
-
-
-
(R)-2-Methylmalonyl-CoA
Succinyl-CoA
show the reaction diagram
-
MCM forms a complex with MeaB
-
?
additional information
?
-
-
this enzyme is deficient in methylmalonic acidemia
-
-
-
additional information
?
-
-
acts as a cobalamin binding protein
-
-
-
COFACTOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
5'-deoxyadenosylcobalamin
-
P-loop GTPase MeaB increases affinity of the mutase for cofactor twofold, in presence of MeaB and GDP, affinity decreases fivifold
5'-deoxyadenosylcobalamin
B7XBM0, -
the apoenzyme is converted to a holoenzyme by incubation for 4 h at 4C with 0.01 mM 5'-deoxyadenosylcobalamin, the purified enzyme contains one mole of prosthetic 5'-deoxyadenosylcobalamin per mole of subunit
adenosylcobalamin
-
-
adenosylcobalamin
Q6TMA2, Q84FZ1
-
adenosylcobalamin
Q8Y2U5
-
adenosylcobalamin
-
-
adenosylcobalamin
-
-
adenosylcobalamin
-
dependent on adenosylcobalamin as prosthetic group, under cobalamin-deficient conditions, (R)-2-methylmalonyl-CoA and its precursor, propionyl-CoA, increase as a result of a decrease in the catalytic activity of MCM due to deficiency of adenosylcobalamin
adenosylcobalamin
-
dependent on
adenosylcobalamin
-
dependent on
adenosylcobalamin
-
dependent on adenosylcobalamin which is delivered by adenosyltransferase
adenosylcobalamin
B7XBM0, -
the apparent Km value of the apoenzyme is 22.7 nM
adenosylcobalamin
-
-
adenosylcobalamin
-
-
adenosylcobalamin
-
MCM activity with adenosylcobalamin increases linearly during the first 3-4 min
adenosylcobalamin
-, P22033
-
adenosylcobalamin
-
-
Coalpha(alpha-Benzimidazolyl)-Cobeta-adenosyl-cobamide
-
can serve as coenzyme
Coalpha-(alpha-Purinyl)-Cobeta-adenosylcobamide
-
can serve as coenzyme
Coalpha-Hydroxo-Cobeta-adenosylcobinamide
-
can serve as coenzyme
Coalpha[alpha-(Aden-7-yl)]-Cobeta-adenosyl-cobamide
-
can serve as coenzyme
Cobalamin
-
dependent on, 2 mol of cobalamin bound per mol of enzyme, are covalently attached
Cobalamin
-, P22033
essential to the function of methylmalonyl-CoA mutase, cobalamin is conversed to adenosylcobalamin
cobamide
-
dependent on; stimulates
cobamide
-
dependent on
cobamide
-
enzyme-bound and free 5'-deoxyadenonosylcobalamin molecules are frequently exchanged during incubation, deuterium is transferred from the 5' position of 5'-deoxyadenonosylcobalamin to the solvent, deuterium scrambling between the two diastereotopic 5'-positions occurrs
cobamide
-
-
cobamide
-
adenosylcobalamin protects the apoenzyme from inactivation by NEM or iodoacetamide. Km: 0.000021 mM; one molecule of enzyme contains about 2 molecules of adenosylcobalamin
cobamide
-
one molecule of enzyme contains about 2 molecules of adenosylcobalamin
cobamide
-
Km: 0.00009 mM
cobamide
-
dependent on
cobamide
-
required, Km: 0.00005 mM
cobamide
-
dependent on; Km: 0.000354 mM
cobamide
-
dependent on
deoxyadenosylcobinamide GDP
-
-
-
hydroxycobalamin
-
required for Sbm activity
vitamin B12
-
required
METALS and IONS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
Cl-
-
stimulates
NH4+
-
stimulates at 3 mM
PO43-
-
required, maximal activity at 50 mM
Rb+
-
stimulates at 3 mM
SO42-
-
stimulates
INHIBITORS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
(R)-2-Methyl-3-oxopropanoyl-CoA
-
substrate inhibition
2-(N,N-diethylamino)-diazenolate-2-oxide
-
1 mM, about 50% inhibition of enzyme activity. Similar inhibitory effects of 2-(N,N-diethylamino)-diazenolate-2-oxide in the presence of 25 mM glutathione and dithiothreitol
-
5,5'-dithiobis(2-nitrobenzoic acid)
-
-
allylmalonyl-CoA
-
competitive with wild-type, O2-independent suicide inactivation with mutant Y243A via an internal electron transfer from cob(II)alamin to the inhibitor radical
Ca2+
-
at high concentrations
Cyclopropylcarbonyl-CoA carboxylate
-
reversible mixed-type inhibition
ethylmalonyl-CoA
-
competitive with wild-type, O2-dependent suicide inactivation with mutant Y243A
Hg2+
B7XBM0, -
MCM activity is inhibited completely by the addition of 3 mM Hg2+
isobutyryl-CoA
-
R207Q and Y89F/R207Q mutants show conversion of adenosylcobalamin to hydroxycobalamin, indicating inactivation of the enzyme
Li+
-
slight inhibition at 3 mM
Methylenecyclopropylacetyl-CoA
-
reversible mixed-type inhibition
methylmalonyl-CoA
-
reversible mixed-type inhibition
n-Butyryl-CoA
-
R207Q and Y89F/R207Q mutants show conversion of adenosylcobalamin to hydroxycobalamin, indicating inactivation of the enzyme. No changes in wild-type and Y89F-mutant
Na+
-
slight inhibition at 3 mM
oxygen
-
600 microM, significant inhibition of enzyme activity
p-chloromercuribenzoate
-
-
p-hydroxymercuribenzoate
-
-
Mg2+
-
at high concentrations
additional information
-
inhibited by intrinsic factor
-
additional information
B7XBM0, -
Na+, K+, Ca2+, Fe2+, Mg2+, and Co2+ (all at 3 mM) and 3 mM EDTA do not cause inhibition of the MCM activity
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
(Cobeta-5'-Deoxyadenosine-5'-yl)-(p-cresolyl)cobamide
-
can serve as coenzyme, Km: 0.000064
-
adenosylcobalamin
-
required
hydroxocobalamin
-
supplementation of hydroxocobalamin results in a marked increase in the holo-MCM activity in a dose-dependent manner, although the holo-MCM activity does not exceed 30% of the total-MCM activity even if hydroxocobalamin is supplemented at 10 mM
methylmalonic acidemia protein
-
after 60 min of reaction, when MCM is inactive, the addition of methylmalonic acidemia protein increases the enzymatic activity through GTP hydrolysis, indicating reactivation of MCM by exchange of the damaged cofactor. Methylmalonic acidemia protein acts as a chaperone of human MCM
-
KM VALUE [mM]
KM VALUE [mM] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.085
-
(R)-2-Methyl-3-oxopropanoyl-CoA
-
-
0.24
-
(R)-2-Methyl-3-oxopropanoyl-CoA
-
-
0.31
-
(R)-2-Methyl-3-oxopropanoyl-CoA
-
-
1.5
-
(R)-2-Methyl-3-oxopropanoyl-CoA
-
-
0.0279
-
(R)-2-methylmalonyl-CoA
B7XBM0, -
in 100 mM potassium phosphate buffer (pH 7.5), at 37C
0.086
-
(R)-2-methylmalonyl-CoA
-
37C
0.102
-
(R)-2-methylmalonyl-CoA
-
37C, mutant H610N
0.124
-
(R)-2-methylmalonyl-CoA
-
wild-type, pH 7.0, 37C
0.133
-
(R)-2-methylmalonyl-CoA
-
37C, wild-type
0.152
-
(R)-2-methylmalonyl-CoA
-
presence of P-loop GTPase MeaB and GDP, 37C
0.364
-
(R)-2-methylmalonyl-CoA
-
37C, mutant H610A
0.11
-
(R,S)-methylmalonyl-CoA
-
37C, pH 7, in presence of 3 mM NH4+
0.13
-
(R,S)-methylmalonyl-CoA
-
37C, pH 7, without NH4+
0.06
-
(R/S)-2-methyl-3-oxopropanoyl-CoA
-
-
0.2
-
(R/S)-2-methyl-3-oxopropanoyl-CoA
-
-
0.132
-
4-Carboxy-2-oxobutanoyl-CoA
-
-
0.00024
-
adenosylcobalamin
-
37C, wild-type
0.00045
-
adenosylcobalamin
-
37C, mutant H610A
0.00052
-
adenosylcobalamin
-
37C, mutant H610N
0.00064
-
adenosylcobalamin
-
37C, pH 7, in presence of 3 mM NH4+
0.0086
-
adenosylcobalamin
-
37C, pH 7, without NH4+
0.136
-
methylmalonyl-carba(dethia)-coenzyme A
-
-
0.136
-
methylmalonyl-carba(dethia)-coenzyme A
-
succinyl-carba(dethia)-CoA
0.133
-
methylmalonyl-CoA
-
wild type, 37C
0.025
-
succinyl-CoA
-
-
0.062
-
succinyl-CoA
-
-
0.083
-
succinyl-CoA
-
25C, mutant H244A
0.085
-
succinyl-CoA
-
25C, mutant H244Q
0.096
-
succinyl-CoA
-
25C, wild-type
0.3474
-
succinyl-CoA
B7XBM0, -
in 100 mM potassium phosphate buffer (pH 7.5), at 37C
2.2
-
Succinyl-dicarba(dethia)-CoA
-
-
0.357
-
methylmalonyl-CoA
-
mutant Y89F, 37C
additional information
-
additional information
-
KM not detectable, methylmalonyl-CoA, mutant Y89F/R207Q, 37C; KM over 4, methylmalonyl-CoA, mutant R207Q, 37C
-
additional information
-
additional information
-
Km value for mutant Y243A with substrate (R)-2-methylmalonyl-CoA is above 10 mM
-
TURNOVER NUMBER [1/s]
TURNOVER NUMBER MAXIMUM[1/s]
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.003
-
(R)-2-methylmalonyl-CoA
-
37C, mutant H610N
0.024
-
(R)-2-methylmalonyl-CoA
-
37C, mutant H610A
0.33
-
(R)-2-methylmalonyl-CoA
-
mutant Y243A, pH 7.0, 37C
18
-
(R)-2-methylmalonyl-CoA
-
30C, with 5'-deoxyadenosylcobinamide GDP as cofactor
73
-
(R)-2-methylmalonyl-CoA
-
30C, with 5'-adenosylcobalamin as cofactor
120
-
(R)-2-methylmalonyl-CoA
-
37C, wild-type
132
-
(R)-2-methylmalonyl-CoA
-
37C
158
-
(R)-2-methylmalonyl-CoA
-
wild-type, pH 7.0, 37C
237
-
(R)-2-methylmalonyl-CoA
-
presence of P-loop GTPase MeaB and GDP, 37C
255
-
(R)-2-methylmalonyl-CoA
-
presence of P-loop GTPase MeaB, 37C
150
-
(R/S)-2-methyl-3-oxopropanoyl-CoA
-
30C
283
-
(R/S)-2-methyl-3-oxopropanoyl-CoA
-
37C
0.038
-
succinyl-CoA
-
25C, mutant H244A
0.66
-
succinyl-CoA
-
25C, mutant H244Q
6.08
-
succinyl-CoA
-
25C, mutant H244Q
Ki VALUE [mM]
Ki VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.0109
-
allylmalonyl-CoA
-
mutant Y243A, pH 7.0, 37C
0.425
-
allylmalonyl-CoA
-
wild-type, pH 7.0, 37C
0.0153
-
ethylmalonyl-CoA
-
mutant Y243A, pH 7.0, 37C
0.467
-
ethylmalonyl-CoA
-
wild-type, pH 7.0, 37C
SPECIFIC ACTIVITY [µmol/min/mg]
SPECIFIC ACTIVITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
0.000052
-
-
baby hamster kidney cells grown in Dulbecco's modified Eagle's medium supplemented with 10% fetal bovine serum, lacking hydroxycobalamin, 37C, pH 7.4
0.0002
-
-
cell extracts preincubated with 5 microM adenosylcobalamin, 37C, pH 7.4
0.06
-
B7XBM0, -
crude homogenate, at 40C
1.33
-
-
-
1.4
-
Q6TMA2, Q84FZ1
-
10.85
-
-
after UNO Q-1 purification
14
-
-
-
21
-
B7XBM0, -
after 350fold purification, at 40C
67.4
-
-
-
pH OPTIMUM
pH MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
6.5
8
-
-
7
9
-
-
7
-
-
-
7
-
B7XBM0, -
-
pH RANGE
pH RANGE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
6.5
8
-
active over this pH-range
TEMPERATURE OPTIMUM
TEMPERATURE OPTIMUM MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
35
-
B7XBM0, -
-
SOURCE TISSUE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
SOURCE
-
methylmalonyl-CoA mutase and propionyl-CoA carboxylase enzymes are co-expressed in neurons and found in all regions of the central nervous system except in astrocytes and oligodendrocytes. The highest expression in the developing brain is in the periventricular zones of telencephalon, midbrain, and rhombencephalon. The highest expression levels of MCM in adult rat CNS are in neocortex and hippocampal formation, thalamic and hypothalamic nuclei, midbrain nuclei such as the red nucleus and substantia nigra, as well as pons, medulla and the Purkinje and granular layers of cerebellum
Manually annotated by BRENDA team
Q8MI68, -
mandibular lymph node
Manually annotated by BRENDA team
-
peripheral blood lymphocyte
Manually annotated by BRENDA team
Q8MI68, -
oropharyngeal tonsil
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
MOLECULAR WEIGHT
MOLECULAR WEIGHT MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
78000
-
-
gel filtration
79000
-
-
SDS-PAGE
122000
124000
-
gel filtration, calculation from sedimentation and diffusion data
144000
-
-
gel filtration
145000
-
-
gel filtration
149000
-
B7XBM0, -
gel filtration
150000
-
-
gel filtration
150000
-
-
gel filtration
160000
-
-
Sbm runs at 80000 Da monomer and 160000 Da dimer, non-denaturing PAGE
163000
165000
-
sedimentation equilibrium analysis, gel filtration
165000
-
-
determination from sedimentation data
165000
-
-
gel filtration
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
?
-
x * 63000, SDS-PAGE
?
Q6TMA2, Q84FZ1
x * 78000, SDS-PAGE and deduced from nucleotide sequence of gene mcmA, x * 64000, SDS-PAGE and deduced from nucleotide sequence of gene mcmB
?
-
x * 80000, SDS-PAGE
dimer
-
2 * 72000, SDS-PAGE of reduced enzyme
dimer
-
1 * 61000 + 1 * 66000, SDS-PAGE
dimer
-
2 * 77500, SDS-PAGE
dimer
-
1 * 67000 + 1 * 79000, SDS-PAGE
dimer
-
2 * 72000, SDS-PAGE in presence of 2-mercaptoethanol
dimer
-
1 * 69465, beta-subunit, + 1 * 80147, alpha-subunit, calculation from nucleotide sequence
dimer
-
2 * 80000, non-denaturing PAGE, Sbm runs at 80000 Da monomer and 160000 Da dimer
homodimer
-
alpha2, 2 * 80000, SDS-PAGE
homodimer
-
-
homodimer
B7XBM0, -
2 * 75000, SDS-PAGE; 2 * 78250, calculated from amino acid sequence
homodimer
-, P22033
x-ray crystallography
monomer
-
1 * 80000, SDS-PAGE, Sbm runs at 80000 Da monomer and 160000 Da dimer
additional information
-
P-loop GTPase MeaB functions in GTP-dependent assembly of holomethyl-malonyl-CoA mutase and subsequent protection of radical intermediates during catalysis
additional information
-
holomutase enzyme binds G-protein chaperone MeaB 15fold more tightly in presence of guanosine 5-(beta-gamma-imino)triphosphate than of GDP, the apomutase binds MeaB with similar affinity in presence of either nucleotide. a large structural rearrangement accompanies interaction between the proteins and buries between 4000 and 8600 A2 of surface area. The intrinsic low GTPase activity of MeaB is stimulated 100fold by binding to the mutase
Crystallization/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
enzyme in the apo, holo, and substrate-bound ternary forms, sitting drop vapor diffusion method, using 1.6 M Na/K-phosphate, 0.1 M HEPES pH 7.5 (apo form), or 30% (w/v) PEG3350, 0.1 M Bis-Tris pH 5.5, 0.3 M (NH4)2SO4 (holo form), or 20% (w/v) PEG3350, 0.1 M Bis-Tris pH 5.5, 0.1 M (NH4)2SO4 (ternary form)
-, P22033
crystal structure at 2 A resolution of methylmalonyl-CoA mutase in complex with coenzyme B12 and with the partial substrate desulfoCoA
-
determination of the structure of substrate-free methylmalonyl-CoA mutase is initiated to provide further insight into the mechanism of radical formation; vapour diffusion at 23C
-
of the enzymatically inactive inhibitor-protein complex with hydroxycob(III)alamin
-
vapour diffusion at 23C, in the presence of succinyl-CoA, 3-carboxylpropyl-CoA or (2R)-carboxylpropyl-CoA
-
TEMPERATURE STABILITY
TEMPERATURE STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
25
50
B7XBM0, -
the enzyme, when incubated at various temperatures for 10 min at pH 7.0, is stable up to 25C, and complete loss of activity is observed at 50C
50
-
-
15 min, stable below
55
-
-
t1/2: 3 min
GENERAL STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
repeated freezing and thawing results in a gradual loss of activity
-
STORAGE STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
-20C, 1.5 mg protein /ml in 50 mM potassium phosphate, pH 7.4, stable for at least 6 months
-
-10C, enzyme from strain 52 W is quite stable, the enzyme from strain St 33 is much less so
-
-10C, stable for at least 3 months
-
-10C, 50 mM Tris/HCl buffer, pH 8.0, 1 mM dithiothreitol, about 20-30% loss of activity after 2 days
-
Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
nickel affinity chromatography
-
ammonium sulfate precipitation, TSKgel phenyl-Toyopearl column chromatography, TSKgel QAE-Toyopearl column chromatography, Bio-Scale CHT2-1 column chromatography, UNO Q-1 column chromatography, and Superdex 200 gel filtration
B7XBM0, -
expressed in Saccharomyces cerevisiae
-
IMAC column chromatography
-
Ni-NTA column chromatography, Resource Q column chromatography, and Superdex 200 gel filtration
-, P22033
Ni-NTA agarose resin chromatography
-
to homogeneity
-
Cloned/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
expression in Escherichia coli
-
expressed in Escherichia coli BL21(DE3) cells
-
expressed in Escherichia coli BL21(DE3)R3-Rosetta cells
-, P22033
mutant enzymes G94V, Y231N, R369H, G623R, H678R and G717V from patients suffering from the mut-form of methylmalonic acidemia, expression in Escherichia coli
-
expression in Escherichia coli
Q6TMA2, Q84FZ1
expression in COS cells
-
overexpression in Escherichia coli
-
expressed in Escherichia coli BL21 (DE3) cells and COS-7 cells
-
ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
G623R
-
six missense mutations, producing the amino acid changes G94V, Y231N, R369H, G623R, H678R and G717V are detected in L-methylmalonyl-CoA mutase cDNA of patients suffering from the mut-form of methylmalonic acidemia resulting from defective adenosylcobalamin binding. The mutations increase the Km for adenosylcobalamin by 40fold to 900fold, while the values for maximal velocity varies from 0.2% to nearly 100% of that of the wild-type protein
G717V
-
six missense mutations, producing the amino acid changes G94V, Y231N, R369H, G623R, H678R and G717V are detected in L-methylmalonyl-CoA mutase cDNA of patients suffering from the mut-form of methylmalonic acidemia resulting from defective adenosylcobalamin binding. The mutations increase the Km for adenosylcobalamin by 40fold to 900fold, while the values for maximal velocity varies from 0.2% to nearly 100% of that of the wild-type protein
G94V
-
six missense mutations, producing the amino acid changes G94V, Y231N, R369H, G623R, H678R and G717V are detected in L-methylmalonyl-CoA mutase cDNA of patients suffering from the mut-form of methylmalonic acidemia resulting from defective adenosylcobalamin binding. The mutations increase the Km for adenosylcobalamin by 40fold to 900fold, while the values for maximal velocity varies from 0.2% to nearly 100% of that of the wild-type protein
H678R
-
six missense mutations, producing the amino acid changes G94V, Y231N, R369H, G623R, H678R and G717V are detected in L-methylmalonyl-CoA mutase cDNA of patients suffering from the mut-form of methylmalonic acidemia resulting from defective adenosylcobalamin binding. The mutations increase the Km for adenosylcobalamin by 40fold to 900fold, while the values for maximal velocity varies from 0.2% to nearly 100% of that of the wild-type protein
R369H
-
six missense mutations, producing the amino acid changes G94V, Y231N, R369H, G623R, H678R and G717V are detected in L-methylmalonyl-CoA mutase cDNA of patients suffering from the mut-form of methylmalonic acidemia resulting from defective adenosylcobalamin binding. The mutations increase the Km for adenosylcobalamin by 40fold to 900fold, while the values for maximal velocity varies from 0.2% to nearly 100% of that of the wild-type protein
Y231N
-
six missense mutations, producing the amino acid changes G94V, Y231N, R369H, G623R, H678R and G717V are detected in L-methylmalonyl-CoA mutase cDNA of patients suffering from the mut-form of methylmalonic acidemia resulting from defective adenosylcobalamin binding. The mutations increase the Km for adenosylcobalamin by 40fold to 900fold, while the values for maximal velocity varies from 0.2% to nearly 100% of that of the wild-type protein
H224Q
-
lower turnover than wild-type enzyme
H244A
-
lower turnover than wild-type enzyme
H610A
-
weakened affinity to the cofactor and much lower turnover than wild-type enzyme
H610N
-
weakened affinity to the cofactor and much lower turnover than wild-type enzyme
R207Q
-
active site residue, mutation lowering kcat 10000-fold and increasing KM for methylmalonyl-CoA over 30fold
R207Q/Y86F
-
double mutant designed to mimic active site of isobutyryl-CoA mutase
Y243A
-
40000fold decrease in catalytic efficiency, twofold decrease of cob(II)alamin concentration under steady state turnover conditions, no loss of stereochemical preference for substrate
Y89F
-
active site residue, mutation lowering kcat and increasing KM for methylmalonyl-CoA
additional information
-
enzyme depletion by RNA interference results in accumulation of methylmalonic acid. Enzyme deletion mutants display reduced propionate incorporation into macromolecules and produce increased amounts of methylmalonic acid in the culture medium. Lentiviral delivery of gene into fibroblasts derived from a patient with mut0 class methylmalonic acidemia can partially restore propionate flux
APPLICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
medicine
-
lentiviral delivery of enzyme gene into fibroblasts derived from a patient with mut0 class methylmalonic acidemia can partially restore propionate flux
analysis
-
method for separation of methylmalonyl-CoA and succinyl-CoA by capillary electrophoresis suitable for evaluation of total and holo-enzyme activity in biological matrices. Application of method for the differential diagnosis of methylmalonic acidemia, in relation to protein or coenzyme defects
medicine
-
method for separation of methylmalonyl-CoA and succinyl-CoA by capillary electrophoresis suitable for evaluation of total and holo-enzyme activity in biological matrices. Application of method for the differential diagnosis of methylmalonic acidemia, in relation to protein or coenzyme defects
analysis
-
method for separation of methylmalonyl-CoA and succinyl-CoA by capillary electrophoresis suitable for evaluation of total and holo-enzyme activity in biological matrices. Application of method for the differential diagnosis of methylmalonic acidemia, in relation to protein or coenzyme defects
medicine
-
method for separation of methylmalonyl-CoA and succinyl-CoA by capillary electrophoresis suitable for evaluation of total and holo-enzyme activity in biological matrices. Application of method for the differential diagnosis of methylmalonic acidemia, in relation to protein or coenzyme defects