Information on EC 2.1.1.13 - methionine synthase

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

EC NUMBER
COMMENTARY
2.1.1.13
-
RECOMMENDED NAME
GeneOntology No.
methionine synthase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
5-methyltetrahydrofolate + L-homocysteine = tetrahydrofolate + L-methionine
show the reaction diagram
mechanism
-
5-methyltetrahydrofolate + L-homocysteine = tetrahydrofolate + L-methionine
show the reaction diagram
mechanism
-
5-methyltetrahydrofolate + L-homocysteine = tetrahydrofolate + L-methionine
show the reaction diagram
review, detailed mechanism
-
5-methyltetrahydrofolate + L-homocysteine = tetrahydrofolate + L-methionine
show the reaction diagram
mechanism; ordered sequential mechanism
-
5-methyltetrahydrofolate + L-homocysteine = tetrahydrofolate + L-methionine
show the reaction diagram
remethylation of inactivated enzyme and interaction with flavodoxin
-
5-methyltetrahydrofolate + L-homocysteine = tetrahydrofolate + L-methionine
show the reaction diagram
enzyme exists in two different conformations that interconvert in the cob(II)alamin oxidation state, control of reactivity
-
5-methyltetrahydrofolate + L-homocysteine = tetrahydrofolate + L-methionine
show the reaction diagram
mechanism
-
5-methyltetrahydrofolate + L-homocysteine = tetrahydrofolate + L-methionine
show the reaction diagram
mechanism
-
5-methyltetrahydrofolate + L-homocysteine = tetrahydrofolate + L-methionine
show the reaction diagram
mechanism
Escherichia coli K12
-
-
5-methyltetrahydrofolate + L-homocysteine = tetrahydrofolate + L-methionine
show the reaction diagram
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
methyl group transfer
-
-
-
-
PATHWAY
KEGG Link
MetaCyc Link
Biosynthesis of secondary metabolites
-
Cysteine and methionine metabolism
-
folate transformations I
-
folate transformations II
-
formylTHF biosynthesis
-
Metabolic pathways
-
methionine biosynthesis I
-
methionine biosynthesis III
-
methionine salvage II (mammalia)
-
One carbon pool by folate
-
Selenocompound metabolism
-
SYSTEMATIC NAME
IUBMB Comments
5-methyltetrahydrofolate:L-homocysteine S-methyltransferase
Contains zinc and cobamide. The enzyme becomes inactivated occasionally during its cycle by oxidation of Co(I) to Co(II). Reactivation by reductive methylation is catalysed by the enzyme itself, with S-adenosyl-L-methionine as the methyl donor and a reducing system. For the mammalian enzyme, the reducing system involves NADPH and EC 1.16.1.8, [methionine synthase] reductase. In bacteria, the reducing agent is flavodoxin, and no further catalyst is needed (the flavodoxin is kept in the reduced state by NADPH and EC 1.18.1.2, ferredoxin---NADP+ reductase). Acts on the monoglutamate as well as the triglutamate folate, in contrast with EC 2.1.1.14, 5-methyltetrahydropteroyltriglutamate---homocysteine S-methyltransferase, which acts only on the triglutamate.
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
5-methyltetrahydrofolate homocysteine methyltransferase
-
-
5-methyltetrahydrofolate-homocysteine methyltransferase
-
-
5-methyltetrahydrofolate-homocysteine S-methyltransferase
-
-
-
-
5-methyltetrahydrofolate-homocysteine transmethylase
-
-
-
-
5-methyltetrahydrofolate-homocysteine transmethylase
-
-
B12 N5-methyltetrahydrofolate homocysteine methyltransferase
-
-
-
-
B12-dependent methionine synthase
-
-
cobalamin-dependent methionine synthase
-
-
cobalamin-dependent methionine synthase
-
-
folate-dependent methionine synthase
-
-
methionine synthase
-
-
-
-
methionine synthase
-
-
methionine synthase
-
-
methionine synthetase
-
-
-
-
methyltetrahydrofolate-homocysteine vitamin B12 methyltransferase
-
-
-
-
methyltransferase, methyltetrahydrofolate-homocysteine
-
-
-
-
MetS
-
-
N-methyltetrahydrofolate:L-homocysteine methyltransferase
-
-
-
-
N-methyltetrahydrofolate:L-homocysteine methyltransferase
-
-
N5-methyltetrahydrofolate methyltransferase
-
-
-
-
N5-methyltetrahydrofolate-homocysteine cobalamin methyltransferase
-
-
-
-
N5-methyltetrahydrofolic-homocysteine vitamin B12 transmethylase
-
-
-
-
tetrahydrofolate methyltransferase
-
-
-
-
tetrahydropteroylglutamate methyltransferase
-
-
-
-
tetrahydropteroylglutamic methyltransferase
-
-
-
-
vitamin B12 methyltransferase
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
9033-23-2
-
ORGANISM
COMMENTARY
LITERATURE
SEQUENCE CODE
SEQUENCE DB
SOURCE
African Green monkey, Cos-7, i.e. SV40-transformed kidney cells
-
-
Manually annotated by BRENDA team
Chromatium sp.
D
-
-
Manually annotated by BRENDA team
Chromatium sp. D
D
-
-
Manually annotated by BRENDA team
Escherichia coli K12
K12
-
-
Manually annotated by BRENDA team
HeLa cells, HepG2 cells and transformed kidney cells
-
-
Manually annotated by BRENDA team
L. cv. Harunanijo
-
-
Manually annotated by BRENDA team
yellowtail
-
-
Manually annotated by BRENDA team
Ochromonas malhamensis
-
-
-
Manually annotated by BRENDA team
HTC and Phi-1 tumour cells
-
-
Manually annotated by BRENDA team
7 to 8-d-old piglets, milk from lactating sows
-
-
Manually annotated by BRENDA team
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
5-methyl-5,6,7,8-tetrahydropteroylheptaglutamate + homocysteine
?
show the reaction diagram
-
-
-
-
?
5-methyl-5,6,7,8-tetrahydropteroylpentaglutamate + L-homocysteine
?
show the reaction diagram
-
-
-
-
?
5-methyl-5,6,7,8-tetrahydropteroylpentaglutamate + L-homocysteine
?
show the reaction diagram
-
-
-
-
?
5-methyltetrahydrofolate + 2-mercaptoethanol
S-methylmercaptoethanol + tetrahydrofolate
show the reaction diagram
-
-
-
?
5-methyltetrahydrofolate + L-homocysteine
tetrahydrofolate + L-methionine
show the reaction diagram
-
-
-
-
?
5-methyltetrahydrofolate + L-homocysteine
tetrahydrofolate + L-methionine
show the reaction diagram
-
methionine biosynthesis
-
-
-
5-methyltetrahydrofolate + L-homocysteine
tetrahydrofolate + L-methionine
show the reaction diagram
-
gene expression is induced by light, but more strongly induced under salt, drough and cold stresses and by treatment with ABA or H2O2
-
-
?
N5-methyltetrahydrofolate + L-homocysteine
tetrahydrofolate + L-methionine
show the reaction diagram
-
-
-
-
?
N5-methyltetrahydrofolate + L-homocysteine
tetrahydrofolate + L-methionine
show the reaction diagram
-
-
-
-
?
N5-methyltetrahydrofolate + L-homocysteine
tetrahydrofolate + L-methionine
show the reaction diagram
-
-
-
?
N5-methyltetrahydrofolate + L-homocysteine
tetrahydrofolate + L-methionine
show the reaction diagram
-
-
-
-
?
N5-methyltetrahydrofolate + L-homocysteine
tetrahydrofolate + L-methionine
show the reaction diagram
-
-
-
-
?
N5-methyltetrahydrofolate + L-homocysteine
tetrahydrofolate + L-methionine
show the reaction diagram
-
transcription is not regulated by Met, but is enhanced by homocysteine and repressed by choline and betaine. Synthesis of the enzyme is also regulated posttranscriptionally
-
-
?
N5-methyltetrahydrofolate + L-homocysteine
tetrahydrofolate + L-methionine
show the reaction diagram
Escherichia coli K12
-
-
-
-
?
N5-methyltetrahydropteroylheptaglutamate + L-homocysteine
tetrahydropteroylheptaglutamate + L-methionine
show the reaction diagram
-
-
-
-
?
N5-methyltetrahydropteroylmonoglutamate + L-homocysteine
tetrahydropteroylmonoglutamate + L-methionine
show the reaction diagram
-
-
-
-
?
N5-methyltetrahydropteroylmonoglutamate + L-homocysteine
tetrahydropteroylmonoglutamate + L-methionine
show the reaction diagram
-
-
-
-
?
N5-methyltetrahydropteroylmonoglutamate + L-homocysteine
tetrahydropteroylmonoglutamate + L-methionine
show the reaction diagram
-
-
-
-
?
N5-methyltetrahydropteroylmonoglutamate + L-homocysteine
tetrahydropteroylmonoglutamate + L-methionine
show the reaction diagram
-
-
-
-
?
N5-methyltetrahydropteroylmonoglutamate + L-homocysteine
tetrahydropteroylmonoglutamate + L-methionine
show the reaction diagram
-
-
-
-
?
N5-methyltetrahydropteroylmonoglutamate + L-homocysteine
tetrahydropteroylmonoglutamate + L-methionine
show the reaction diagram
-
-
-
?
N5-methyltetrahydropteroylmonoglutamate + L-homocysteine
tetrahydropteroylmonoglutamate + L-methionine
show the reaction diagram
-
-
-
-
?
N5-methyltetrahydropteroylmonoglutamate + L-homocysteine
tetrahydropteroylmonoglutamate + L-methionine
show the reaction diagram
-
-
-
-
?
N5-methyltetrahydropteroylmonoglutamate + L-homocysteine
tetrahydropteroylmonoglutamate + L-methionine
show the reaction diagram
-
-
-
-
?
N5-methyltetrahydropteroylmonoglutamate + L-homocysteine
tetrahydropteroylmonoglutamate + L-methionine
show the reaction diagram
-
-
-
-
?
N5-methyltetrahydropteroylmonoglutamate + L-homocysteine
tetrahydropteroylmonoglutamate + L-methionine
show the reaction diagram
Ochromonas malhamensis
-
-
-
-
?
N5-methyltetrahydropteroylmonoglutamate + L-homocysteine
tetrahydropteroylmonoglutamate + L-methionine
show the reaction diagram
-
-
-
-
?
N5-methyltetrahydropteroylmonoglutamate + L-homocysteine
tetrahydropteroylmonoglutamate + L-methionine
show the reaction diagram
-
-
-
-
?
N5-methyltetrahydropteroylpentaglutamate + L-homocysteine
tetrahydropteroylpentaglutamate + L-methionine
show the reaction diagram
-
-
-
-
?
N5-methyltetrahydropteroylpentaglutamate + L-homocysteine
tetrahydropteroylpentaglutamate + L-methionine
show the reaction diagram
-
-
-
-
?
N5-methyltetrahydropteroyltriglutamate + L-homocysteine
tetrahydropteroyltriglutamate + L-methionine
show the reaction diagram
-
-
-
-
?
N5-methyltetrahydropteroyltriglutamate + L-homocysteine
tetrahydropteroyltriglutamate + L-methionine
show the reaction diagram
-
-
-
-
?
N5-methyltetrahydropteroyltriglutamate + L-homocysteine
tetrahydropteroyltriglutamate + L-methionine
show the reaction diagram
-
-
-
-
?
N5-methyltetrahydropteroyltriglutamate + L-homocysteine
tetrahydropteroyltriglutamate + L-methionine
show the reaction diagram
-
-
-
-
?
N5-methyltetrahydropteroyltriglutamate + L-homocysteine
tetrahydropteroyltriglutamate + L-methionine
show the reaction diagram
-
-
-
?
N5-methyltetrahydropteroyltriglutamate + L-homocysteine
tetrahydropteroyltriglutamate + L-methionine
show the reaction diagram
-
-
-
-
?
N5-methyltetrahydropteroyltriglutamate + L-homocysteine
tetrahydropteroyltriglutamate + L-methionine
show the reaction diagram
-
-
-
-
?
N5-methyltetrahydropteroyltriglutamate + L-homocysteine
tetrahydropteroyltriglutamate + L-methionine
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + L-homocysteine
methionine + S-adenosyl-L-homocysteine
show the reaction diagram
-
-
-
?
S-adenosyl-L-methionine + L-selenohomocysteine
selenomethionine + S-adenosyl-L-homocysteine
show the reaction diagram
-
-
-
?
S-adenosyl-L-methionine + tetrahydrofolate
5-methyltetrahydrofolate + S-adenosyl-L-homocysteine
show the reaction diagram
-
-
-
?
5-methyltetrahydrofolate + L-homocysteine
tetrahydrofolate + L-methionine
show the reaction diagram
-
homocysteine increases methionine synthase mRNA level
-
-
?
additional information
?
-
-
binding of the folate substrate
-
-
-
additional information
?
-
-
S-adenosylhomocysteine replaces homocysteine as methyl acceptor to a limited extent
-
-
-
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
5-methyltetrahydrofolate + L-homocysteine
tetrahydrofolate + L-methionine
show the reaction diagram
-
methionine biosynthesis
-
-
-
5-methyltetrahydrofolate + L-homocysteine
tetrahydrofolate + L-methionine
show the reaction diagram
-
gene expression is induced by light, but more strongly induced under salt, drough and cold stresses and by treatment with ABA or H2O2
-
-
?
5-methyltetrahydrofolate + L-homocysteine
tetrahydrofolate + L-methionine
show the reaction diagram
-
homocysteine increases methionine synthase mRNA level
-
-
?
N5-methyltetrahydrofolate + L-homocysteine
tetrahydrofolate + L-methionine
show the reaction diagram
-
transcription is not regulated by Met, but is enhanced by homocysteine and repressed by choline and betaine. Synthesis of the enzyme is also regulated posttranscriptionally
-
-
?
COFACTOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
Cobalamin
-
cobalamin serves as an intermediary in methyl transfer reactions, and it cycles between the methylcob(III)alamin and cob(I)alamin forms
cobinamide
-
more active than cyanocobalamin with rat liver enzyme, but inhibitory with E. coli enzyme
S-adenosyl-L-methionine
-
bacterial enzyme requires reduced FAD and S-adenosyl-L-methionine
S-adenosyl-L-methionine
-
partially stimulates
S-adenosyl-L-methionine
-
required
S-adenosyl-L-methionine
-
required
S-adenosyl-L-methionine
-
required
S-adenosyl-L-methionine
-
required; role of S-adenosyl-L-methionine
S-adenosyl-L-methionine
-
required
S-adenosyl-L-methionine
Chromatium sp.
-
-
S-adenosyl-L-methionine
-
required
S-adenosyl-L-methionine
-
required
vitamin B12
-
enzyme contains a derivative of vitamin B12 as prosthetic group
vitamin B12
-
enzyme contains a derivative of vitamin B12 as prosthetic group
vitamin B12
-
enzyme contains a derivative of vitamin B12 as prosthetic group
vitamin B12
-
enzyme contains a derivative of vitamin B12 as prosthetic group
vitamin B12
Chromatium sp., Rhodospirillum rubrum
-
enzyme contains a derivative of vitamin B12 as prosthetic group
vitamin B12
-
1 mol per mol of protein, MW 186000; enzyme contains a derivative of vitamin B12 as prosthetic group
vitamin B12
-
enzyme contains a derivative of vitamin B12 as prosthetic group; mechanism of conversion of apo- to holomethionine synthase by various forms of cobalamin
vitamin B12
-
enzyme contains a derivative of vitamin B12 as prosthetic group; mechanism of conversion of apo- to holomethionine synthase by various forms of cobalamin; methylcobalamin tightly bound and required
vitamin B12
-
enzyme contains a derivative of vitamin B12 as prosthetic group
vitamin B12
-
enzyme contains a derivative of vitamin B12 as prosthetic group
vitamin B12
-
enzyme contains a derivative of vitamin B12 as prosthetic group
vitamin B12
-
enzyme contains a derivative of vitamin B12 as prosthetic group; i.e. cobalamin, 1 mol per mol of enzyme
vitamin B12
-
dependent
vitamin B12
-
dependent on
vitamin B12
-
dependent
vitamin B12
-
dependent
vitamin B12
-
required for activity
vitamin B12
-
dependent on
FAD
-
enzyme requires reduced FAD and S-adenosyl-L-methionine
additional information
-
enzyme requires another protein fraction, ATP, Mg2+, FAD and a NADH-generating system
-
additional information
-
absolute requirement for a reducing system
-
additional information
-
absolute requirement for a reducing system
-
additional information
-
absolute requirement for a reducing system
-
additional information
-
absolute requirement for a reducing system
-
additional information
-
absolute requirement for a reducing system
-
METALS and IONS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
Co2+
-
-
Cu
-
1:1 stoichiometry with Co
Mg2+
-
required
Mg2+
-
activates
Zn2+
-
0.9 equiv. of zinc per mole, removal results in inactive enzyme
Zn2+
-
characterization of zinc site
Zn2+
-
zinc is coordinated by Cys-207, Cys-272, and Cys-273
Mg2+
-
activates
additional information
-
no other metals except for Co
INHIBITORS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
1-methyl-5-amino-benzimidazole
-
IC50: more than 0.15 mM
1-methyl-5-nitro-7-methoxybenzimidazole
-
IC50: 0.15 mM
1-methyl-5-nitro-benzimidazole
-
IC50: more than 0.15 mM
1-methylbenzimidazole
-
IC50: more than 0.15 mM
2,1,3-benzothiadiazole
-
IC50: more than 0.15 mM
2-nitro-1H-benzimidazole
-
IC50: 0.12 mM
4-amino-2,1,3-benzothiadiazole
-
IC50: more than 0.15 mM
4-nitro-2,1,3-benzothiadiazole
-
IC50: 0.08 mM
5-amino-7-methoxy-N1-methylbenzimidazole
-
IC50: 0.095 mM
5-amino-7-methoxybenzimidazole
-
IC50: more than 0.15 mM
5-aminobenzimidazole
-
IC50: more than 0.15 mM
5-methoxybenzimidazole
-
IC50: more than 0.15 mM
5-nitro-7-methoxybenzimidazole
-
IC50: 0.1 mM
benzimidazole
-
IC50: more than 0.15 mM
ZL-031
-
i.e. diethyl N-[4-[(2-[2,4-diamino-5-(2,3-dibromopropane)-5,6,7,8-tetrahydropyrido(3,2-d)pyrimidin-6-yl]methyl)amino]3-bromo-benzoyl]L-glutamate
ZL-033
-
i.e. N-[4-[(2-[2,4-diamino-5-(2,3-dibromopropane)-5,6,7,8-tetrahydropyrido(3,2-d)pyrimidin-6-yl]methyl)amino]3-bromo-benzoyl]L-glutamic acid
ACTIVATING COMPOUND
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
aquacob(III)alamin
-
the addition of 0.05 mM aquacob(III)alamin to the crude extract results in an about 13fold increase in activity which is not greatly affected by the addition of cytochrome P450 reductase or reductase domain of neuronal nitric oxide synthase
cadaverine
-
up to 40% stimulation at 1 mm
cyanocobalamin
-
supports methyltransferase in extracts of animal tissues and Escherichia coli
K+
-
at 67 mM 1.4 fold activity
Li+
-
at 67 mM, 1.3fold activity
methionine synthase reductase
-
restores the activity of human methionine synthase through reductive methylation of methionine synthase-bound cob(II)alamin. Oxidized methionine synthase reductase does not reactivate methionine synthase, the presence of methionine synthase reductase along with AqCbl or MeCbl causes a dramatic increase in methionine synthase activity (7fold for AqCbl and 20fold for MeCbl) as compared to the cofactor alone
-
methylcob(III)alamin
-
the addition of 0.05 mM methylcob(III)alamin to the crude extract results in an about 6fold increase in activity which is not greatly affected by the addition of cytochrome P450 reductase or reductase domain of neuronal nitric oxide synthase
Na+
-
at 67 mM 1.5 fold activity
NADPH
-
reactivation of methionine synthase is dependent on NADPH concentration in a hyperbolic manner with maximum activity at about 0.2 mM
NH4+
-
at 67 mM 1.5 fold activity
putrescine
-
up to 50% stimulation at 1 mm
-
S-adenosyl-L-methionine
-
required
S-adenosylmethionine
-
at about 0.0001 mM
spermidine
-
up to 2.5 fold stimulation at 1 mm
spermine
-
up to 4 fold stimulation at 1 mm
TrisHCl
-
at 67 mM 1.2 fold activity
vitamin B12
-
2 to 14 fold stimulation after addition to media due to posttranscriptional regulation
KM VALUE [mM]
KM VALUE [mM] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.0223
-
5-Methyl-5,6,7,8-tetrahydropteroylheptaglutamate
-
-
0.013
-
5-methyl-5,6,7,8-tetrahydropteroylmonoglutamate
-
-
0.0731
-
5-methyl-5,6,7,8-tetrahydropteroylmonoglutamate
-
-
0.004
-
5-Methyl-5,6,7,8-tetrahydropteroylpentaglutamate
-
-
0.0277
-
5-Methyl-5,6,7,8-tetrahydropteroylpentaglutamate
-
-
0.0244
-
5-methyl-5,6,7,8-tetrahydropteroyltriglutamate
-
-
2.4
-
5-methyltetrahydropteroylglutamate
-
-
0.0026
-
L-homocysteine
-
-
0.006
-
L-homocysteine
-
in 50 mM phosphate buffer, pH 7.4, at 37C
0.016
-
L-homocysteine
-
-
0.029
-
L-homocysteine
-
in 50 mM potassium phosphate (pH 7.2), 50 mM Tris-HCl (pH 7.2), 0.1 mM MgSO4, and 10 mM dithiothreitol, at 37C
0.069
-
L-homocysteine
-
-
0.43
-
L-homocysteine
-
-
0.017
-
L-Selenohomocysteine
-
-
0.03
-
methyltetrahydrofolate
-
-
0.089
-
N5-methyltetrahydrofolate
-
-
0.025
-
N5-methyltetrahydropteroylmonoglutamate
-
in 50 mM phosphate buffer, pH 7.4, at 37C
0.165
-
N5-methyltetrahydropteroylmonoglutamate
-
in 50 mM potassium phosphate (pH 7.2), 50 mM Tris-HCl (pH 7.2), 0.1 mM MgSO4, and 10 mM dithiothreitol, at 37C
0.00065
-
S-adenosyl-L-methionine
-
-
0.0016
-
S-adenosyl-L-methionine
-
-
0.035
-
S-methyltetrahydrofolate
-
-
-
0.06
-
methyltetrahydrofolate
-
-
additional information
-
additional information
-
-
-
TURNOVER NUMBER [1/s]
TURNOVER NUMBER MAXIMUM[1/s]
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.0217
-
S-adenosyl-L-methionine
-
-
0.0367
-
S-adenosyl-L-methionine
-
-
8.33
13
5-methyltetrahydrofolate
-
-
additional information
-
additional information
-
-
-
Ki VALUE [mM]
Ki VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.026
-
2-nitro-1H-benzimidazole
-
in 50 mM phosphate buffer, pH 7.4, at 37C
0.017
-
4-nitro-2,1,3-benzothiadiazole
-
in 50 mM phosphate buffer, pH 7.4, at 37C
IC50 VALUE [mM]
IC50 VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.15
-
1-methyl-5-amino-benzimidazole
-
IC50: more than 0.15 mM
0.15
-
1-methyl-5-nitro-7-methoxybenzimidazole
-
IC50: 0.15 mM
0.15
-
1-methyl-5-nitro-benzimidazole
-
IC50: more than 0.15 mM
0.15
-
1-methylbenzimidazole
-
IC50: more than 0.15 mM
0.15
-
2,1,3-benzothiadiazole
-
IC50: more than 0.15 mM
0.12
-
2-nitro-1H-benzimidazole
-
IC50: 0.12 mM
0.15
-
4-amino-2,1,3-benzothiadiazole
-
IC50: more than 0.15 mM
0.08
-
4-nitro-2,1,3-benzothiadiazole
-
IC50: 0.08 mM
0.095
-
5-amino-7-methoxy-N1-methylbenzimidazole
-
IC50: 0.095 mM
0.15
-
5-amino-7-methoxybenzimidazole
-
IC50: more than 0.15 mM
0.15
-
5-aminobenzimidazole
-
IC50: more than 0.15 mM
0.15
-
5-methoxybenzimidazole
-
IC50: more than 0.15 mM
0.1
-
5-nitro-7-methoxybenzimidazole
-
IC50: 0.1 mM
0.15
-
benzimidazole
-
IC50: more than 0.15 mM
0.01
-
ZL-031
-
at 37C
0.0014
-
ZL-033
-
at 37C
SPECIFIC ACTIVITY [µmol/min/mg]
SPECIFIC ACTIVITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
0.00017
-
-
muscle
0.00043
-
-
intestine
0.0005
-
-
recombinant enzyme from crude extract, in 0.2 M potassium phosphate buffer (pH 7.2), at 37C
0.0023
-
-
pancreas
0.003
-
-
brain
0.0073
-
-
kidney
0.0327
-
-
liver
1.54
-
-
recombinant enzyme after 3669fold purification, in 0.2 M potassium phosphate buffer (pH 7.2), at 37C
1.94
-
-
after 279fold purification at 37C
2.53
-
-
crude cell extract at 37C
9.3
11.7
-
-
additional information
-
-
assay method
additional information
-
-
-
additional information
-
-
-
additional information
-
-
-
additional information
-
-
assay method
additional information
-
-
-
additional information
-
-
assay method
additional information
-
-
assay method
additional information
-
-
assay method
additional information
-
-
assay method
additional information
-
-
assay method
additional information
-
Chromatium sp., Rhodospirillum rubrum
-
-
additional information
-
-
assay method
additional information
-
-
assay using HPLC with fluorescence detection
pH OPTIMUM
pH MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
6.5
7.2
-
-
7
-
-
-
7
-
-
assay at
7.5
7.8
Chromatium sp.
-
-
pH RANGE
pH RANGE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
6
7.5
-
pH 6.0: about 75% of maximum activity, pH 7.5: about 35% of activity maximum
6.2
8.2
-
pH about 50% of maximum activity at pH 6.2 and 8.2
6.5
8.3
Chromatium sp.
-
pH 6.5: about 30% of maximum activity, pH 8.3: about 85% of maximum activity
TEMPERATURE OPTIMUM
TEMPERATURE OPTIMUM MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
45
-
-
-
TEMPERATURE RANGE
TEMPERATURE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
10
39
-
10C: about 10% of maximum activity, 39C: maximum activity
15
31
-
15C: about 10% of maximum activity, 31C: maximum activity
SOURCE TISSUE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
SOURCE
-
adenocyrcinoma cell line
Manually annotated by BRENDA team
-
a variety of mammalian cell lines in tissue culture
Manually annotated by BRENDA team
-
a variety of mammalian cell lines in tissue culture
Manually annotated by BRENDA team
additional information
-
distribution in tissues
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
18% of total activity
Manually annotated by BRENDA team
-
69% of total activity
Manually annotated by BRENDA team
-
10% of total activity
Manually annotated by BRENDA team
PDB
SCOP
CATH
ORGANISM
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Moorella thermoacetica (strain ATCC 39073)
Thermotoga maritima (strain ATCC 43589 / MSB8 / DSM 3109 / JCM 10099)
Thermotoga maritima (strain ATCC 43589 / MSB8 / DSM 3109 / JCM 10099)
Thermotoga maritima (strain ATCC 43589 / MSB8 / DSM 3109 / JCM 10099)
Thermotoga maritima (strain ATCC 43589 / MSB8 / DSM 3109 / JCM 10099)
Thermotoga maritima (strain ATCC 43589 / MSB8 / DSM 3109 / JCM 10099)
Thermotoga maritima (strain ATCC 43589 / MSB8 / DSM 3109 / JCM 10099)
Thermotoga maritima (strain ATCC 43589 / MSB8 / DSM 3109 / JCM 10099)
Thermotoga maritima (strain ATCC 43589 / MSB8 / DSM 3109 / JCM 10099)
Thermotoga maritima (strain ATCC 43589 / MSB8 / DSM 3109 / JCM 10099)
MOLECULAR WEIGHT
MOLECULAR WEIGHT MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
36200
-
-
sedimentation in high salt buffer
40000
-
-
gel filtration
86000
-
-
SDS-PAGE
112000
-
-
GST fusion protein, SDS-PAGE
140000
150000
-
gel filtration, sedimentation coefficient in sucrose density gradients
140000
-
-
sucrose density gradient centrifugation
150000
-
-
gel filtration
151000
155000
-
gel filtration
153000
-
-
gel filtration
160000
-
-
gel filtration
186000
-
-
gel filtration
200000
-
-
gel filtration
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
?
-
x * 90000 + x * 45000 + x * 35000, SDS-PAGE of reduced enzyme
?
-
x * 49500, 2 different types of subunits, SDS-PAGE
?
-
x * 140000, SDS-PAGE, recombinant enzyme
dimer
-
2 * 40000, SDS-PAGE
monomer
-
x * 133000, SDS-PAGE
monomer
-
1 * 151000, SDS-PAGE
monomer
-
1 * 43100, light scattering
Crystallization/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
3.0 A structure of a 65000 Da C-terminal fragment of methionine synthase that spans the cobalamin- and the S-adenosylmethionine-binding domains, arranged in a conformation suitable for the methyl transfer from S-adenosylmethionine to cobalamin that occurs during activation
-
cobalamin-binding domain
-
hanging drop vapor diffusion method using 0.2 M potassium nitrate, 18% (w/v) PEG3350, or microbatch vapor diffusion method using 0.2 M potassium nitrate, 20% (w/v) PEG3350, 50 mM HEPES pH 7.5
-
the 65-kDa I690C/G743C MetH fragment is crystallized by the microbatch method, using 0.2 M potassium nitrate and 20% (w/v) PEG3350
-
sitting drop vapour diffusion method in reservoir solution of 0.1 M Tris/HCl pH 7.5 containing 0.1-0.4 M sodium acetate, 10-12% poly(ethylene glycol) 8000 and 10-12% poly(ethyleneglycol) 1000
-
hanging drop vapor diffusion method, using 25% 1,2-propanediol, 10% (v/v) glycerol, 5% (w/v) PEG 3000, 100 mM potassium citrate, pH 4.8, 15% (v/v) 1,2,3-heptanetriol, and 100 mM YCl3 (final pH, 5.2), at 4C
-
sitting drop vapour diffusion method, crystal structures of the N-terminal substrate-binding module of the enzyme and their complexes with the substrates L-homocysteine and 5-methyltetrahydrofolate
-
pH STABILITY
pH STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
5
-
-
unstable
5
-
-
precipitation at pH 5 inactivates
7
-
-
stability optimum, 0C, t1/2: 6 days
TEMPERATURE STABILITY
TEMPERATURE STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
37
-
-
2 h, complete loss of activity
37
-
-
the apoenzyme preincubated in the absence of methyl synthase reductase almost completely loses the ability to form holoenzyme after the subsequent addition of methylcobalamin and incubation at 37C for 10 min
GENERAL STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
rapid loss of activity in frozen state
-
apoenzyme is very unstable, may be stabilized by forming a complex with methylcobalamin
-
acetone inactivates
-
freezing and thawing, 40% loss of activity
-
homocysteine, 0.01 M, stabilizes
-
mercaptoethanol, 0.2 M, inactivation after 2 h at 24C or during freezing and thawing, no effect at 0C
-
precipitation at pH 5 inactivates
-
STORAGE STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
-20C, 15-20 mg/ml protein, stable for at least 1 month
-
-80C, methylated enzyme
-
4C, 20% loss of activity after 2 weeks
-
0C, pH 7, half-life 6 days
-
freeze-dried, 20% loss of activity after 3 months
-
-20C, ammonium sulfate paste containing homocysteine
-
0C, glutathione, N2-atmosphere, stable for at least a week
-
Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
glutathione agarose column chromatography
-
partial
Chromatium sp.
-
affinity chromatography
-
Hi-Trap column chromatography and MonoQ column chromatography
-
Ni-charged HiTrap chelating column chromatography and Mono Q column chromatography
-
nickel affinity chromatography using a Hi-Trap and a MonoQ column
-
preparation of different cobalamin forms
-
cobalamin affinity chromatography
-
Ni-NTA resin HisTrap column chromatography, HiPrep Q Sepharose column chromatography, and Resource Q column chromatography
-
Q-Sepharose column chromatography and cobalamin affinity chromatography
-
DEAE cellulose batch chromatography and Q-sepharose column chromatography
-
Cloned/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
expressed as a GST fusion protein in Saccharomyces cerevisiae strain SDYalpha
-
expressed in Escherichia coli Hms174(DE3) cells
-
mutant enzymes I690C/G743C and I690C/G743C/Y1139 are expressed in Escherichia coli Hms174(DE3) cells
-
expressed in Escherichia coli BL21(DE3) cells
-
expressed in Pichia pastoris cells
-
expressed in Sf9 insect cells
-
EXPRESSION
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
Glycine N-methyltransferase disruption significantly reduces hepatic expression
-
high expression in tumor cells
-
maximum mRNA accumulations of methionine synthase MS1 is attained in the evening
-
ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
D504A
-
the mutant exhibits 4% of wild type activity
D504N
-
the mutant exhibits 11% of wild type activity
D504S
-
the mutant exhibits 7% of wild type activity
D614A
-
the mutant exhibits less than 2% of wild type activity
D614N
-
the mutant exhibits less than 2% of wild type activity
D614S
-
the mutant exhibits 11% of wild type activity
E620Q
-
the mutation has no effect on enzyme activity
E620S
-
the mutation has no effect on enzyme activity
H128N
-
the mutant is 5fold less active compared to the wild type GST fusion protein
R530A
-
the mutant exhibits 33% of wild type activity
S448A
-
the mutant exhibits 67% of wild type activity
W576F
-
the mutant is 3fold less active compared to the wild type GST fusion protein
W576Y
-
the mutant is 8fold less active compared to the wild type GST fusion protein
Y527F
-
the mutant exhibits 67% of wild type activity
Cys310Ser
-
contains less than 0.05 equiv. of zinc, no proton release upon incubation with L-homocysteine, no enzymativc activity of holoenzyme
Cys311Ser
-
contains less than 0.05 equiv. of zinc, no proton release upon incubation with L-homocysteine, no enzymativc activity of holoenzyme
I690C/G743C
-
the variant of a C-terminal fragment of MetH locks the enzyme into the activation conformation without perturbing any of the residues in the vicinity of the active site
I690C/G743C
-
the mutant is locked in the reactivation conformation and found in both His-on and -off states
Y1139F
-
the mutation lowers the cobalamine reduction potential from -490 mV to -540 mV
D963E /K1071N
-
reduced activity
I690C/G743C/Y1139F
-
the I690C/G743C MetH variant is trapped in the activation conformation
additional information
-
truncated MetH(2-649) protein, contains 0.9 equiv. of zinc, still proton release upon incubation with L-homocysteine
additional information
-
truncated MetH(2-649) protein catalyzes partial enzymic reactions, truncated MetH(2-649) + Cys310Ala or + Cys311Ala indicate modular structure of enzyme comprising of four separate regions
Renatured/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
incubation of resolved apoenzyme with methyl-B12 results in spontaneous formation of holoenzyme
-
APPLICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
analysis
-
assay using HPLC with fluorescence detection
medicine
-
the A2756G polymorphism is not a risk factor for deep vein thrombosis among South Indians
analysis
-
assay using HPLC with fluorescence detection
medicine
-
B12-deficient diet leads to extremely low activity of enzyme possibly due to effects of coenzyme stabilization
medicine
-
comparison of enzyme in methionine dependent HTC cells and methionine independent Phi-1 cells
analysis
-
assay using HPLC with fluorescence detection