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Information on EC 2.5.1.6 - methionine adenosyltransferase and Organism(s) Rattus norvegicus and UniProt Accession P13444

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Rattus norvegicus
UNIPROT: P13444 not found.
Word Map
  • 2.5.1.6
  • self-assembled
  • gold
  • alkanethiols
  • film
  • photoelectron
  • electrode
  • electrochemical
  • fabric
  • infrared
  • coverage
  • ellipsometry
  • voltammetry
  • tunnel
  • impedance
  • s-adenosylhomocysteine
  • interfacial
  • silicon
  • cystathionine
  • meristem
  • thiolate
  • optoelectronic
  • surface-enhanced
  • headgroups
  • tripolyphosphate
  • transistor
  • photovoltaic
  • indium
  • polycrystalline
  • wettabl
  • wettability
  • electroactive
  • wafer
  • azobenzene
  • transsulfuration
  • micropatterned
  • beta-synthase
  • nanoscale
  • single-component
  • lithography
  • well-ordered
  • thin-film
  • transmethylation
  • medicine
  • semiconductor
  • stamp
  • microbalance
  • ferrocene
  • electrochemistry
  • synthesis
  • silane
  • quartz
  • field-effect
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
The taxonomic range for the selected organisms is: Rattus norvegicus
Synonyms
sams, mat2a, mat1a, s-adenosylmethionine synthetase, adomet synthetase, sam synthetase, mat ii, matalpha2, s-adenosyl-l-methionine synthetase, mat2beta, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
adenosylmethionine synthetase
-
-
-
-
AdoMet synthetase
-
-
-
-
ATP-methionine adenosyltransferase
-
-
-
-
MAT I
MAT II
284790
isozyme
MAT III
methionine adenosyltransferase
methionine S-adenosyltransferase
-
-
-
-
methionine-activating enzyme
-
-
-
-
S-adenosyl-L-methionine synthetase
-
-
-
-
S-adenosylmethionine synthase
-
-
-
-
S-adenosylmethionine synthetase
-
-
-
-
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
ATP + L-methionine + H2O = phosphate + diphosphate + S-adenosyl-L-methionine
show the reaction diagram
mechanism, key role of K182 in the correct positioning of the substrates, and D135 in stabilizing the sulfonium group formed in the product
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
adenosyl group transfer
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
ATP:L-methionine S-adenosyltransferase
-
CAS REGISTRY NUMBER
COMMENTARY hide
9012-52-6
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
ATP + L-methionine + H2O
phosphate + diphosphate + S-adenosyl-L-methionine
show the reaction diagram
-
-
-
?
2'-deoxy-ATP + L-methionine + H2O
?
show the reaction diagram
-
-
-
-
?
3'-deoxy-ATP + L-methionine + H2O
?
show the reaction diagram
-
-
-
-
?
ATP + L-methionine + H2O
phosphate + diphosphate + S-adenosyl-L-methionine
show the reaction diagram
ATP + L-methionine + H2O
S-adenosyl-L-methionine + phosphate + diphosphate
show the reaction diagram
ATP + methionine + H2O
S-adenosyl-L-methionine + phosphate + diphosphate
show the reaction diagram
tripolyphosphate + H2O
diphosphate + phosphate
show the reaction diagram
-
-
-
-
-
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
ATP + L-methionine + H2O
phosphate + diphosphate + S-adenosyl-L-methionine
show the reaction diagram
-
-
-
-
?
ATP + L-methionine + H2O
S-adenosyl-L-methionine + phosphate + diphosphate
show the reaction diagram
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Mn2+
-
optimal concentration at 2 mM
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
L-methionine
30% reduction in total activity is detected at 5 mM L-methionine
(2S,4S)-amino-4,5-epoxypentanoic acid
-
3-morpholinosydnoniimide
-
loss of liver MAT activity in vivo
ATP
-
ATP and methionine act as a switch between two different MAT III isoforms
bacterial lipopolysaccharide
-
carbon tetrachloride
-
depletion of glutathione levels reduces MAT I/III activities in vivo
Cu2+
isozyme subunit MATalpha2 is inhibited by 0.25 mM Cu2+ in the presence or absence of dithiothreitol, strong reduction in MAT2B gene expression induced by Cu2+ (60%), copper effects can only be prevented by buthionine sulfoximine, whereas N-acetylcysteine and neocuproine are ineffective
Dimethylsulfoxide
diphosphate
glycerol
-
inhibits kidney isoenzyme gamma
hydrogen peroxide
L-buthionine-(S,R)-sulfoximine
L-methionine
nitric oxide
p-chloromercuribenzoate
-
alpha and beta isoenzymes completely inhibited, gamma isoenzyme slightly inhibited
phosphate
-
individually a weak inhibitor, in combination with diphosphate there is a synergistic inhibitory effect
S-adenosylmethionine
S-nitrosoglutathione
S-nitrosoglutathione monoethyl ester
-
inactivates
S-nitrosylated glutathione
-
rapid and dose-dependent loss of enzymatic activity of MAT I/III
SIN-1
-
rapid and dose-dependent loss of enzymatic activity of MAT I/III
tripolyphosphate
-
activation or inhibition, depending on isoenzyme, S-adenosylmethionine and tripolyphosphate concentration
additional information
-
MAT is inactivated after 6 h of incubation in hypoxia (3% O2) in rat hepatocytes, prevented by NG-monomethyl-L-arginine methyl ester. Hepatic MAT s a sensible target for free radicals in vivo
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
L-methionine
17% increase is observed at 60 mM L-methionine
ATP
-
tripolyphosphatase activity stimulated by preincubation with ATP and methionine
Dimethylsulfoxide
dithiothreitol
-
required for alpha and beta isoenzymes activity, not required for gamma enzyme
E2F1
-
present continually in the MAT2A promoter during liver regeneration
-
E2F3
-
present continually in the MAT2A promoter during liver regeneration
-
E2F4
-
present continually in the MAT2A promoter during liver regeneration
-
forskolin
-
induction of enzyme in organ cell culture
glycerol
-
activates rat liver isoenzymes alpha and beta
isoproterenol
-
induction of enzyme in organ cell culture
L-methionine
17% increase of activity is observed at 60 mM L-methionine
methionine
-
stimulation of activity demonstrated in vivo. Tripolyphosphatase activity stimulated by preincubation with ATP and methionine
norepinephrine
-
induction of enzyme in organ cell culture
S-adenosylmethionine
SH-reagents
-
liver enzyme: requirement, tumor enzyme: no requirement
-
Sp1
-
binding of Sp1 to the MAT2A promoter is essential for the transcriptional up-regulation of the gene
-
tripolyphosphates
-
activation or inhibition, depending on isoenzyme, S-adenosylmethionine and tripolyphosphate concentration
additional information
-
no effect with ADP and methionine or S-adenosylmethionine
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.002 - 3.25
ATP
0.017 - 0.215
L-methionine
0.0083 - 1.12
methionine
0.006 - 0.007
Mg2+
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.583
S-adenosylmethionine
-
S-adenosylmethionine synthesis
0.125
tripolyphosphate
-
tripolyphosphatase activity
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.287 - 0.748
Cu2+
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.039
-
MAT I
0.096
-
glutathione/glutathione disulfide-refolded MAT III
0.098
-
MAT III
0.1
-
glutathione/glutathione disulfide-refolded MAT I
0.11
-
dithiothreitol-refolded MAT III
0.28
-
low-MW isozyme
3
-
beta isoenzyme from liver
4.61
-
high-MW isozyme
7.5
-
alpha isoenzyme from liver
32.75
-
beta form from liver
39
-
gamma isoenzyme from liver
78.24
-
alpha form from liver
31500
mutant C61S, presence of glutathione
32700
mutant C35S, presence of glutathione
69070
mutant C61S, presence of dithiothreitol
94470
mutant C35S, presence of dithiothreitol
95800
wild-type, presence of glutathione
110000
wild-type, presence of dithiothreitol
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.5 - 9.5
-
glutathione/glutathione disulfide-refolded MAT I
7.7 - 8.8
-
MAT III, MAT I and dithiothreitol-refolded MAT III
8.5 - 10
-
glutathione/glutathione disulfide-refolded MAT III
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.5 - 9.5
-
about 70-80% of maximal activity at pH 7.5 and 9.5
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
adult quiescent hepatocyte
Manually annotated by BRENDA team
-
a single form of enzyme
Manually annotated by BRENDA team
-
at night, 2.5fold increase of activity of isoform MAT II
Manually annotated by BRENDA team
-
isoforms MAT2AandMAT2beta are induced in culture-activated primary hepatic stellate cells and hepatic stellate cells from 10-day bile duct ligated rat livers. Hepatic stellate cell activation leads to a decline in intracellular S-adenosylmethionine and methyhthioadenosine levels, a drop in the S-adenosylmethionine/S-adenosylhomocysteine ratio, and global DNA hypomethylation. The decrease in S-adenosylmethionen levels is associated with lower MATII activity during activation
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
-
isoform MAT I, presence of two partially overlapping areas at the C-terminal end of the protein involved both in cytoplasmic retention and nuclear localization
Manually annotated by BRENDA team
-
isoform MAT I, in extrahepatic tissues, the protein colocalizes with nuclear matrix markers. Presence of two partially overlapping areas at the C-terminal end of the protein involved both in cytoplasmic retention and nuclear localization. Neither nuclear localization nor matrix binding requires activity. Nuclear accumulation of the active enzyme only correlates with histone H3K27 trimethylation among the epigenetic modifications evaluated
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
physiological function
-
MAT2A silencing in primary heaptic stellate cells results in decreased collagen and alpha-smooth muscle actin expression and cell growth and increased apoptosis
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
Sequence
METK1_RAT
397
0
43698
Swiss-Prot
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
200000
isozyme MAT I, gel filtration
44300
2 * 44300, analysis of association/dissociation between dimer and tetramer by gel filtration and MALDI-TOF MS; 4 * 44300, analysis of association/dissociation between dimer and tetramer by gel filtration and MALDI-TOF MS
47000
48000
48500
-
4 * 48500, high-MW isoenzyme, SDS-PAGE
89130
-
glutathione/glutathione disulfide-refolded MAT III, gel filtration
92700
97000
100000
-
beta isoenzyme from liver, gel filtration
110000
120000
160000
-
beta isoenzyme from liver, gel filtration
190000
-
gamma isoenzyme from kidney, gel filtration
194900
200000
208000
210000
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
tetramer
isozyme MAT I
dimer
homodimer
-
isoform MAT III
homotetramer
-
isoform MAT I
monomer
-
in nuclear fractions, presence of active tetramers and monomers
tetramer
additional information
-
study of thermal unfolding, implications for structure and oligomerization pathway
CRYSTALLIZATION/commentary
ORGANISM
UNIPROT
LITERATURE
in complex with inhibitor (2S,4S)-amino-4,5-epoxypentanoic acid
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
C35S
reduction in Vmax value
C61S
reduction in Vmax value
F251D
-
inactive, but displays correct nuclear localization and matrix binding
additional information
-
MAT1A knockout mice, spontaneous steatohepatitis develops by 8 months, hepatocellular carcinoma develops by 18 months
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
47 - 51
-
Tm-value, irreversible thermal denaturation
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
significant decrease during the interval from 0-8 hr at 23ºC after decapitation. From here up to 72 hs post-mortem at 4ºC the activity remains at 60% of the initial value
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
0°C, 50 mM Tris/HCl, pH 7.8, 20% v/v glycerol, 0.2 mM DTT, 0.1 mM EDTA, 10 mM MgCl2, 0.1 M KCl, partially purified liver enzymes stable for at least 1 month
-
PURIFICATION/commentary
ORGANISM
UNIPROT
LITERATURE
2 forms: high-MW form and low-MW form
-
alpha isozyme from liver using immunoaffinity chromatography; beta isoenzyme from liver using several chromatographic steps
-
gamma isoenzyme from kidney
-
method that includes DEAE-Sephacel chromatography and phenyl Sepharose CL-4B chromatography
-
method that includes DEAE-Sepharose, phenyl-Sepharose and blue-Sepharose chromatographies and ultrafiltration
-
three isoforms: MAT-I, MAT-II and MAT-III, MAT-III to homogeneity
-
CLONED/commentary
ORGANISM
UNIPROT
LITERATURE
expressed in Escherichia coli BL21(DE3)
-
RENATURED/Commentary
ORGANISM
UNIPROT
LITERATURE
dithiothreitol-refolding in the presence or absence of 250 mM CuSO4
dithiothreitol-refolding in the presence or absence of 250 mM CuSO4
refolding by direct dialysis or by dilution after treatment with urea under several conditions
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
-
animals fed ethanol intragastrically for 9 weeks switch hepatic MAT expression from MAT1A to MAT2A followed by decrease in S-adenosylmethionine levels, hypomethylation of c-myc, increase in c-myc expression and increased DNA strand break accumulation; MAT1A knockout mice, spontaneous steatohepatitis develops by 8 months, hepatocellular carcinoma develops by 18 months
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Geller, A.M.; Kotb, M.Y.S.; Jernigan, H.M.; Kredich, N.M.
Purification and properties of rat lens methionine adenosyltransferase
Exp. Eye Res.
43
997-1008
1986
Rattus norvegicus
Manually annotated by BRENDA team
Tallan, H.H.; Cohen, P.A.
Methionine adenosyltransferase: kinetic properties of human and rat liver enzymes
Biochem. Med.
16
234-250
1976
Homo sapiens, Rattus norvegicus
Manually annotated by BRENDA team
Liau, M.C.; Lin, G.W.; Hurlbert, R.B.
Partial purification and characterization of tumor and liver S-adenosylmethionine synthetases
Cancer Res.
37
427-435
1977
Rattus norvegicus
Manually annotated by BRENDA team
Sullivan, D.M.; Hoffman, J.L.
Fractionation and kinetic properties of rat liver and kidney methionine adenosyltransferase isozymes
Biochemistry
22
1636-1641
1983
Rattus norvegicus
Manually annotated by BRENDA team
Hoffman, J.L.
Fractionation of methionine adenosyltransferase isozymes (rat liver)
Methods Enzymol.
94
223-228
1983
Rattus norvegicus
Manually annotated by BRENDA team
Cabrero, C.; Puerta, J.; Alemany, S.
Purification and comparison of two forms of S-adenosyl-L-methionine synthetase from rat liver
Eur. J. Biochem.
170
299-304
1987
Rattus norvegicus
Manually annotated by BRENDA team
Okada, G.; Teraoka, H.; Tsukada, K.
Multiple species of mammalian S-adenosylmethionine synthetase. Partial purification and characterization
Biochemistry
20
934-940
1981
Rattus norvegicus
Manually annotated by BRENDA team
Suman, Y.; Shimizu, K.; Tsukada, K.
Isozymes of S-adenosylmethionine synthetase from rat liver: isolation and characterization
J. Biochem.
100
67-75
1986
Rattus norvegicus
Manually annotated by BRENDA team
Mingorance, J.; Alvarez, L.; Pajares, M.A.; Mato, J.M.
Recombinant rat liver S-adenosyl-L-methionine synthetase tetramers and dimers are in equilibrium
Int. J. Biochem. Cell Biol.
29
485-491
1997
Rattus norvegicus
Manually annotated by BRENDA team
Avila, M.A.; Corrales, F.J.; Ruiz, F.; Sanchez-Gongora, E.; Mingorance, J.; Carretero, M.V.; Mato, J.M.
Specific interaction of methionine adenosyltransferase with free radicals
Biofactors
8
27-32
1998
Rattus norvegicus
Manually annotated by BRENDA team
del Pino, M.M.; Corrales, F.J.; Mato, J.M.
Hysteretic behavior of methionine adenosyltransferase III. Methionine switches between two conformations of the enzyme with different specific activity
J. Biol. Chem.
275
23476-23482
2000
Rattus norvegicus
Manually annotated by BRENDA team
Ekegren, T.; Aquilonius, S.M.; Gomes-Trolin, C.
A comparative study of methionine adenosyltransferase activity and regional distribution in mammalian spinal cord
Biochem. Pharmacol.
60
441-445
2000
Bos taurus, Felis catus, Macaca mulatta, Rattus norvegicus, Sus scrofa
Manually annotated by BRENDA team
Lopez-Vara, M.C.; Gasset, M.; Pajares, M.A.
Refolding and characterization of rat liver methionine adenosyltransferase from Escherichia coli inclusion bodies
Protein Expr. Purif.
19
219-226
2000
Rattus norvegicus
Manually annotated by BRENDA team
Corrales, F.J.; Perez-Mato, I.; Sanchez Del Pino, M.M.; Ruiz, F.; Castro, C.; Garcia-Trevijano, E.R.; Latasa, U.; Martinez-Chantar, M.L.; Martinez-Cruz, A.; Avila, M.A.; Mato, J.M.
Regulation of mammalian liver methionine adenosyltransferase
J. Nutr.
132
2377S-2381S
2002
Escherichia coli, Homo sapiens, Rattus norvegicus
Manually annotated by BRENDA team
Lu, S.C.; Mato, J.M.
Role of methionine adenosyltransferase and S-adenosylmethionine in alcohol-associated liver cancer
Alcohol
35
227-234
2005
Homo sapiens, Rattus norvegicus
Manually annotated by BRENDA team
Iloro, I.; Chehin, R.; Goni, F.M.; Pajares, M.A.; Arrondo, J.L.
Methionine adenosyltransferase alpha-helix structure unfolds at lower temperatures than beta-sheet: a 2D-IR study
Biophys. J.
86
3951-3958
2004
Rattus norvegicus
Manually annotated by BRENDA team
Sanchez-Perez, G.F.; Gasset, M.; Calvete, J.J.; Pajares, M.A.
Role of an intrasubunit disulfide in the association state of the cytosolic homo-oligomer methionine adenosyltransferase
J. Biol. Chem.
278
7285-7293
2003
Rattus norvegicus (P13444)
Manually annotated by BRENDA team
Kim, J.S.; Coon, S.L.; Blackshaw, S.; Cepko, C.L.; Moller, M.; Mukda, S.; Zhao, W.Q.; Charlton, C.G.; Klein, D.C.
Methionine adenosyltransferase:adrenergic-cAMP mechanism regulates a daily rhythm in pineal expression
J. Biol. Chem.
280
677-684
2005
Rattus norvegicus
Manually annotated by BRENDA team
Gonzalez, B.; Pajares, M.A.; Hermoso, J.A.; Guillerm, D.; Guillerm, G.; Sanz-Aparicio, J.
Crystal structures of methionine adenosyltransferase complexed with substrates and products reveal the methionine-ATP recognition and give insights into the catalytic mechanism
J. Mol. Biol.
331
407-416
2003
Rattus norvegicus (P13444)
Manually annotated by BRENDA team
Delgado, M.; Perez-Miguelsanz, J.; Garrido, F.; Rodriguez-Tarduchy, G.; Perez-Sala, D.; Pajares, M.A.
Early effects of copper accumulation on methionine metabolism
Cell. Mol. Life Sci.
65
2080-2090
2008
Rattus norvegicus (P13444), Rattus norvegicus (P18298), Rattus norvegicus
Manually annotated by BRENDA team
Rodriguez, J.L.; Boukaba, A.; Sandoval, J.; Georgieva, E.I.; Latasa, M.U.; Garcia-Trevijano, E.R.; Serviddio, G.; Nakamura, T.; Avila, M.A.; Sastre, J.; Torres, L.; Mato, J.M.; Lopez-Rodas, G.
Transcription of the MAT2A gene, coding for methionine adenosyltransferase, is up-regulated by E2F and Sp1 at a chromatin level during proliferation of liver cells
Int. J. Biochem. Cell Biol.
39
842-850
2007
Rattus norvegicus (P18298)
Manually annotated by BRENDA team
Reytor, E.; Perez-Miguelsanz, J.; Alvarez, L.; Perez-Sala, D.; Pajares, M.A.
Conformational signals in the C-terminal domain of methionine adenosyltransferase I/III determine its nucleocytoplasmic distribution
FASEB J.
23
3347-3360
2009
Rattus norvegicus
Manually annotated by BRENDA team
Ramani, K.; Yang, H.; Kuhlenkamp, J.; Tomasi, L.; Tsukamoto, H.; Mato, J.M.; Lu, S.C.
Changes in the expression of methionine adenosyltransferase genes and S-adenosylmethionine homeostasis during hepatic stellate cell activation
Hepatology
51
986-995
2010
Homo sapiens, Rattus norvegicus
Manually annotated by BRENDA team
Pajares, M.A.; Alvarez, L.; Perez-Sala, D.
How are mammalian methionine adenosyltransferases regulated in the liver? A focus on redox stress
FEBS Lett.
587
1711-1716
2013
Rattus norvegicus
Manually annotated by BRENDA team
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