Information on EC 2.1.1.137 - arsenite methyltransferase

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

EC NUMBER
COMMENTARY hide
2.1.1.137
-
RECOMMENDED NAME
GeneOntology No.
arsenite methyltransferase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
S-adenosyl-L-methionine + arsenite = S-adenosyl-L-homocysteine + methylarsonate
show the reaction diagram
S-adenosyl-L-methionine + methylarsonite = S-adenosyl-L-homocysteine + dimethylarsinate
show the reaction diagram
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
transfer of methyl group
-
-
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
arsenate detoxification I (glutaredoxin)
-
-
SYSTEMATIC NAME
IUBMB Comments
S-adenosyl-L-methionine:arsenite As-methyltransferase
An enzyme of the biotransformation pathway that forms dimethylarsinate from inorganic arsenite and arsenate. It methylates arsenite to form methylarsonate, Me-AsO3H2, which is reduced by EC 1.20.4.2, methylarsonate reductase, to methylarsonite, Me-As(OH)2. Methylarsonite is also a substrate for this enzyme (EC 2.1.1.137), which converts it into the much less toxic compound dimethylarsinate (cacodylate), Me2As(O)-OH.
CAS REGISTRY NUMBER
COMMENTARY hide
167140-41-2
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ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
; gene arsM
-
-
Manually annotated by BRENDA team
-
UniProt
Manually annotated by BRENDA team
male golden syrian hamster
-
-
Manually annotated by BRENDA team
Cyanidioschyzon sp.
line ZF-1
-
-
Manually annotated by BRENDA team
; gene arsM
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
no activity in Aotus sp.
-
-
-
Manually annotated by BRENDA team
no activity in Caenorhabditis elegans
-
-
-
Manually annotated by BRENDA team
no activity in Callithrix jacchus
no activity in Cavia porcellus
guinea pig
-
-
Manually annotated by BRENDA team
no activity in Cheirogaleus medius
-
-
-
Manually annotated by BRENDA team
no activity in Daubentonia madagascariensis
-
-
-
Manually annotated by BRENDA team
no activity in Drosophila melanogaster
-
-
-
Manually annotated by BRENDA team
no activity in Galago senegalensis
-
-
-
Manually annotated by BRENDA team
no activity in Gorilla gorilla
-
-
-
Manually annotated by BRENDA team
no activity in Lemur catta
-
-
-
Manually annotated by BRENDA team
no activity in Nycticebus coucang
-
-
-
Manually annotated by BRENDA team
no activity in Pan troglodytes
-
-
-
Manually annotated by BRENDA team
no activity in Papio cynocephalus
-
-
-
Manually annotated by BRENDA team
no activity in Pongo pygmaeus
-
-
-
Manually annotated by BRENDA team
no activity in Propithecus verreauxi
-
-
-
Manually annotated by BRENDA team
no activity in Saguinus oedipus
; gene arsM
-
-
Manually annotated by BRENDA team
; gene arsM
-
-
Manually annotated by BRENDA team
strain CGA009
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
gene arsM
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
metabolism
-
key enzyme in the pathway for methylation of arsenicals
physiological function
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
S-adenosyl-L-methionine + arsenite
S-adenosyl-L-homocysteine + methylarsenite + dimethylarsenite + trimethylarsine
show the reaction diagram
S-adenosyl-L-methionine + arsenite
S-adenosyl-L-homocysteine + methylarsonate
show the reaction diagram
S-adenosyl-L-methionine + arsenite
S-adenosyl-L-homocysteine + methylarsonate + dimethylarsinous acid + dimethylarsinic acid
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + arsenite
S-adenosyl-L-homocysteine + monomethylarsenate + dimethylarsenate
show the reaction diagram
-
maximal conversion of arsenite to monomethylarsenate occurs at about 0.1 mM arsenite. Higher substrate concentrations inhibit monomethylarsenate yields. The production of dimethylarsenate increases as arsenite concentration increases from 0.0005 to 0.0083 mM, and then quickly decreases to zero
-
-
?
S-adenosyl-L-methionine + arsenite
S-adenosyl-L-homocysteine + monomethylarsonate + dimethylarsinic acid
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + arsenite
S-adenosyl-L-homocysteine + monomethylarsonous acid + monomethylarsonic acid + dimethylarsinic acid
show the reaction diagram
-
the enzyme methylates arsenite to dimethylarsinic acid as an end product and produces monomethylarsonous acid and monomethylarsonic acid as intermediates
-
-
?
S-adenosyl-L-methionine + methylarsonate
S-adenosyl-L-homocysteine + dimethylarsinous acid + dimethylarsinic acid
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + methylarsonite
S-adenosyl-L-homocysteine + dimethylarsinate
show the reaction diagram
additional information
?
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
S-adenosyl-L-methionine + arsenite
S-adenosyl-L-homocysteine + methylarsonate
show the reaction diagram
S-adenosyl-L-methionine + methylarsonite
S-adenosyl-L-homocysteine + dimethylarsinate
show the reaction diagram
additional information
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
S-adenosyl-L-methionine
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
arsenite
-
the enzyme activity is completely inhibited by elevated concentrations of the substrate arsenite (0.2 mM)
dimethylselenoxide
glutathione
-
addition of 20 mM GSH sharply inhibits methylation
methylselenic acid
selenate
-
more than 1 mM selenate necessary for 50% inhibition
Selenite
Sodium selenite
trimethyl-selenonium iodide
-
weak activator of recombinant As(III)-methyltransferase, weak inhibitor of arsenite methylation in hepatocytes
trimethylselenonium iodide
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weak activator of recombinant As(III)-methyltransferase, weak inhibitor of arsenite methylation in hepatocytes
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
dimethylselenoxide
dithiothreitol
glutathione
L-cysteine
thioredoxin
trimethyl-selenonium iodide
-
weak activator of recombinant As(III)-methyltransferase, weak inhibitor of arsenite methylation in hepatocytes
trimethylselenonium iodide
-
weak activator of recombinant As(III)-methyltransferase, weak inhibitor of arsenite methylation in hepatocytes
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0012 - 0.0185
arsenite
0.0007 - 0.003
methylarsonate
0.0031 - 0.0512
S-adenosyl-L-methionine
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0194
methylselenic acid
-
-
0.0014
Sodium selenite
-
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.0000000012
-
-
0.0000000016
-
-
0.00000000367
-
lung
0.0000000037
-
-
0.00000000667
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liver
0.0000000117
-
kidney
0.0000000241
-
testis
0.0000000283
-
-
0.00000128
-
-
0.00000167
-
-
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6.8
-
optimum if enzyme activity is measured in crude extracts
7 - 7.4
assay at
7.6
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-
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7 - 10
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-
7.5 - 11
-
pH 7.5: about 40% of maximal activity, pH 11: about 35% of maximal activity
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
60 - 70
Cyanidioschyzon sp.
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-
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
16 - 37
-
purified enzyme converts almost all arsenite to dimethylarsinate at temperatures of 1637C in pH 7.5 buffer, while at higher temperatures the rate of arsenite transformation is reduced
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
-
Manually annotated by BRENDA team
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-
Manually annotated by BRENDA team
-
prominent expression in intestine
Manually annotated by BRENDA team
-
-
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
29060
x * 29060, calculated from amino acid sequence
30000
-
x * 30000, His-tagged enzyme, SDS-PAGE
31100
-
x * 31100, truncated exon-4 and -5 skipping (DELTA4,5) mutant form, calculated from amino acid sequence
35400
-
x * 35400, His-tagged enzyme, calculated from amino acid sequence
38000
x * 38000, calculated from amino acid sequence
42000
x * 42000, SDS-PAGE
44980
Cyanidioschyzon sp.
x * 44980, calculated from amino acid sequence
46000
-
gel filtration
60000
-
gel filtration
80000
-
x * 80000, SDS-PAGE
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
peptide mapping
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
hanging drop vapor diffusion method, using 20% (w/v) polyethylene glycol 3000, 0.1 M Tris-HCl, pH 7.0, containing 0.2 M calcium acetate
Cyanidioschyzon sp.
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
45
-
the wild type enzyme exhibits about 40% residual activity after 120 min at 45C
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
DEAE anion exchange chromatography, Sephadex G-200, High Q anion exchange chromatographie, 40fold purification
-
DEAE cellulose, ammonium sulfate precipitation, Sephadex G-200, Sephadex G-100, 2000fold purification
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DEAE-cellulose, Sephadex G-200, Sephadex G-100, anion exchange chromatographie
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HisTrap column chromatography
-
native enzyme several thousandfold using pH-dependent fractionation, chromatofocusing, and S-adenosylhomocysteine-affinity chromatography, the purification of AS3MT from liver cytosol is dependent on the presence of 1 mM dithiothreitol and 5 mM GSH
Ni Sepharose column chromatography, gel filtration
-
Ni-NTA agarose column chromatography
-
Ni-NTA column chromatography
nickel affinity His GraviTrap column chromatography
-
recombinant enzyme
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
after expression in COS-1 cells and correction for transfection efficiency, the Trp173 allozyme displays 31%, Thr287 350%, Ile306 4.8%, and Thr287/Ile306 6.2% of the activity of the wild type allozyme, with 20, 190, 4.4, and 7.9% of the level of wild-type immunoreactive protein, respectively
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creation of a clonal human UROtsa cell line (UROtsa/F35) that expresses rat AS3MT and, unlike the parent UROtsa cell line, methylates inorganic arsenite and methylarsenite
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DNA and amino acid sequence determination and analysis
DNA and amino acid sequence determination and analysis, genotyping with method development and optimization, overview
-
expressed in an arsenic-sensitive strain of Escherichia coli
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expressed in Escherichia coli BL21 (DE3) pLysS cells
-
expressed in Escherichia coli BL21 cells
-
expressed in Escherichia coli BL21(DE3) cells
expressed in Escherichia coli BL21(DE3) pLysS cells
-
expressed in Escherichia coli BL21(DE3)pLysS cells
-
expressed in Escherichia coli DH10B cells
-
expressed in Escherichia coli DH5alpha and AW3110 cells
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expressed in the arsenite-sensitive Escherichia coli strain AW3110(DE3)
expression of rat AS3MT in a simian virus 40 (SV40)-transformed human urothelial cell line confers the capacity to methylate inorganic arsenic on cells that otherwise do not express AS3MT and that have a null phenotype for iAs methylation; gene arsM, DNA and amino acid sequence determination and analysis, sequence comparisons, phylogenetic analysis, genotype-phenotype correlations for arsenic methylation and AS3MT
gene arsM, DNA and amino acid sequence determination and analysis, sequence comparisons, phylogenetic analysis, genotype-phenotype correlations for arsenic methylation and AS3MT
gene arsM, DNA and amino acid sequence determination and analysis, sequence comparisons, phylogenetic analysis, genotype-phenotype correlations for arsenic methylation and AS3MT, recombinant expression
genes arsM and arsMC2, functional expression in enzyme-deficient Escherichia coli strain AW3110
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genotyping
-
wild-type ArsM and the C281/282S ArsMC2 variant, both with a His6 tag, are expressed in Escherichia coli
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
the enzyme is expressed in the absence of As(3+), and the expression is further enhanced after 6 h by 0.04 mM As(3+) exposure
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
C174A
Cyanidioschyzon sp.
-
the mutation leads to loss of As(III) methylation
C224A
Cyanidioschyzon sp.
-
the mutation leads to loss of As(III) methylation
C72A
Cyanidioschyzon sp.
-
the mutation leads to loss of As(III) methylation, but still shows trivalent methylarsenate methylation
Y70W
Cyanidioschyzon sp.
-
the mutant exhibits metalloid binding
C174A
-
the mutation leads to loss of As(III) methylation
-
C224A
-
the mutation leads to loss of As(III) methylation
-
C72A
-
the mutation leads to loss of As(III) methylation, but still shows trivalent methylarsenate methylation
-
Y70W
-
the mutant exhibits metalloid binding
-
C165S
-
inactive
C210S
-
inactive
C250S
-
the mutation favors S-adenosyl-L-methionine binding to the enzyme
C271S
-
the mutation does not affect the activity and structure of the enzyme
C334S
-
the mutation decreases the enzymatic turnover and changes the conformation of the enzyme
C360S
-
the mutation decreases the enzymatic turnover and changes the conformation of the enzyme
C375S
-
the mutation does not affect the activity and structure of the enzyme
C72S
-
the mutant is completely inactive
D102N
-
inactive
D102P
-
inactive
D150N
-
the mutant shows reduced activity compared to the wild type enzyme
D150P
-
inactive
D76N
-
inactive
D76P
-
inactive
D84N
-
inactive
D84P
-
inactive
G134A
-
the mutants activity is seriously impaired compared with that of wild type
G60A
-
inactive
G80A
-
inactive
G82A
-
the mutants activity is seriously impaired compared with that of wild type
I101A
-
inactive
L160A
-
inactive
L77A
-
the mutants activity is seriously impaired compared with that of wild type
N155A
-
inactive
R57A
-
the mutant's activity is seriously impaired compared with that of wild type
R83A
-
the mutants activity is seriously impaired compared with that of wild type
S81A
-
the mutants activity is seriously impaired compared with that of wild type
T104A
-
the mutants activity is seriously impaired compared with that of wild type
V157A
-
the mutants activity is seriously impaired compared with that of wild type
V161A
-
the mutants activity is seriously impaired compared with that of wild type
Y135A
-
the mutants activity is seriously impaired compared with that of wild type
Y58A
-
the mutants activity is seriously impaired compared with that of wild type
additional information
-
an exon-4 and -5 skipping (DELTA4,5) truncated mutant form does not convert arsenite to monomethylarsonate or dimethylarsinic acid