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Information on EC 2.1.1.281 - phenylpyruvate C3-methyltransferase
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EC Tree
2.1.1.281 phenylpyruvate C3-methyltransferaseIUBMB Comments
The enzyme from the bacterium Streptomyces hygroscopicus NRRL3085 is involved in synthesis of the nonproteinogenic amino acid (2S,3S)-beta-methyl-phenylalanine, a building block of the antibiotic mannopeptimycin.
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The enzyme appears in viruses and cellular organisms
Reaction Schemes
Synonyms
C-MT, ELQ87_35210, MppJ, MT SgvM, phenylpyruvate Cbeta-methyltransferase, phenylpyruvate methyltransferase, S-adenosylmethionine-dependent methyltransferase, SgvM, 
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
MppJ
phenylpyruvate Cbeta-methyltransferase
phenylpyruvate methyltransferase
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
S-adenosyl-L-methionine + 3-phenylpyruvate = S-adenosyl-L-homocysteine + (3S)-2-oxo-3-phenylbutanoate
S-adenosyl-L-methionine + 3-phenylpyruvate = S-adenosyl-L-homocysteine + (3S)-2-oxo-3-phenylbutanoate
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-
-
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S-adenosyl-L-methionine + 3-phenylpyruvate = S-adenosyl-L-homocysteine + (3S)-2-oxo-3-phenylbutanoate
the enzyme methylates the benzylic C atom of phenylpyruvate to give 3-methylpyruvate, reaction mechanism, structure-function analysis, overview
S-adenosyl-L-methionine + 3-phenylpyruvate = S-adenosyl-L-homocysteine + (3S)-2-oxo-3-phenylbutanoate
the enzyme methylates the benzylic C atom of phenylpyruvate to give 3-methylpyruvate, reaction mechanism, structure-function analysis, overview
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SYSTEMATIC NAME
IUBMB Comments
S-adenosyl-L-methionine:2-oxo-3-phenylpropanoate C3-methyltransferase
The enzyme from the bacterium Streptomyces hygroscopicus NRRL3085 is involved in synthesis of the nonproteinogenic amino acid (2S,3S)-beta-methyl-phenylalanine, a building block of the antibiotic mannopeptimycin.
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
S-adenosyl-L-ethionine + 2-oxobutyrate
S-adenosyl-L-homocysteine + (3S)-methyl-2-oxovalerate
-
-
-
?
S-adenosyl-L-methionine + 2-oxo-3-phenylpropanoate
S-adenosyl-L-homocysteine + (3S)-2-oxo-3-methyl-3-phenylpropanoate
S-adenosyl-L-methionine + 2-oxobutyrate
S-adenosyl-L-homocysteine + 3-methyl-2-oxobutyrate
-
-
-
?
S-adenosyl-L-methionine + 2-oxovalerate
S-adenosyl-L-homocysteine + (3R)-methyl-2-oxovalerate
-
-
-
?
S-adenosyl-L-methionine + 3-phenylpyruvate
S-adenosyl-L-homocysteine + (3R)-2-oxo-3-phenylbutanoate
S-adenosyl-L-methionine + 3-phenylpyruvate
S-adenosyl-L-homocysteine + (3S)-2-oxo-3-phenylbutanoate
-
-
-
?
S-adenosyl-L-methionine + 4-methyl-2-oxovalerate
S-adenosyl-L-homocysteine + 3,4-dimethyl-2-oxovalerate
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-
-
?
S-adenosyl-L-methionine + 4-methyl-2-oxovalerate
S-adenosyl-L-homocysteine + ?
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-
-
?
S-adenosyl-L-methionine + pyruvate
S-adenosyl-L-homocysteine + 2-oxobutyrate
SgvM-catalyzed 13C-dimethylation of pyruvate in two steps results in formation of 3-methyl-2-oxobutyrate
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-
?
S-adenosyl-L-methionine + 2-oxo-3-phenylpropanoate
S-adenosyl-L-homocysteine + (3S)-2-oxo-3-methyl-3-phenylpropanoate
-
the enzyme is involved in synthesis of the nonproteinogenic amino acid (2S,3S)-beta-methyl-phenylalanine, a building block of the glycopeptide antibiotic mannopeptimycin
-
-
?
S-adenosyl-L-methionine + 2-oxo-3-phenylpropanoate
S-adenosyl-L-homocysteine + (3S)-2-oxo-3-methyl-3-phenylpropanoate
-
2-oxo-3-phenylpropanoate i.e. 3-phenylpyruvate. S-Adenosyl-L-methionine has higher binding affinity for the enzyme than 2-oxo-3-phenylpropanoate, and the C-C bond formation in (3S)-2-oxo-3-methyl-3-phenylpropanoate might be the rate-limiting step, as opposed to the C-S bond breakage in S-adenosyl-L-methionine. No enzyme activity on glutamic acid, cinnamic acid, phenyl acetic acid and benzoyl acetic acid. The alpha-keto and beta-phenyl functional groups are crucial in MppJ molecular recognition. The enzyme strictly transfers a methyl group from S-adenosyl-L-methionine the beta position of 2-oxo-3-phenylpropanoate
(3S)-2-oxo-3-methyl-3-phenylpropanoate i.e. (3S)-beta-methyl-phenylpyruvate
-
?
S-adenosyl-L-methionine + 2-oxo-3-phenylpropanoate
S-adenosyl-L-homocysteine + (3S)-2-oxo-3-methyl-3-phenylpropanoate
-
the enzyme is involved in synthesis of the nonproteinogenic amino acid (2S,3S)-beta-methyl-phenylalanine, a building block of the glycopeptide antibiotic mannopeptimycin
-
-
?
S-adenosyl-L-methionine + 2-oxo-3-phenylpropanoate
S-adenosyl-L-homocysteine + (3S)-2-oxo-3-methyl-3-phenylpropanoate
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2-oxo-3-phenylpropanoate i.e. 3-phenylpyruvate. S-Adenosyl-L-methionine has higher binding affinity for the enzyme than 2-oxo-3-phenylpropanoate, and the C-C bond formation in (3S)-2-oxo-3-methyl-3-phenylpropanoate might be the rate-limiting step, as opposed to the C-S bond breakage in S-adenosyl-L-methionine. No enzyme activity on glutamic acid, cinnamic acid, phenyl acetic acid and benzoyl acetic acid. The alpha-keto and beta-phenyl functional groups are crucial in MppJ molecular recognition. The enzyme strictly transfers a methyl group from S-adenosyl-L-methionine the beta position of 2-oxo-3-phenylpropanoate
(3S)-2-oxo-3-methyl-3-phenylpropanoate i.e. (3S)-beta-methyl-phenylpyruvate
-
?
S-adenosyl-L-methionine + 3-phenylpyruvate
S-adenosyl-L-homocysteine + (3R)-2-oxo-3-phenylbutanoate
phenylpyruvate binding structure analysis
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-
?
S-adenosyl-L-methionine + 3-phenylpyruvate
S-adenosyl-L-homocysteine + (3R)-2-oxo-3-phenylbutanoate
Arg127 is electrostatically associated with phenylpyruvate, binding structure analysis, enzyme MppJ is an R-configuration-specific methyltransferase, ratios of 5:1 and 1:1 for (2S,3R)-betaMePhe versus (2S,3S)-betaMePhe
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-
?
S-adenosyl-L-methionine + 3-phenylpyruvate
S-adenosyl-L-homocysteine + (3R)-2-oxo-3-phenylbutanoate
phenylpyruvate binding structure analysis
-
-
?
S-adenosyl-L-methionine + 3-phenylpyruvate
S-adenosyl-L-homocysteine + (3R)-2-oxo-3-phenylbutanoate
Arg127 is electrostatically associated with phenylpyruvate, binding structure analysis, enzyme MppJ is an R-configuration-specific methyltransferase, ratios of 5:1 and 1:1 for (2S,3R)-betaMePhe versus (2S,3S)-betaMePhe
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-
?
additional information
?
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aside from its physiological substrate 4-methyl-2-oxovalerate, enzyme SgvM catalyzes the (di)methylation of pyruvate, 2-oxobutyrate, 2-oxovalerate, and phenylpyruvate at the beta-carbon atom. SgvM acts stereoselectively. SgvM also catalyzes stereoselective ethylation reactions with S-adenosylethionine as the electrophile. The methylation of 2-oxovalerate occurs with R selectivity while the ethylation of 2-oxobutyrate with S-adenosylethionine results in the S enantiomer of 3-methyl-2-oxovalerate. Product analysis by 13C NMR spectroscopy
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additional information
?
-
the enzyme has no nonheme oxygenase activity
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-
?
additional information
?
-
the enzyme has no nonheme oxygenase activity
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-
?
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
S-adenosyl-L-methionine + 2-oxo-3-phenylpropanoate
S-adenosyl-L-homocysteine + (3S)-2-oxo-3-methyl-3-phenylpropanoate
S-adenosyl-L-methionine + 3-phenylpyruvate
S-adenosyl-L-homocysteine + (3R)-2-oxo-3-phenylbutanoate
S-adenosyl-L-methionine + 3-phenylpyruvate
S-adenosyl-L-homocysteine + (3S)-2-oxo-3-phenylbutanoate
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-
-
?
S-adenosyl-L-methionine + 4-methyl-2-oxovalerate
S-adenosyl-L-homocysteine + ?
-
-
-
?
S-adenosyl-L-methionine + 2-oxo-3-phenylpropanoate
S-adenosyl-L-homocysteine + (3S)-2-oxo-3-methyl-3-phenylpropanoate
-
the enzyme is involved in synthesis of the nonproteinogenic amino acid (2S,3S)-beta-methyl-phenylalanine, a building block of the glycopeptide antibiotic mannopeptimycin
-
-
?
S-adenosyl-L-methionine + 2-oxo-3-phenylpropanoate
S-adenosyl-L-homocysteine + (3S)-2-oxo-3-methyl-3-phenylpropanoate
-
the enzyme is involved in synthesis of the nonproteinogenic amino acid (2S,3S)-beta-methyl-phenylalanine, a building block of the glycopeptide antibiotic mannopeptimycin
-
-
?
S-adenosyl-L-methionine + 3-phenylpyruvate
S-adenosyl-L-homocysteine + (3R)-2-oxo-3-phenylbutanoate
phenylpyruvate binding structure analysis
-
-
?
S-adenosyl-L-methionine + 3-phenylpyruvate
S-adenosyl-L-homocysteine + (3R)-2-oxo-3-phenylbutanoate
phenylpyruvate binding structure analysis
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-
?
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
physiological function
S-adenosylmethionine-dependent methyltransferases (MTs) play a decisive role in the biosynthesis of natural products and in epigenetic processes. MTs catalyze the methylation of heteroatoms and even of carbon atoms, which, in many cases, is a challenging reaction in conventional synthesis. C-MTs are often highly substrate-specific. SgvM from Streptomyces griseoviridis features an extended substrate scope with respect to the nucleophile as well as the electrophile. It catalyze the transfer of the electrophilic methyl group of SAM to the C3 position of 4-methyl-2-oxovalerate (alpha-ketoleucine)
additional information
evolution
enzyme MppJ is structurally related to the MT protein family
evolution
-
enzyme MppJ is structurally related to the MT protein family
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additional information
the enzyme is composed of two domains: a dimerization domain (DD) and a methyltransfer domain (MT). The substrate-binding pocket is situated at the occlusion of the DD and MT domains, in which the iron centre is solvent-accessible
additional information
-
the enzyme is composed of two domains: a dimerization domain (DD) and a methyltransfer domain (MT). The substrate-binding pocket is situated at the occlusion of the DD and MT domains, in which the iron centre is solvent-accessible
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UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). A0A1J5QAD0_9ZZZZ
341
1
36970
TrEMBL
other Location (Reliability: 5)
A0A6M1ZUH7_9BACT
332
0
37558
TrEMBL
-
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
homodimer
homodimer
2 * 38000, recombinant His6-tagged enzyme, SDS-PAGE
homodimer
-
2 * 38000, recombinant His6-tagged enzyme, SDS-PAGE
-
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CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
purified recombinant His6-tagged enzyme, in apoform or in complex with S-adenosyl-L-methionine and phenylpyruvate, hanging drop vapour diffusion technique, mixing of 0.001 ml of 24 mg/ml protein in 50 mM HEPES, pH 7.5, 100 mM CaCl2, with 0.001 ml of reservoir solution containing 16% PEG 3350, 200 mM NaI, 20°C, 10 days, X-ray diffraction structure determination and analysis at 2.0-2.5 A resolution, molecular replacement. From the collected crystal diffraction data four additional structures of MppJ in complex with phenlpyruvate, 4-hydroxyphenylpyruvate, S-adenosyl-L-methionine and phenylpyruvate or S-adenosyl-L-homocysteine and methylphenylpyruvate, although crystals of the apo form remain unobtainable
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
C319A
site-directed mutagenesis, the mutant shows 39% reduced activity compared to the wild-type enzyme
D244E
site-directed mutagenesis, the mutant enzyme shows altered conformation and substrate binding structure compared to the wild-type enzyme
D244L
site-directed mutagenesis, the mutant enzyme shows altered conformation and substrate binding structure compared to the wild-type enzyme
R127L/D244E
site-directed mutagenesis, the mutant enzyme shows altered conformation and substrate binding structure compared to the wild-type enzyme
W99F
the mutant shows altered stereochemistry in the reaction compared to the wild-type enzyme
C319A
-
site-directed mutagenesis, the mutant shows 39% reduced activity compared to the wild-type enzyme
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D244E
-
site-directed mutagenesis, the mutant enzyme shows altered conformation and substrate binding structure compared to the wild-type enzyme
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D244L
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site-directed mutagenesis, the mutant enzyme shows altered conformation and substrate binding structure compared to the wild-type enzyme
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R127L/D244E
-
site-directed mutagenesis, the mutant enzyme shows altered conformation and substrate binding structure compared to the wild-type enzyme
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W99F
-
the mutant shows altered stereochemistry in the reaction compared to the wild-type enzyme
-
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant N-terminally His6-tagged enzyme by nickel affinity chromatography, ion-exchange chromatography, and ultrafiltration
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
gene ELQ87_35210, the MT SgvM locates in the biosynthetic gene cluster of the octadepsipeptide antibiotic viridogrisein
gene mppJ from the mannopeptimycin-biosynthetic gene cluster, DNA and amino acid sequence determination and analysis, recombinant expression of N-terminally His6-tagged enzyme
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
synthesis
the nonenzymatic stereoselective formation of C-C bonds by methylation is challenging and usually requires multistep syntheses. In contrast, the asymmetric introduction of a methyl group in natural product biosynthesis is performed in a single step and catalyzed by methyltransferases (MTs), which usually require S-adenosylmethionine (SAM) as the methyl donor. Enzyme SgvM might be a valuable tool for asymmetric biocatalytic C-alkylation reactions. It catalyze the transfer of the electrophilic methyl group of SAM to the C3 position
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Huang, Y.T.; Lyu, S.Y.; Chuang, P.H.; Hsu, N.S.; Li, Y.S.; Chan, H.C.; Huang, C.J.; Liu, Y.C.; Wu, C.J.; Yang, W.B.; Li, T.L.
In vitro characterization of enzymes involved in the synthesis of nonproteinogenic residue (2S,3S)-beta-methylphenylalanine in glycopeptide antibiotic mannopeptimycin
ChemBioChem
10
2480-2487
2009
Streptomyces hygroscopicus, Streptomyces hygroscopicus NRRL3085
brenda
Zou, X.W.; Liu, Y.C.; Hsu, N.S.; Huang, C.J.; Lyu, S.Y.; Chan, H.C.; Chang, C.Y.; Yeh, H.W.; Lin, K.H.; Wu, C.J.; Tsai, M.D.; Li, T.L.
Structure and mechanism of a nonhaem-iron SAM-dependent C-methyltransferase and its engineering to a hydratase and an O-methyltransferase
Acta Crystallogr. Sect. D
70
1549-1560
2014
Streptomyces hygroscopicus (Q643C8), Streptomyces hygroscopicus NRRL3085 (Q643C8)
brenda
Sommer-Kamann, C.; Fries, A.; Mordhorst, S.; Andexer, J.N.; Mueller, M.
Asymmetric C-alkylation by the S-adenosylmethionine-dependent methyltransferase SgvM
Angew. Chem. Int. Ed. Engl.
56
4033-4036
2017
Streptomyces griseoviridis (A0A3Q9KTF8)
brenda
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Release 2023.1 (January 2023)
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