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Information on EC 1.1.1.428 - 4-methylthio 2-oxobutanoate reductase (NADH)
for references in articles please use BRENDA:EC1.1.1.428
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EC Tree 1 Oxidoreductases
1.1 Acting on the CH-OH group of donors
1.1.1 With NAD+ or NADP+ as acceptor
1.1.1.428 4-methylthio 2-oxobutanoate reductase (NADH)
IUBMB Comments
The substrate of this enzyme is formed as an intermediate during L-methionine salvage from S-methyl-5′-thioadenosine, which is formed during the biosynthesis of polyamines. The human enzyme also functions as a transcriptional co-regulator that downregulates the expression of many tumor-suppressor genes, thus providing a link between gene repression and the methionine salvage pathway. A similar, but NADP-specific, enzyme is involved in dimethylsulfoniopropanoate biosynthesis in algae and phytoplankton.
The expected taxonomic range for this enzyme is: Homo sapiens
Reaction Schemes
showSynonyms
ctbp2, ctbp1, c-terminal binding protein 1, c-terminal-binding protein 2, c-terminal-binding protein 1, more
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
4-methylthio 2-oxobutyrate reductase
-
-
-
-
4-methylthio 2-oxobutyric acid reductase
-
-
-
-
C-terminal-binding protein 1
CTBP1
MTOB reductase
-
-
-
-
C-terminal-binding protein 1
-
-
-
-
CTBP1
-
-
-
-
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
(2R)-2-hydroxy-4-(methylsulfanyl)butanoate + NAD+ = 4-(methylsulfanyl)-2-oxobutanoate + NADH + H+
-
-
-
-
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SYSTEMATIC NAME
IUBMB Comments
(2R)-2-hydroxy-4-(methylsulfanyl)butanoate:NAD+ 2-oxidoreductase
The substrate of this enzyme is formed as an intermediate during L-methionine salvage from S-methyl-5'-thioadenosine, which is formed during the biosynthesis of polyamines. The human enzyme also functions as a transcriptional co-regulator that downregulates the expression of many tumor-suppressor genes, thus providing a link between gene repression and the methionine salvage pathway. A similar, but NADP-specific, enzyme is involved in dimethylsulfoniopropanoate biosynthesis in algae and phytoplankton.
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
2-oxocaproate + NADH + H+
?
-
Substrates: 1040% activity compared to pyruvate
Products: -
Products: -
?
2-oxogluconate + NADH + H+
?
-
Substrates: 20% activity compared to pyruvate
Products: -
Products: -
?
2-oxoglutarate + NADH + H+
?
-
Substrates: 80% activity compared to pyruvate
Products: -
Products: -
?
2-oxoisocaproate + NADH + H+
?
-
Substrates: 430% activity compared to pyruvate
Products: -
Products: -
?
2-oxovalerate + NADH + H+
?
-
Substrates: 160% activity compared to pyruvate
Products: -
Products: -
?
3-phosphohydroxypyruvate + NADH + H+
?
-
Substrates: 10% activity compared to pyruvate
Products: -
Products: -
?
4-(methylsulfanyl)-2-oxobutanoate + NADH + H+
(2R)-2-hydroxy-4-(methylsulfanyl)butanoate + NAD+
glyoxylate + NADH + H+
?
-
Substrates: 350% activity compared to pyruvate
Products: -
Products: -
?
oxaloacetate + NADH + H+
?
-
Substrates: 30% activity compared to pyruvate
Products: -
Products: -
?
phenylpyruvate + NADH + H+
?
-
Substrates: 420% activity compared to pyruvate
Products: -
Products: -
?
4-(methylsulfanyl)-2-oxobutanoate + NADH + H+
(2R)-2-hydroxy-4-(methylsulfanyl)butanoate + NAD+
-
Substrates: -
Products: -
Products: -
?
4-(methylsulfanyl)-2-oxobutanoate + NADH + H+
(2R)-2-hydroxy-4-(methylsulfanyl)butanoate + NAD+
Substrates: -
Products: -
Products: -
?
4-(methylsulfanyl)-2-oxobutanoate + NADH + H+
(2R)-2-hydroxy-4-(methylsulfanyl)butanoate + NAD+
-
Substrates: best substrate, 8120% activity compared to pyruvate
Products: -
Products: -
?
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
4-(methylsulfanyl)-2-oxobutanoate + NADH + H+
(2R)-2-hydroxy-4-(methylsulfanyl)butanoate + NAD+
4-(methylsulfanyl)-2-oxobutanoate + NADH + H+
(2R)-2-hydroxy-4-(methylsulfanyl)butanoate + NAD+
-
Substrates: -
Products: -
Products: -
?
4-(methylsulfanyl)-2-oxobutanoate + NADH + H+
(2R)-2-hydroxy-4-(methylsulfanyl)butanoate + NAD+
Substrates: -
Products: -
Products: -
?
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
4-(methylsulfanyl)-2-oxobutanoate
substrate inhibition; substrate inhibition
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kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.1
2-(hydroxyimino)-3-(2-methoxyphenyl)propanoic acid
Homo sapiens
-
IC50 above 0.1 mM, at pH 7.1 and 25°C
-
0.00072
2-(hydroxyimino)-3-(3-hydroxyphenyl)propanoic acid
Homo sapiens
-
at pH 7.1 and 25°C
-
0.00088
2-(hydroxyimino)-3-(3-methoxyphenyl)propanoic acid
Homo sapiens
-
at pH 7.1 and 25°C
-
0.00734
2-(hydroxyimino)-3-(4-hydroxyphenyl)propanoic acid
Homo sapiens
-
at pH 7.1 and 25°C
-
0.00216
2-(hydroxyimino)-3-(4-methoxyphenyl)propanoic acid
Homo sapiens
-
at pH 7.1 and 25°C
-
0.00765
3-(2-chlorophenyl)-2-(hydroxyimino)propanoic acid
Homo sapiens
-
at pH 7.1 and 25°C
-
0.00017
3-(3-chlorophenyl)-2-(hydroxyimino)propanoic acid
Homo sapiens
-
at pH 7.1 and 25°C
-
0.00018
3-(4-chlorophenyl)-2-(hydroxyimino)propanoic acid
Homo sapiens
-
at pH 7.1 and 25°C
-
0.000745
2-(hydroxyimino)-3-phenylpropanoic acid
Homo sapiens
-
pH and temperature not specified in the publication
-
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
Highest Expressing Human Cell Lines
Cell Line LinksPlease wait a moment until the data is sorted. This message will disappear when the data is sorted.
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). Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CtBP1 in complex with 4-(methylsulfanyl)-2-oxobutanoate and NAD+, hanging drop vapor diffusion method, using 200-300 mM magnesium chloride, 0-140 mM sodium formate, 100 mM HEPES pH 7.5, and 2.5 mM NAD+
CtBP2 in complex with 4-(methylsulfanyl)-2-oxobutanoate and NAD+, hanging drop vapor diffusion method, using 200 mM, potassium nitrate, 15-20% PEG 3350, and 100 mM bis-tris-propane pH 7.0
enzyme in complex with phenylpyruvate is crystallized by hanging drop vapor diffusion against a reservoir solution containing 200 mM CaCl2, 100 mM HEPES pH 7.5, and 2.5 mM NAD+. Enzyme in complex with 2-hydroxyimino-3-phenylpropanoic acid is crystallized by vapor diffusion against a reservoir solution containing 75 mM CaCl2, 100 mM HEPES pH 7.5, and 1 mM NADH
-
selenomethionine-substituted enzyme bound to NAD+, using 140 mM sodium formate, 70 mM magnesium acetate, and 100 mM HEPES (pH 7.0)
-
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
D204A/G181V/G183V
-
the mutations strongly inhibit the enzyme's ability to bind E1A and NAD+. The mutant is defective in catalysis
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Hilbert, B.J.; Morris, B.L.; Ellis, K.C.; Paulsen, J.L.; Schiffer, C.A.; Grossman, S.R.; Royer, W.E.
Structure-guided design of a high affinity inhibitor to human CtBP
ACS Chem. Biol.
10
1118-1127
2015
Homo sapiens
brenda
Achouri, Y.; Noel, G.; Van Schaftingen, E.
2-Keto-4-methylthiobutyrate, an intermediate in the methionine salvage pathway, is a good substrate for CtBP1
Biochem. Biophys. Res. Commun.
352
903-906
2007
Homo sapiens
brenda
Korwar, S.; Morris, B.; Parikh, H.; Coover, R.; Doughty, T.; Love, I.; Hilbert, B.; Royer, W.J.; Kellogg, G.; Grossman, S.; Ellis, K.
Design, synthesis, and biological evaluation of substrate-competitive inhibitors of C-terminal binding protein (CtBP)
Bioorg. Med. Chem.
24
2707-2715
2016
Homo sapiens
brenda
Hilbert, B.J.; Grossman, S.R.; Schiffer, C.A.; Royer, W.E.
Crystal structures of human CtBP in complex with substrate MTOB reveal active site features useful for inhibitor design
FEBS Lett.
588
1743-1748
2014
Homo sapiens (P56545), Homo sapiens (Q13363), Homo sapiens
brenda
Kumar, V.; Carlson, J.; Ohgi, K.; Edwards, T.; Rose, D.; Escalante, C.; Rosenfeld, M.; Aggarwal, A.
Transcription corepressor CtBP is an NAD+-regulated dehydrogenase
Mol. Cell.
10
857-869
2002
Homo sapiens
brenda
EXTERNAL LINKS (specific for EC-Number 1.1.1.428)
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Release 2023.1 (January 2023)
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