Information on EC 1.1.1.375 - L-2-hydroxycarboxylate dehydrogenase [NAD(P)+]

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The enzyme appears in viruses and cellular organisms

EC NUMBER
COMMENTARY hide
1.1.1.375
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RECOMMENDED NAME
GeneOntology No.
L-2-hydroxycarboxylate dehydrogenase [NAD(P)+]
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REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
a (2S)-2-hydroxycarboxylate + NAD(P)+ = a 2-oxocarboxylate + NAD(P)H + H+
show the reaction diagram
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PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
coenzyme M biosynthesis
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SYSTEMATIC NAME
IUBMB Comments
(2S)-2-hydroxycarboxylate:NAD(P)+ oxidoreductase
The enzyme from the archaeon Methanocaldococcus jannaschii catalyses the reversible oxidation of (2R)-3-sulfolactate and (S)-malate to 3-sulfopyruvate and oxaloacetate, respectively (note that (2R)-3-sulfolactate has the same stereochemical configuration as (2S)-2-hydroxycarboxylates) [1]. The enzyme can use both NADH and NADPH, although activity is higher with NADPH [1-3]. The oxidation of (2R)-3-sulfolactate was observed only in the presence of NADP+ [1]. The same organism also possesses an NAD+-specific enzyme with similar activity, cf. EC 1.1.1.337, L-2-hydroxycarboxylate dehydrogenase (NAD+).
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
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SwissProt
Manually annotated by BRENDA team
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
(2S)-3-sulfolactate + NADP+
3-sulfopyruvate + NADPH + H+
show the reaction diagram
weak activity, Vmax/KM: 1/min*mg. The enzyme does not catalyse the oxidation of (2S)-3-sulfolactate with NAD+ as cofactor
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r
(S)-malate + NAD+
oxaloacetate + NADH + H+
show the reaction diagram
(S)-malate + NADP+
oxaloacetate + NADPH + H+
show the reaction diagram
3-sulfopyruvate + NADH
(2R)-3-sulfolactate + NAD+
show the reaction diagram
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preference of NADPH over NADH
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?
3-sulfopyruvate + NADH + H+
(2S)-3-sulfolactate + NAD+
show the reaction diagram
Vmax/KM: 34/min*mg. The enzyme prefers oxaloacetate over 3-sulfopyruvate using NADH as cofactor
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ir
3-sulfopyruvate + NADPH
(2R)-3-sulfolactate + NADP+
show the reaction diagram
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the reverse oxidation reaction occurs at least ten to 20 times more slowly. Preference of NADPH over NADH
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?
3-sulfopyruvate + NADPH + H+
(2S)-3-sulfolactate + NADP+
show the reaction diagram
oxaloacetate + NADH
(S)-malate + NAD+
show the reaction diagram
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preference of NADPH over NADH
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r
oxaloacetate + NADH + H+
(S)-malate + NAD+
show the reaction diagram
oxaloacetate + NADPH
(S)-malate + NADP+
show the reaction diagram
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the reverse oxidation reaction occurs at least ten to 20 times more slowly. Preference of NADPH over NADH
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r
oxaloacetate + NADPH + H+
(S)-malate + NADP+
show the reaction diagram
pyruvate + NADH
(S)-lactate + NAD+
show the reaction diagram
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preference of NADPH over NADH. Activity is detected only when the allosteric activator fructose-1,6-bisphosphate is added to the assay mixture
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?
pyruvate + NADH + H+
(S)-lactate + NAD+
show the reaction diagram
pyruvate + NADPH
(S)-lactate + NADP+
show the reaction diagram
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preference of NADPH over NADH. Activity is detected only when the allosteric activator fructose-1,6-bisphosphate is added to the assay mixture
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?
pyruvate + NADPH + H+
(S)-lactate + NADP+
show the reaction diagram
additional information
?
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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)-malate + NAD+
oxaloacetate + NADH + H+
show the reaction diagram
3-sulfopyruvate + NADPH + H+
(2S)-3-sulfolactate + NADP+
show the reaction diagram
Q60176
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r
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
NAD(P)H
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the cofactor is bound at the active site
NAD+
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the enzyme prefers NADP+ over NAD+ in oxidation of (S)-malate
NADP+
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the enzyme prefers NADP+ over NAD+ in oxidation of (S)-malate
NADPH
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Ca2+
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in the presence of NADPH, 10 mM MgCl2, MnCl2 or CaCl2 is required to support full activity. When using NADH as coenzyme enzymatic activity is insensitive to salt concentration
K+
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in the presence of NADPH, full enzymatic activity requires a minimum salt concentration of 0.1 M NaCl or KCl. At lower salt concentrations, the activity decreases by a factor of three. When using NADH as coenzyme enzymatic activity is insensitive to salt concentration
Mg2+
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in the presence of NADPH, 10 mM MgCl2, MnCl2 or CaCl2 is required to support full activity. When using NADH as coenzyme enzymatic activity is insensitive to salt concentration
Mn2+
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in the presence of NADPH, 10 mM MgCl2, MnCl2 or CaCl2 is required to support full activity. When using NADH as coenzyme enzymatic activity is insensitive to salt concentration
Na+
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in the presence of NADPH, full enzymatic activity requires a minimum salt concentration of 0.1 M NaCl or KCl. At lower salt concentrations, the activity decreases by a factor of three. When using NADH as coenzyme enzymatic activity is insensitive to salt concentration
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
oxaloacetate
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above 0.3 mM
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
D-fructose 1,6-bisphosphate
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activates
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
4.6
(2S)-3-sulfolactate
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70C, pH 9.5, cofactor: NADP+
0.025 - 0.15
(S)-malate
0.19 - 1.3
3-sulfopyruvate
0.14
NADH
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70C, pH 8.0
0.02 - 0.2
NADPH
0.06 - 0.3
oxaloacetate
0.84
pyruvate
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pH 6.0-7.0, 45C
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7
enzymatic activity of the dimeric enzyme is controlled by a pH-dependent transition between an active and inactive dimeric state at pH 7 without dissociation of the subunits
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
PDB
SCOP
CATH
ORGANISM
UNIPROT
Methanocaldococcus jannaschii (strain ATCC 43067 / DSM 2661 / JAL-1 / JCM 10045 / NBRC 100440)
Methanocaldococcus jannaschii (strain ATCC 43067 / DSM 2661 / JAL-1 / JCM 10045 / NBRC 100440)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
57000
sedimentation analysis
113000
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sedimentation analysis
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
dimer
the effects of high temperature, cofactor binding, and high phosphate concentration are studied. They do not modify the oligomeric state of the enzyme. Enzymatic activity of the dimeric enzyme is controlled by a pH-dependent transition at pH 7 without dissociation of the subunits
tetramer
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
the three-dimensional structure is determined in two crystal forms: a dimeric structure in the orthorhombic crystal at 1.9 A resolution and a structure in the tetragonal crystal at 2.8 A; the three-dimensional structure of its gene product has been determined in two crystal forms: a dimeric structure in the orthorhombic crystal at 1.9 A resolution and a tetrameric structure in the tetragonal crystal at 2.8 A
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TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
80
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thermal transition between active and inactive enzyme starts at about 80C and follows first-order kinetics
ORGANIC SOLVENT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
guanidine-HCl
OXIDATION STABILITY
ORGANISM
UNIPROT
LITERATURE
the enzyme is not sensitive to oxygen
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728317
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expression in Escherichia coli
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overexpressed in Escherichia coli
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