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Information on EC 1.1.1.375 - L-2-hydroxycarboxylate dehydrogenase [NAD(P)+]
for references in articles please use BRENDA:EC1.1.1.375
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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
1.1.1.375 L-2-hydroxycarboxylate dehydrogenase [NAD(P)+]
IUBMB Comments
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) . 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+ . The same organism also possesses an NAD+-specific enzyme with similar activity, cf. EC 1.1.1.337, L-2-hydroxycarboxylate dehydrogenase (NAD+).
The enzyme appears in viruses and cellular organisms
- 1.1.1.375
- dehydrogenases
-
methanococcus
- jannaschii
- l-lactate
-
nadh-dependent
-
hyperthermophilic
showSynonyms
lactate/malate dehydrogenase, mj0490, ldh-like l-maldh, more
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
lactate/malate dehydrogenase
LDH-like L-MalDH
MdhII
MJ0409
MJ0490
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
a (2S)-2-hydroxycarboxylate + NAD(P)+ = a 2-oxocarboxylate + NAD(P)H + H+
-
-
-
-
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PATHWAY SOURCE
PATHWAYS
BRENDA
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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+).
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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
(2S)-3-sulfolactate + NADP+
3-sulfopyruvate + NADPH + H+
Substrates: weak activity, Vmax/KM: 1/min*mg. The enzyme does not catalyse the oxidation of (2S)-3-sulfolactate with NAD+ as cofactor
Products: -
Products: -
r
3-sulfopyruvate + NADH + H+
(2S)-3-sulfolactate + NAD+
Substrates: Vmax/KM: 34/min*mg. The enzyme prefers oxaloacetate over 3-sulfopyruvate using NADH as cofactor
Products: -
Products: -
ir
3-sulfopyruvate + NADPH
(2R)-3-sulfolactate + NADP+
Substrates: the reverse oxidation reaction occurs at least ten to 20 times more slowly. Preference of NADPH over NADH
Products: -
Products: -
?
pyruvate + NADH
(S)-lactate + NAD+
Substrates: preference of NADPH over NADH. Activity is detected only when the allosteric activator fructose-1,6-bisphosphate is added to the assay mixture
Products: -
Products: -
?
pyruvate + NADPH
(S)-lactate + NADP+
Substrates: preference of NADPH over NADH. Activity is detected only when the allosteric activator fructose-1,6-bisphosphate is added to the assay mixture
Products: -
Products: -
?
(S)-malate + NAD+
oxaloacetate + NADH + H+
Substrates: -
Products: -
Products: -
?
(S)-malate + NAD+
oxaloacetate + NADH + H+
Substrates: -
Products: -
Products: -
?
(S)-malate + NAD+
oxaloacetate + NADH + H+
Substrates: Vmax/KM: 4/min*mg. The enzyme prefers NADP+ over NAD+ in oxidation of (S)-malate
Products: -
Products: -
r
(S)-malate + NAD+
oxaloacetate + NADH + H+
Substrates: Vmax/KM: 4/min*mg. The enzyme prefers NADP+ over NAD+ in oxidation of (S)-malate
Products: -
Products: -
r
(S)-malate + NAD+
oxaloacetate + NADH + H+
Substrates: -
Products: -
Products: -
?
(S)-malate + NADP+
oxaloacetate + NADPH + H+
Substrates: Vmax/KM: 110/min*mg. The enzyme prefers NADP+ over NAD+ in oxidation of (S)-malate
Products: -
Products: -
r
(S)-malate + NADP+
oxaloacetate + NADPH + H+
Substrates: Vmax/KM: 110/min*mg. The enzyme prefers NADP+ over NAD+ in oxidation of (S)-malate
Products: -
Products: -
r
3-sulfopyruvate + NADH
(2R)-3-sulfolactate + NAD+
Substrates: preference of NADPH over NADH
Products: -
Products: -
?
3-sulfopyruvate + NADH
(2R)-3-sulfolactate + NAD+
Substrates: preference of NADPH over NADH
Products: -
Products: -
?
3-sulfopyruvate + NADPH + H+
(2S)-3-sulfolactate + NADP+
Substrates: -
Products: -
Products: -
r
3-sulfopyruvate + NADPH + H+
(2S)-3-sulfolactate + NADP+
Substrates: Vmax/KM: 590/min*mg. The enzyme prefers NADPH over NADH in reduction of 3-sulfopyruvate
Products: -
Products: -
r
oxaloacetate + NADH
(S)-malate + NAD+
Substrates: preference of NADPH over NADH
Products: -
Products: -
r
oxaloacetate + NADH
(S)-malate + NAD+
Substrates: preference of NADPH over NADH
Products: -
Products: -
r
oxaloacetate + NADH + H+
(S)-malate + NAD+
Substrates: -
Products: -
Products: -
r
oxaloacetate + NADH + H+
(S)-malate + NAD+
Substrates: Vmax/KM: 120 /min*mg. The enzyme prefers oxaloacetate over 3-sulfopyruvate using NADH as cofactor. The enzyme prefers NADPH over NADH in reduction of oxaloacetate
Products: -
Products: -
r
oxaloacetate + NADH + H+
(S)-malate + NAD+
Substrates: Vmax/KM: 120 /min*mg. The enzyme prefers oxaloacetate over 3-sulfopyruvate using NADH as cofactor. The enzyme prefers NADPH over NADH in reduction of oxaloacetate
Products: -
Products: -
r
oxaloacetate + NADH + H+
(S)-malate + NAD+
Substrates: -
Products: -
Products: -
r
oxaloacetate + NADPH
(S)-malate + NADP+
Substrates: the reverse oxidation reaction occurs at least ten to 20 times more slowly. Preference of NADPH over NADH
Products: -
Products: -
r
oxaloacetate + NADPH
(S)-malate + NADP+
Substrates: the reverse oxidation reaction occurs at least ten to 20 times more slowly. Preference of NADPH over NADH
Products: -
Products: -
r
oxaloacetate + NADPH + H+
(S)-malate + NADP+
Substrates: -
Products: -
Products: -
r
oxaloacetate + NADPH + H+
(S)-malate + NADP+
Substrates: Vmax/KM: 160/min*mg. The enzyme prefers NADPH over NADH in reduction of oxaloacetate
Products: -
Products: -
r
oxaloacetate + NADPH + H+
(S)-malate + NADP+
Substrates: Vmax/KM: 160/min*mg. The enzyme prefers NADPH over NADH in reduction of oxaloacetate
Products: -
Products: -
r
oxaloacetate + NADPH + H+
(S)-malate + NADP+
Substrates: -
Products: -
Products: -
r
pyruvate + NADH + H+
(S)-lactate + NAD+
Substrates: ratio of reaction rates for NADPH and NADH is 1.3-1.6 in the temperature range of 30-60°C (with 0.4 mM fructose 1,6-bisphosphate). The enzymatic activity for the oxidation reaction can not be measured under the tested conditions
Products: -
Products: -
ir
pyruvate + NADH + H+
(S)-lactate + NAD+
Substrates: ratio of reaction rates for NADPH and NADH is 1.3-1.6 in the temperature range of 30-60°C (with 0.4 mM fructose 1,6-bisphosphate). The enzymatic activity for the oxidation reaction can not be measured under the tested conditions
Products: -
Products: -
ir
pyruvate + NADPH + H+
(S)-lactate + NADP+
Substrates: ratio of reaction rates for NADPH and NADH is 1.3-1.6 in the temperature range of 30-60°C (with 0.4 mM fructose 1,6-bisphosphate). The enzymatic activity for the oxidation reaction can not be measured under the tested conditions
Products: -
Products: -
ir
pyruvate + NADPH + H+
(S)-lactate + NADP+
Substrates: ratio of reaction rates for NADPH and NADH is 1.3-1.6 in the temperature range of 30-60°C (with 0.4 mM fructose 1,6-bisphosphate). The enzymatic activity for the oxidation reaction can not be measured under the tested conditions
Products: -
Products: -
ir
additional information
?
-
Substrates: no activity with 2-oxoglutarate and 1-oxo-1,3,4,6-hexanetetracarboxylic acid
Products: -
Products: -
?
additional information
?
-
-
Substrates: no activity with 2-oxoglutarate and 1-oxo-1,3,4,6-hexanetetracarboxylic acid
Products: -
Products: -
?
additional information
?
-
Substrates: no activity with 2-oxoglutarate and 1-oxo-1,3,4,6-hexanetetracarboxylic acid
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
3-sulfopyruvate + NADPH + H+
(2S)-3-sulfolactate + NADP+
Substrates: -
Products: -
Products: -
r
(S)-malate + NAD+
oxaloacetate + NADH + H+
Substrates: -
Products: -
Products: -
?
(S)-malate + NAD+
oxaloacetate + NADH + H+
Substrates: -
Products: -
Products: -
?
(S)-malate + NAD+
oxaloacetate + NADH + H+
Substrates: -
Products: -
Products: -
?
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
NAD+
preference of NADP(H) over NAD(H). The cofactor preference is explained by the presence of a glycine residue in the cofactor binding pocket (Gly33), which replaces a conserved aspartate (or glutamate) residue in other NAD-dependent L-lactate dehydrogenases or malate dehydrogenases
NAD+
the enzyme prefers NADP+ over NAD+ in oxidation of (S)-malate
NADH
preference of NADP(H) over NAD(H).. The ratio of reaction rates for NADPH and NADH is 1.3-1.6 in the temperature range of 30-60°C. The cofactor preference is explained by the presence of a glycine residue in the cofactor binding pocket (Gly33), which replaces a conserved aspartate (or glutamate) residue in other NAD-dependent L-lactate dehydrogenases or malate dehydrogenases
NADH
preference of NADPH over NADH. The cofactor NADP(H) is bound at the active site
NADH
the enzyme prefers NADPH over NADH in reduction of oxaloacetate
NADP+
preference of NADP(H) over NAD(H). The cofactor preference is explained by the presence of a glycine residue in the cofactor binding pocket (Gly33), which replaces a conserved aspartate (or glutamate) residue in other NAD-dependent L-lactate dehydrogenases or malate dehydrogenases
NADP+
the enzyme prefers NADP+ over NAD+ in oxidation of (S)-malate
NADPH
preference of NADP(H) over NAD(H). The ratio of reaction rates for NADPH and NADH is 1.3-1.6 in the temperature range of 30-60°C. The cofactor preference is explained by the presence of a glycine residue in the cofactor binding pocket (Gly33), which replaces a conserved aspartate (or glutamate) residue in other NAD-dependent L-lactate dehydrogenases or malate dehydrogenases
NADPH
preference of NADPH over NADH. The cofactor NADP(H) is bound at the active site
NADPH
the enzyme prefers NADPH over NADH in reduction of oxaloacetate or 3-sulfopyruvate
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ca2+
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+
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+
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+
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+
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
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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pH RANGE
ORGANISM
UNIPROT
COMMENTARY
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
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
70
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
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). MDH_METJA
Methanocaldococcus jannaschii (strain ATCC 43067 / DSM 2661 / JAL-1 / JCM 10045 / NBRC 100440)
313
0
34609
Swiss-Prot
-
MDH_ARCFU
Archaeoglobus fulgidus (strain ATCC 49558 / DSM 4304 / JCM 9628 / NBRC 100126 / VC-16)
294
0
31874
Swiss-Prot
-
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
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
tetramer
the effects of high temperature, cofactor binding, and high phosphate concentration are studied. They do not modify the oligomeric state of the enzyme
tetramer
-
the effects of high temperature, cofactor binding, and high phosphate concentration are studied. They do not modify the oligomeric state of the enzyme
-
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CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
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
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
LITERATURE
80
thermal transition between active and inactive enzyme starts at about 80°C and follows first-order kinetics
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ORGANIC SOLVENT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
guanidine-HCl
guanidine-HCl
transition between folded and unfolded enzyme (monitored by the change in molar ellipticity at 222 nm) is found at 2 M guanidine hydrochloride
guanidine-HCl
-
transition between folded and unfolded enzyme (monitored by the change in molar ellipticity at 222 nm) is found at 2 M guanidine hydrochloride
-
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OXIDATION STABILITY
ORGANISM
UNIPROT
LITERATURE
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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
Graupner, M.; Xu, H.; White, R.H.
Identification of an archaeal 2-hydroxy acid dehydrogenase catalyzing reactions involved in coenzyme biosynthesis in methanoarchaea
J. Bacteriol.
182
3688-3692
2000
Methanocaldococcus jannaschii (Q60176), Methanocaldococcus jannaschii, Methanocaldococcus jannaschii DSM 2661 (Q60176)
brenda
Madern, D.; Ebel, C.; Dale, H.A.; Lien, T.; Steen, I.H.; Birkeland, N.K.; Zaccai, G.
Differences in the oligomeric states of the LDH-like L-MalDH from the hyperthermophilic archaea Methanococcus jannaschii and Archaeoglobus fulgidus
Biochemistry
40
10310-10306
2001
Archaeoglobus fulgidus (O08349), Archaeoglobus fulgidus, Methanocaldococcus jannaschii (Q60176), Methanocaldococcus jannaschii, Methanocaldococcus jannaschii DSM 2661 (Q60176)
brenda
Lee, B.I.; Chang, C.; Cho, S.J.; Eom, S.H.; Kim, K.K.; Yu, Y.G.; Suh, S.W.
Crystal structure of the MJ0490 gene product of the hyperthermophilic archaebacterium Methanococcus jannaschii, a novel member of the lactate/malate family of dehydrogenases
J. Mol. Biol.
307
1351-1362
2001
Methanocaldococcus jannaschii (Q60176), Methanocaldococcus jannaschii, Methanocaldococcus jannaschii DSM 2661 (Q60176)
brenda
Madern, D.
The putative L-lactate dehydrogenase from Methanococcus jannaschii is an NADPH-dependent L-malate dehydrogenase
Mol. Microbiol.
37
1515-1520
2000
Methanocaldococcus jannaschii (Q60176), Methanocaldococcus jannaschii DSM 2661 (Q60176)
brenda
EXTERNAL LINKS (specific for EC-Number 1.1.1.375)
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