Any feedback?
Please rate this page
(enzyme.php)
(0/150)

BRENDA support

BRENDA Home
show all | hide all No of entries

Information on EC 1.1.1.37 - malate dehydrogenase and Organism(s) Haloarcula marismortui and UniProt Accession Q07841

for references in articles please use BRENDA:EC1.1.1.37
Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
EC Tree
     1 Oxidoreductases
         1.1 Acting on the CH-OH group of donors
             1.1.1 With NAD+ or NADP+ as acceptor
                1.1.1.37 malate dehydrogenase
IUBMB Comments
There are several forms of malate dehydrogenases that differ by their use of substrate and cofactors. This NAD+-dependent enzyme forms oxaloacetate and unlike EC 1.1.1.38, malate dehydrogenase (oxaloacetate-decarboxylating), is unable to convert it to pyruvate. Also oxidizes some other 2-hydroxydicarboxylic acids. cf. EC 1.1.1.82, malate dehydrogenase (NADP+); EC 1.1.1.299, malate dehydrogenase [NAD(P)+]; and EC 1.1.5.4, malate dehydrogenase (quinone).
Specify your search results
Select one or more organisms in this record: ?
This record set is specific for:
Haloarcula marismortui
UNIPROT: Q07841
Show additional data
Do not include text mining results
Include (text mining) results
Include results (AMENDA + additional results, but less precise)
Word Map
hide
The taxonomic range for the selected organisms is: Haloarcula marismortui
The enzyme appears in selected viruses and cellular organisms
Synonyms
malate dehydrogenase, mdh, mitochondrial malate dehydrogenase, malic dehydrogenase, cytosolic malate dehydrogenase, maldh, nad-dependent malate dehydrogenase, mitochondrial mdh, s-mdh, l-malate dehydrogenase, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
halophilic malate dehydrogenase
-
(R)-2-hydroxyacid dehydrogenase
-
-
-
-
L-malate dehydrogenase
-
-
-
-
L-malate:NAD oxidoreductase
-
-
malate (NAD) dehydrogenase
-
-
-
-
malate dehydrogenase (NAD)
-
-
-
-
malic acid dehydrogenase
-
-
-
-
malic dehydrogenase
-
-
-
-
mbNAD-MDH
-
-
-
-
mNAD-MDH
-
-
-
-
NAD+-dependent malate dehydrogenase
-
-
NAD-dependent malate dehydrogenase
-
-
-
-
NAD-dependent malic dehydrogenase
-
-
-
-
NAD-L-malate dehydrogenase
-
-
-
-
NAD-linked malate dehydrogenase
-
-
-
-
NAD-malate dehydrogenase
-
-
-
-
NAD-malic dehydrogenase
-
-
-
-
NAD-specific malate dehydrogenase
-
-
-
-
VEG69
-
-
-
-
Vegetative protein 69
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
oxidation
-
-
-
-
reduction
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
(S)-malate:NAD+ oxidoreductase
There are several forms of malate dehydrogenases that differ by their use of substrate and cofactors. This NAD+-dependent enzyme forms oxaloacetate and unlike EC 1.1.1.38, malate dehydrogenase (oxaloacetate-decarboxylating), is unable to convert it to pyruvate. Also oxidizes some other 2-hydroxydicarboxylic acids. cf. EC 1.1.1.82, malate dehydrogenase (NADP+); EC 1.1.1.299, malate dehydrogenase [NAD(P)+]; and EC 1.1.5.4, malate dehydrogenase (quinone).
CAS REGISTRY NUMBER
COMMENTARY hide
9001-64-3
-
SUBSTRATE
PRODUCT                       
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
-
-
-
r
oxaloacetate + NADH + H+
(S)-malate + NAD+
show the reaction diagram
pyruvate + NADH + H+
(S)-lactate + NAD+
show the reaction diagram
wild-type enzyme shows no activity with pyruvate. Mutant enzyme R100Q has considerably higher specificity for pyruvate than for oxaloacetate
-
-
?
(S)-malate + NAD+
oxaloacetate + NADH + H+
show the reaction diagram
-
-
-
-
r
malate + NAD+
oxaloacetate + NADH + H+
show the reaction diagram
-
-
-
-
r
oxaloacetate + NADH
L-malate + NAD+
show the reaction diagram
oxaloacetate + NADH + H+
(S)-malate + NAD+
show the reaction diagram
NATURAL SUBSTRATE
NATURAL PRODUCT
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
-
-
-
r
(S)-malate + NAD+
oxaloacetate + NADH + H+
show the reaction diagram
-
-
-
-
r
malate + NAD+
oxaloacetate + NADH + H+
show the reaction diagram
-
-
-
-
r
oxaloacetate + NADH + H+
(S)-malate + NAD+
show the reaction diagram
-
-
-
-
r
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
chloride
binding site structure analysis, structural adaptation in the halophilic protein, residue Lys205 is involved, the anion influences the oligomeric state of the enzyme, overview
NaCl
activation of the enzyme was obtained by increasing the salt concentration to 3 M NaCl
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
NADH
-
MDH activity is strongly inhibited by excess of oxaloacetate and NADH
oxaloacetate
-
MDH activity is strongly inhibited by excess of oxaloacetate and NADH
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
NaCl
-
activates at 3 M
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.012
NADH
pH 8.0, 25°C, recombinant wild-type enzyme and mutant K205A
0.13 - 29.4
oxaloacetate
2.2 - 2.9
pyruvate
0.024
NADH
-
60°C, pH 8.0
additional information
additional information
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.3 - 197
oxaloacetate
2.1 - 12.3
pyruvate
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0014 - 200
oxaloacetate
1 - 5.6
pyruvate
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
evolution
-
MDH is a ubiquitous enzyme found in prokaryotic and eukaryotic organisms. The enzyme belongs to the superfamily of 2-ketoacid NAD(P)+-dependent dehydrogenases. MDH has diverged into two distinct phylogenetic groups. One group includes cytoplasmic MDH, chloroplast MDH, and MDH from Thermus flavus; the other group includes MDHs that are similar to lactate dehydrogenase (LDH). Structure comparisons, the MDHs are mostly dimeric or tetrameric, overview
physiological function
-
regulation of MDH activity, overview
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
32638
x * 32638, calculated from sequence
33000
-
mass spectrometry
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
?
x * 32638, calculated from sequence
dimer
monomer
the monomer is in an inactive molten globule-like state, which can be reactivated through a structural change induced by NADH binding that allows it to associate into active dimers
tetramer
additional information
-
oligomeric states of MDHs, overview
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
sitting drop reverse vapour diffusion method, crystal structure of the R207S/R292S mutant of malate dehydrogenase is solved at 1.95 A
the structure of the mutant E267R apoenzyme is determined to 2.6 A resolution and the structure of the wild-type apoenzyme is determined to 2.9 A resolution
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
E243R
mutation does not affect enzyme activity. The mutant enzyme is more halophilic than the wild-type protein. It is more sensitive to temperature and requires significantly higher concentrations of NaCl or KCl for equivalent stability
E267R
the numbering is not equivalent to the numbering of UniProt. The E267R mutation points into a central ordered water cavity, disrupting protein-solvent interactions. The mutant enzyme requires higher concentrations of the solvent salt for stability similar to that of the wild type
K205A
site-directed mutagenesis, the oligomeric state of the mutant changes with the nature of the anion bound, the mutant is dimeric or tetrameric, overview
R100Q
the mutant enzyme has considerably higher specificity for pyruvate than for oxaloacetate. Whereas the Km value for pyruvate is increased about 2fold, that for oxaloacetate increases 30fold. The R100Q mutant is not subjected to substrate inhibition, at least not at substrate concentrations up to 30 mM, and the highest kcat value is obtained at the lowest salt concentration used (0.15 M NaCl)
R207S/R292S
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
8
-
Hm MalDH dissociates into dimers at 2 M NaCl, the dimer is as active as the wild type tetramer at pH 8, but loses its activity at pH 7
286675
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
45
30 min, 50% loss of activity, mutant enzyme R207S/R292S
63
t1/2 is 510 min for the wild-type enzyme and 15 min for mutant enzyme E243R
75
30 min, 50% loss of activity, wild-type enzyme
-10 - 35
-
at MgCl concentrations below 0.5 M or CaCl concentrations below 0.35 M, the stability of the protein increases with decreasing temperature down to -10°C. At higher concentrations (0.8-1.5 M MgCl2 or 0.5-1.0 M CaCl2), the curves are bell-shaped with symmetric decreases in stability around 4°C
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
in KCl at 25°C, 50% residual activity is observed after 24 h for mutant enzyme E243R in 2.3 M salt, compared to 1.3 M salt for wild-type enzyme. In KCl at 4°C, the mutant shows 50% stability in 1.1 M salt
at 10 mM MgCl2, residual activity after 24 h in H2O is less than 20% at 4°C, whereas in D2O the protein is stable with 100% residual activity
-
at 4°C, the protein at pH 7.0 is stable between 0.5 M and 0.9 M MgCl2. At pH 8.0, it is stable between 0.05 M and 1.2 M MgCl2
-
Ca2+, Mg2+, Li+, NH4+, Na+, K+, Rb+ and Cs+ stabilize the enzyme in order of decreasing efficiency
-
completely stable in absence of salt
-
fast dynamics of the enzyme is measured by neutron scattering under various solvent conditions influencing protein stability
-
only stable in highly concentrated solutions of certain salts
-
protein-solvent interactions modulate through different mechanisms protein stabilization at high salt
-
stability increases with increasing salt concentration, and when D2O replaces H2O. Below 10°C, it is stable in approximately 0.1 M NaCl/2H2O
-
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant enzyme
recombinant wild-type and mutant enzymes from Escherichia coli strain BL21(DE3) by gel filtration, hydrophobic interaction chromatography using 4 M KF and 1.3 M ammonium sulfate for elution, followed by dialysis
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
cloned with the Escherichia coli expression vector pET11a, large amounts of a soluble but inactive form of the enzyme are produced upon its induction
expression in Escherichia coli
expression of wild-type and mutant enzymes in Escherichia coli strain BL21(DE3)
overexpression in Escherichia coli
wild-type and E267R protein are overexpressed in Escherichia coli
expression in Escherichia coli
-
gene encoding the halophilic MalDH cloned into M13mp18 phage
-
structural gene expressed in Escherichia coli expression vector pET11a, large amounts of soluble but inactive form of the enzyme produced upon its induction
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
transcriptional regulation of mdh gene, overview
-
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Musrati, R.A.; Kollarova, M.; Mernik, N.; Mikulasova, D.
Malate dehydrogenase: Distribution, function and properties
Gen. Physiol. Biophys.
17
193-210
1998
Saccharomyces cerevisiae, Citrullus lanatus, Escherichia coli, Eucalyptus globulus, Euglena gracilis, Thermus thermophilus, Haloarcula marismortui, Methanothermus fervidus, Mus musculus, Nitzschia alba, Rattus norvegicus, Kitasatospora aureofaciens, Sulfolobus acidocaldarius, Sus scrofa, Zea mays
Manually annotated by BRENDA team
Madern, D.; Ebel, C.; Mevarech, M.; Richard, S.B.; Pfister, C.; Zaccai, G.
Insights into the molecular relationships between malate and lactate dehydrogenases: Structural and biochemical properties of monomeric and dimeric intermediates of a mutant of tetrameric L-[LDH-like] malate dehydrogenase from the halophilic archaeon Haloarcula marismortui
Biochemistry
39
1001-1010
2000
Haloarcula marismortui, Sus scrofa
Manually annotated by BRENDA team
Madern, D.; Zaccai, G.
Molecular adaptation: the malate dehydrogenase from the extreme halophilic bacterium Salinibacter ruber behaves like a non-halophilic protein
Biochimie
86
295-303
2004
Haloarcula marismortui, Salinibacter ruber
Manually annotated by BRENDA team
Madern, D.; Ebel, C.
Influence of an anion-binding site in the stabilization of halophilic malate dehydrogenase from Haloarcula marismortui
Biochimie
89
981-987
2007
Haloarcula marismortui (Q07841), Haloarcula marismortui
Manually annotated by BRENDA team
Cendrin, F.; Chroboczek, J.; Zaccai, G.; Eisenberg, H.; Mevarech, M.
Cloning, sequencing, and expression in Escherichia coli of the gene coding for malate dehydrogenase of the extremely halophilic archaebacterium Haloarcula marismortui
Biochemistry
32
4308-4313
1993
Haloarcula marismortui (Q07841), Haloarcula marismortui, Haloarcula marismortui DSM 3752 (Q07841)
Manually annotated by BRENDA team
Richard, S.B.; Madern, D.; Garcin, E.; Zaccai, G.
Halophilic adaptation: novel solvent protein interactions observed in the 2.9 and 2.6 A resolution structures of the wild type and a mutant of malate dehydrogenase from Haloarcula marismortui
Biochemistry
39
992-1000
2000
Haloarcula marismortui (Q07841), Haloarcula marismortui, Haloarcula marismortui DSM 3752 (Q07841)
Manually annotated by BRENDA team
Ebel, C.; Costenaro, L.; Pascu, M.; Faou, P.; Kernel, B.; Proust-De Martin, F.; Zaccai, G.
Solvent interactions of halophilic malate dehydrogenase
Biochemistry
41
13234-13244
2002
Haloarcula marismortui
Manually annotated by BRENDA team
Madern, D.; Pfister, C.; Zaccai, G.
Mutation at a single acidic amino acid enhances the halophilic behaviour of malate dehydrogenase from Haloarcula marismortui in physiological salts
Eur. J. Biochem.
230
1088-1095
1995
Haloarcula marismortui (Q07841), Haloarcula marismortui, Haloarcula marismortui DSM 3752 (Q07841)
Manually annotated by BRENDA team
Madern, D.; Zaccai, G.
Stabilisation of halophilic malate dehydrogenase from Haloarcula marismortui by divalent cations - effects of temperature, water isotope, cofactor and pH
Eur. J. Biochem.
249
607-611
1997
Haloarcula marismortui
Manually annotated by BRENDA team
Bonnete, F.; Madern, D.; Zaccai, G.
Stability against denaturation mechanisms in halophilic malate dehydrogenase "adapt" to solvent conditions
J. Mol. Biol.
244
436-447
1994
Haloarcula marismortui
Manually annotated by BRENDA team
Irimia, A.; Ebel, C.; Madern, D.; Richard, S.B.; Cosenza, L.W.; Zaccai, G.; Vellieux, F.M.
The oligomeric states of Haloarcula marismortui malate dehydrogenase are modulated by solvent components as shown by crystallographic and biochemical studies
J. Mol. Biol.
326
859-873
2003
Haloarcula marismortui (Q07841), Haloarcula marismortui, Haloarcula marismortui DSM 3752 (Q07841)
Manually annotated by BRENDA team
Tehei, M.; Madern, D.; Pfister, C.; Zaccai, G.
Fast dynamics of halophilic malate dehydrogenase and BSA measured by neutron scattering under various solvent conditions influencing protein stability
Proc. Natl. Acad. Sci. USA
98
14356-14361
2001
Haloarcula marismortui
Manually annotated by BRENDA team
Takahashi-Iniguez, T.; Aburto-Rodriguez, N.; Vilchis-Gonzalez, A.; Flores, M.
Function, kinetic properties, crystallization, and regulation of microbial malate dehydrogenase
J. Zhejiang Univ. Sci. B
17
247-261
2016
Aeropyrum pernix, Archaeoglobus fulgidus, Bacillus subtilis, uncultured bacterium, Corynebacterium glutamicum, Escherichia coli, Glaesserella parasuis, Haloarcula marismortui, Helicobacter pylori, Methanothermobacter thermautotrophicus, Methanocaldococcus jannaschii, Nitrosomonas europaea, Pseudomonas stutzeri, Kitasatospora aureofaciens, Streptomyces coelicolor, uncultured bacterium MPOB, Bacillus subtilis B1
-
Manually annotated by BRENDA team