Information on EC 1.1.1.39 - malate dehydrogenase (decarboxylating)

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The expected taxonomic range for this enzyme is: Eukaryota, Bacteria

EC NUMBER
COMMENTARY
1.1.1.39
-
RECOMMENDED NAME
GeneOntology No.
malate dehydrogenase (decarboxylating)
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
(S)-malate + NAD+ = pyruvate + CO2 + NADH
show the reaction diagram
sequential mechanism, each of the substrate pairs binds randomly to the enzyme
-
(S)-malate + NAD+ = pyruvate + CO2 + NADH
show the reaction diagram
sequential mechanism
Crassula argentea
-
(S)-malate + NAD+ = pyruvate + CO2 + NADH
show the reaction diagram
slow reaction transient in the form of a lag before reaching a steady-state rate in assay
Crassula argentea
-
(S)-malate + NAD+ = pyruvate + CO2 + NADH
show the reaction diagram
rapid equilibrium reaction of the intersecting type
-
(S)-malate + NAD+ = pyruvate + CO2 + NADH
show the reaction diagram
sequential mechanism with each substrate bound randomly
-
(S)-malate + NAD+ = pyruvate + CO2 + NADH
show the reaction diagram
-
-
-
-
(S)-malate + NAD+ = pyruvate + CO2 + NADH
show the reaction diagram
reaction mechanism of oxidative decarboxylation
-
(S)-malate + NAD+ = pyruvate + CO2 + NADH
show the reaction diagram
active site structure, catalytic residues are Y126, R181, K199, D295, N343, and N479
-
(S)-malate + NAD+ = pyruvate + CO2 + NADH
show the reaction diagram
reaction mechanism, active site structure, enzyme-cofactor interactions, overview
-
(S)-malate + NAD+ = pyruvate + CO2 + NADH
show the reaction diagram
catalytic mechanism, malate is bound deeply in the active site, Mn2+ catalyzes the entire reaction, Lys183 is the general base for oxidation, Tyr112-Lys183 functions as the general acid-base pair to catalyze the tautomerization of the enolpyruvate product from decarboxylation to pyruvate, substrate and cofacor binding modes
-
(S)-malate + NAD+ = pyruvate + CO2 + NADH
show the reaction diagram
acid-base chemical mechanism for Ascaris suum malic enzyme
-
(S)-malate + NAD+ = pyruvate + CO2 + NADH
show the reaction diagram
isozyme NAD-ME2 and chimeric mutant NAD-ME1q follow a sequential ordered Bi-Ter mechanism, NAD+ being the leading substrate followed by (S)-malate. Hetereodimer NAD-MEH can bind both substrates randomly. Interaction between NAD-ME1 and -ME2 generates a heteromeric isozyme NAD-MEH with a particular kinetic behaviour; isozyme NAD-ME2 and chimeric mutant NAD-ME1q follow a sequential ordered Bi-Ter mechanism, NAD+ being the leading substrate followed by (S)-malate. Isozyme NAD-ME1 and hetereodimer NAD-MEH can bind both substrates randomly. However, NAD-ME1 shows a preferred route that involves the addition of NAD+ first. interaction between NAD-ME1 and -ME2 generates a heteromeric isozyme NAD-MEH with a particular kinetic behaviour
-
REACTION TYPE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
oxidation
-
-
-
-
oxidative decarboxylation
-
-
-
-
redox reaction
-
-
-
-
reduction
-
-
-
-
PATHWAY
KEGG Link
MetaCyc Link
anaerobic energy metabolism (invertebrates, mitochondrial)
-
C4 photosynthetic carbon assimilation cycle, NAD-ME type
-
C4 photosynthetic carbon assimilation cycle, PEPCK type
-
Carbon fixation in photosynthetic organisms
-
chitin degradation to ethanol
-
gluconeogenesis I
-
Metabolic pathways
-
Microbial metabolism in diverse environments
-
Pyruvate metabolism
-
SYSTEMATIC NAME
IUBMB Comments
(S)-malate:NAD+ oxidoreductase (decarboxylating)
Does not decarboxylate added oxaloacetate.
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
AZC3656 protein
-
-
AZC3656 protein
B6E9W4
-
AZC3656 protein
Sinorhizobium sp. NGR234
B6E9W4
-
-
dehydrogenase, malate
-
-
-
-
diphosphate nucleotide dependent malic enzyme
-
-
DMA
-
-
-
-
DME
B6E9W4
-
DME
Sinorhizobium sp. NGR234
B6E9W4
-
-
m-NAD-ME
-
-
m-NAD-ME
-
-
malic enzyme
-
-
-
-
malic enzyme
-
-
malic enzyme
-
-
malic enzyme
-
-
malic enzyme
-
-
malic enzyme
Lactobacillus casei BL23 and ATCC 334
-
-
-
malic enzyme
-
-
malic enzyme
A4F2S6
-
malic enzyme
Rhodopseudomonas palustris No. 7
A4F2S6
-
-
malic enzyme 2
-
-
malic enzyme 2
-
-
malic enzyme-NAD
-
-
malic enzyme-NAD
Streptomyces coelicolor M145
-
-
-
ME
-
-
-
-
ME-NAD
Streptomyces coelicolor M145
-
-
-
mitochondrial malic enzyme
-
-
mitochondrial NAD(P)+-dependent malic enzyme
-
-
mitochondrial NAD+-dependent malic enzyme
-
-
mitochondrial NAD-malic enzyme
-
-
NAD(P)+-malic enzyme
-
-
NAD(P)+-malic enzyme
B6E9W4
-
NAD(P)+-malic enzyme
Sinorhizobium sp. NGR234
B6E9W4
-
-
NAD+-dependent malic enzyme
-
-
NAD-dependent malic enzyme
A9LIN4
-
NAD-dependent malic enzyme
Triticum aestivum Jinmai 47
A9LIN4
-
-
NAD-malic enzyme
-
-
-
-
NAD-malic enzyme
-
-
NAD-malic enzyme
Q8L7K9
-
NAD-malic enzyme
Q9SIU0
-
NAD-malic enzyme
Q9T0H6
-
NAD-malic enzyme
-
-
NAD-malic enzyme
-
-
NAD-malic enzyme
-
-
NAD-ME
-
-
-
-
NAD-ME
A9LIN4
-
NAD-ME
Triticum aestivum Jinmai 47
A9LIN4
-
-
NAD-ME1
Q9SIU0
-
NAD-MEH
Q8L7K9, Q9T0H6
-
NAD-preferring malic enzyme
-
-
NAD-preferring ME
-
-
NAD-specific malic enzyme
-
-
-
-
pyruvic-malic carboxylase
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
9028-46-0
-
ORGANISM
COMMENTARY
LITERATURE
SEQUENCE CODE
SEQUENCE DB
SOURCE
Amaranthus edulis
-
-
-
Manually annotated by BRENDA team
isozyme NAD-ME1
UniProt
Manually annotated by BRENDA team
isozyme NAD-ME1; isozyme NAD-ME1 encoded by gene AtNAD-ME1
UniProt
Manually annotated by BRENDA team
isozyme NAD-ME2
UniProt
Manually annotated by BRENDA team
isozyme NAD-ME2; isozyme NAD-ME2 encoded by gene AtNAD-ME2
UniProt
Manually annotated by BRENDA team
gene azc3656
-
-
Manually annotated by BRENDA team
var. botrytis
-
-
Manually annotated by BRENDA team
strain IFO 13182
-
-
Manually annotated by BRENDA team
Brevundimonas diminuta IFO 13182
strain IFO 13182
-
-
Manually annotated by BRENDA team
Crassula argentea
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
Heliocarpus sp.
-
-
-
Manually annotated by BRENDA team
gene maeE
-
-
Manually annotated by BRENDA team
Lactobacillus casei BL23 and ATCC 334
gene maeE
-
-
Manually annotated by BRENDA team
Mnium undulatum
-
-
-
Manually annotated by BRENDA team
Odontotermes sp.
-
-
-
Manually annotated by BRENDA team
isozyme ME2
-
-
Manually annotated by BRENDA team
Rhodopseudomonas palustris No. 7
-
UniProt
Manually annotated by BRENDA team
salmon
-
-
-
Manually annotated by BRENDA team
strain NGR234; gene azc3656 or dme
Uniprot
Manually annotated by BRENDA team
Sinorhizobium sp. NGR234
strain NGR234; gene azc3656 or dme
Uniprot
Manually annotated by BRENDA team
var. Chieftan
-
-
Manually annotated by BRENDA team
var. urgenta
-
-
Manually annotated by BRENDA team
gene Sco2951
-
-
Manually annotated by BRENDA team
Streptomyces coelicolor M145
gene Sco2951
-
-
Manually annotated by BRENDA team
hexaploid wheat
UniProt
Manually annotated by BRENDA team
Triticum aestivum Jinmai 47
hexaploid wheat
UniProt
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
malfunction
B6E9W4
dme mutants of the broad-host-range Sinorhizobium sp. strain NGR234 form nodules whose level of N2 fixation vary from 27 to 83% (plant dry weight) of the wild-type level, depending on the host plant inoculated. The single dme mutant fixes N2 at reduced rate. A pckA dme double mutant has no N2-fixing activity, PCK is phosphoenolpyruvate carboxykinase. Symbiotic phenotypes of NGR234 and NGR234 dme mutants on different host plants, overview
malfunction
-
the single Sco2951 and the double Sco2951 Sco5261 mutants, deficient in ME-NAD and ME-NADP, EC 1.1.1.40, activity, display a strong reduction in the production of the polyketide antibiotic actinorhodin. Additionally, the Sco2951/Sco5261 mutant shows a decrease in stored triacylglycerides during exponential growth
malfunction
Sinorhizobium sp. NGR234
-
dme mutants of the broad-host-range Sinorhizobium sp. strain NGR234 form nodules whose level of N2 fixation vary from 27 to 83% (plant dry weight) of the wild-type level, depending on the host plant inoculated. The single dme mutant fixes N2 at reduced rate. A pckA dme double mutant has no N2-fixing activity, PCK is phosphoenolpyruvate carboxykinase. Symbiotic phenotypes of NGR234 and NGR234 dme mutants on different host plants, overview
-
malfunction
Streptomyces coelicolor M145
-
the single Sco2951 and the double Sco2951 Sco5261 mutants, deficient in ME-NAD and ME-NADP, EC 1.1.1.40, activity, display a strong reduction in the production of the polyketide antibiotic actinorhodin. Additionally, the Sco2951/Sco5261 mutant shows a decrease in stored triacylglycerides during exponential growth
-
metabolism
-
the malic enzyme is involved in the (S)-malate catabolic pathways and the putative gluconeogenic pathways, overview
metabolism
-
the citrate-malate-pyruvate cycle serves to regenerate NAD+ and maintain glycolytic flux. Pyruvate cycles all lead to the exchange of reducing equivalents from mitochondrial NADH to cytosolic NADPH. Malic enzyme is integral to the coupling of metabolism with insulin secretion
physiological function
-
the malic enzyme pathway enables Lactobacillus casei to grow on L-malic acid., requirement of the MaeKR two-component system for L-malic acid utilization via a malic enzyme pathway, overview
physiological function
-
for a metabolic condition in which the mitochondrial NAD level is low and the (S)-malate level is high, the activity of homodimeric isozyme NAD-ME2 and/or heterodimer NAD-MEH would be preferred over that of homodimeric isozyme NAD-ME1; for a metabolic condition in which the mitochondrial NAD level is low and the (S)-malate level is high, the activity of homodimeric isozyme NAD-ME2 and/or heterodimer NAD-MEH would be preferred over that of homodimeric isozyme NAD-ME1
physiological function
A4F2S6
malic enzyme plays an important role in the metabolic regulation under photoheterotrophic conditions, carbon metabolic pathway, overview
physiological function
-
siRNA knockdown and isotopic labeling strategies to evaluate the role of cytosolic and mitochondrial isozymes of malic enzyme in facilitating malate-pyruvate cycling in the context of fuel-stimulated insulin secretion, overview
physiological function
-
DME is considered an important enzyme for regulating C4-dicarboxylic acid metabolism in N2-fixing bacteroids because its activity is strongly inhibited by acetyl-CoA and stimulated by fumarate and succinate. The NAD+-malic enzyme is required for N2 fixation, and this activity is thought to be required for the anaplerotic synthesis of pyruvate
physiological function
B6E9W4
AZC3656 protein is a NAD+-malic enzyme, i.e. DME, while AZC0119 protein is not a malic enzyme. DME is considered an important enzyme for regulating C4-dicarboxylic acid metabolism in N2-fixing bacteroids because its activity is strongly inhibited by acetyl-CoA and stimulated by fumarate and succinate. The NAD+-malic enzyme is required for N2 fixation, and this activity is thought to be required for the anaplerotic synthesis of pyruvate. But NGR234 bacteroids appear to synthesize pyruvate from TCA cycle intermediates via DME or PCK, phosphoenolpyruvate carboxykinase, pathways, overview
physiological function
-
the enzyme plays a role in antibiotic and triacylglycerol production, e.g. production of the polyketide antibiotic actinorhodin, overview
physiological function
Lactobacillus casei BL23 and ATCC 334
-
the malic enzyme pathway enables Lactobacillus casei to grow on L-malic acid., requirement of the MaeKR two-component system for L-malic acid utilization via a malic enzyme pathway, overview
-
physiological function
Rhodopseudomonas palustris No. 7
-
malic enzyme plays an important role in the metabolic regulation under photoheterotrophic conditions, carbon metabolic pathway, overview
-
physiological function
Sinorhizobium sp. NGR234
-
AZC3656 protein is a NAD+-malic enzyme, i.e. DME, while AZC0119 protein is not a malic enzyme. DME is considered an important enzyme for regulating C4-dicarboxylic acid metabolism in N2-fixing bacteroids because its activity is strongly inhibited by acetyl-CoA and stimulated by fumarate and succinate. The NAD+-malic enzyme is required for N2 fixation, and this activity is thought to be required for the anaplerotic synthesis of pyruvate. But NGR234 bacteroids appear to synthesize pyruvate from TCA cycle intermediates via DME or PCK, phosphoenolpyruvate carboxykinase, pathways, overview
-
physiological function
Streptomyces coelicolor M145
-
the enzyme plays a role in antibiotic and triacylglycerol production, e.g. production of the polyketide antibiotic actinorhodin, overview
-
metabolism
Lactobacillus casei BL23 and ATCC 334
-
the malic enzyme is involved in the (S)-malate catabolic pathways and the putative gluconeogenic pathways, overview
-
additional information
-
deletion of either the gene encoding the histidine kinase or the response regulator of the TC system results in the loss of the ability to grow on L-malic acid, thus indicating that the cognate TC system regulates and is essential for the expression of malic enzyme. Expression of maeE is induced in the presence of L-malic acid and repressed by glucose, whereas TC system expression is induced by L-malic acid and is not repressed by glucose
additional information
-
interaction between NAD-ME1 and -ME2 generates a heteromeric enzyme NAD-MEH with a particular kinetic behaviour. The N-terminal region of NAD-ME1 and -ME2 is associated with the order of substrate binding. The chimeric enzyme NAD-ME1q, that is composed of the first 176 amino acid residues of NAD-ME2 and the central and C-terminal sequence of NAD-ME1, shows a hyperbolic behaviour for (S)-malate and NAD+. Product-inhibition pattern of NAD-ME1q with the three products supports a sequential ordered mechanism; interaction between NAD-ME1 and -ME2 generates a heteromeric enzyme NAD-MEH with a particular kinetic behaviour. The N-terminal region of NAD-ME1 and -ME2 is associated with the order of substrate binding. The chimeric enzyme NAD-ME1q, that is composed of the first 176 amino acid residues of NAD-ME2 and the central and C-terminal sequence of NAD-ME1, shows a hyperbolic behaviour for (S)-malate and NAD+. Product-inhibition pattern of NAD-ME1q with the three products supports a sequential ordered mechanism
additional information
A4F2S6
enzyme activity is allosterically regulated by acetyl-CoA
additional information
-
identification of specific domains of the primary structure, which are involved in the differential allosteric regulation. Different properties of NAD-ME1, -2, and -H, mitochondrial NAD-ME activity may be regulated by varying native association in vivo, rendering enzymatic entities with distinct allosteric regulation to fulfill specific roles, overview; identification of specific domains of the primary structure, which are involved in the differential allosteric regulation. Different properties of NAD-ME1, -2, and -H, mitochondrial NAD-ME activity may be regulated by varying native association in vivo, rendering enzymatic entities with distinct allosteric regulation to fulfill specific roles, overview; identification of specific domains of the primary structure, which are involved in the differential allosteric regulation. Different properties of NAD-ME1, -2, and -H, mitochondrial NAD-ME activity may be regulated by varying native association in vivo, rendering enzymatic entities with distinct allosteric regulation to fulfill specific roles, overview
additional information
-
higher expression of ME2 correlates with the degree of cell de-differentiation. Knockdown of ME2 leads to induction of erythroid differentiation, and diminished proliferation of tumor cells and increased apoptosis in vitro. ME2 knockdown also totally abolishes growth of K562 cells in nude mice. Depletion of endogenous ME2 levels enhances reactive oxygen species, increases NAD+/NADH and NADP+/NADPH ratio and inhibits ATP production in K562 cells. ME2 depletion resulted in high orotate levels, suggesting potential impairment of pyrimidine metabolism
additional information
Lactobacillus casei BL23 and ATCC 334
-
deletion of either the gene encoding the histidine kinase or the response regulator of the TC system results in the loss of the ability to grow on L-malic acid, thus indicating that the cognate TC system regulates and is essential for the expression of malic enzyme. Expression of maeE is induced in the presence of L-malic acid and repressed by glucose, whereas TC system expression is induced by L-malic acid and is not repressed by glucose
-
additional information
Rhodopseudomonas palustris No. 7
-
enzyme activity is allosterically regulated by acetyl-CoA
-
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
(2R,3R)-erythrofluoromalate + NAD+
?
show the reaction diagram
-
-
-
-
?
(2S,3R)-tartrate + NAD+
?
show the reaction diagram
-
-
-
-
?
(S)-malate + NAD(P)+
pyruvate + CO2 + NAD(P)H
show the reaction diagram
-
-
-
-
r
(S)-malate + NAD(P)+
pyruvate + CO2 + NAD(P)H
show the reaction diagram
-
-
-
-
?
(S)-malate + NAD+
pyruvate + CO2 + NADH
show the reaction diagram
-
-
-
-
r
(S)-malate + NAD+
pyruvate + CO2 + NADH
show the reaction diagram
-
-
-
-
r
(S)-malate + NAD+
pyruvate + CO2 + NADH
show the reaction diagram
-
-
-
-
r
(S)-malate + NAD+
pyruvate + CO2 + NADH
show the reaction diagram
-
-
-
-
?
(S)-malate + NAD+
pyruvate + CO2 + NADH
show the reaction diagram
-
-
-
-
r
(S)-malate + NAD+
pyruvate + CO2 + NADH
show the reaction diagram
-
-
-
-
?
(S)-malate + NAD+
pyruvate + CO2 + NADH
show the reaction diagram
-
-
-
-
?
(S)-malate + NAD+
pyruvate + CO2 + NADH
show the reaction diagram
-
-
-
-
r
(S)-malate + NAD+
pyruvate + CO2 + NADH
show the reaction diagram
-
-
-
-
r
(S)-malate + NAD+
pyruvate + CO2 + NADH
show the reaction diagram
Q8L7K9, Q9SIU0
-
-
-
r
(S)-malate + NAD+
pyruvate + CO2 + NADH
show the reaction diagram
A9LIN4
-
-
-
?
(S)-malate + NAD+
pyruvate + CO2 + NADH
show the reaction diagram
B6E9W4
-
-
-
?
(S)-malate + NAD+
pyruvate + CO2 + NADH
show the reaction diagram
-
enzyme is involved in carbon fixation and metabolism, regulation of the pathways, overview
-
-
?
(S)-malate + NAD+
pyruvate + CO2 + NADH
show the reaction diagram
-
mitochondrial isozyme ME2 responds to elevated amino acids and serves to supply sufficient pyruvate for increased Krebs cycle flux when glucose is limiting
-
-
r
(S)-malate + NAD+
pyruvate + CO2 + NADH
show the reaction diagram
Q8L7K9, Q9SIU0
the enzyme plays a central role in the metabolite flux through the tricarboxylic acid cycle, overview
-
-
r
(S)-malate + NAD+
pyruvate + CO2 + NADH
show the reaction diagram
-
the enzyme plays a role in symbiotic N2 fixation, overview
-
-
r
(S)-malate + NAD+
pyruvate + CO2 + NADH
show the reaction diagram
-
the mitochondrial NAD-malic enzyme catalyzes the oxidative decarboxylation of malate to pyruvate and CO2
-
-
r
(S)-malate + NAD+
pyruvate + CO2 + NADH
show the reaction diagram
-
the NAD-malic enzyme catalyzes the oxidative decarboxylation of (S)-malate via oxaloacetate, Arg181 is within hydrogen bonding distance of the 1-carboxylate of malate in the active site of the enzyme and interacts with the carboxamide side chain of the nicotinamide ring of NADH, but not with NAD+
-
-
r
(S)-malate + NAD+
pyruvate + CO2 + NADH
show the reaction diagram
-
the decarboxylation reaction is preferred, overview
-
-
r
(S)-malate + NAD+
pyruvate + CO2 + NADH
show the reaction diagram
Brevundimonas diminuta IFO 13182
-
-
-
-
r
(S)-malate + NAD+
pyruvate + CO2 + NADH
show the reaction diagram
Triticum aestivum Jinmai 47
A9LIN4
-
-
-
?
(S)-malate + NAD+
pyruvate + CO2 + NADH
show the reaction diagram
Streptomyces coelicolor M145
-
-
-
-
?
(S)-malate + NAD+
pyruvate + CO2 + NADH
show the reaction diagram
Sinorhizobium sp. NGR234
B6E9W4
-
-
-
?
(S)-malate + NAD+
pyruvate + NADH + CO2
show the reaction diagram
-
-
-
-
ir
(S)-malate + NAD+
?
show the reaction diagram
-
-
-
-
-
(S)-malate + NAD+
?
show the reaction diagram
-
the enzyme plays a special role in the decarboxylation of C4 acids to pyruvate and CO2, which are used in subsequent photosynthesis. pH, NAD+, and coenzyme A levels in the matrix act together to regulate (S)-malate oxidation
-
-
?
(S)-malate + NAD+
pyruvate + NADH + H+ + CO2
show the reaction diagram
-
-
-
-
?
(S)-malate + NAD+
pyruvate + NADH + H+ + CO2
show the reaction diagram
-
-
-
-
ir
(S)-malate + NAD+
pyruvate + NADH + H+ + CO2
show the reaction diagram
-
-
-
-
?
(S)-malate + NAD+
pyruvate + NADH + H+ + CO2
show the reaction diagram
-
-
-
-
r
(S)-malate + NAD+
pyruvate + NADH + H+ + CO2
show the reaction diagram
A4F2S6
-
-
-
?
(S)-malate + NAD+
pyruvate + NADH + H+ + CO2
show the reaction diagram
-, Q8L7K9, Q9T0H6
NAD-ME1, -ME2 and -MEH catalyse the reverse reaction of pyruvate reductive carboxylation with very low catalytic activity, supporting the notion that these isoforms act only in (S)-malate oxidation in plant mitochondria
-
-
r
(S)-malate + NAD+
pyruvate + NADH + H+ + CO2
show the reaction diagram
-, Q8L7K9, Q9T0H6
NAD-ME1, -ME2 and -MEH catalyse the reverse reaction of pyruvate reductive carboxylation with very low catalytic activity, supporting the notion that these isoforms act only in (S)-malate oxidation in plant mitochondria
-
-
ir
(S)-malate + NAD+
pyruvate + NADH + H+ + CO2
show the reaction diagram
-
very low activity in the reverse reaction in vitro
-
-
r
(S)-malate + NAD+
pyruvate + NADH + H+ + CO2
show the reaction diagram
Lactobacillus casei BL23 and ATCC 334
-
-
-
-
?
(S)-malate + NAD+
pyruvate + NADH + H+ + CO2
show the reaction diagram
Rhodopseudomonas palustris No. 7
A4F2S6
-
-
-
?
(S)-malate + NADP+
pyruvate + CO2 + NADPH
show the reaction diagram
-
-
-
ir
(S)-malate + NADP+
pyruvate + CO2 + NADPH
show the reaction diagram
-
-
-
?
(S)-malate + NADP+
pyruvate + CO2 + NADPH
show the reaction diagram
-
-
-
r
(S)-malate + NADP+
pyruvate + CO2 + NADPH
show the reaction diagram
-
-
-
?
(S)-malate + NADP+
pyruvate + CO2 + NADPH
show the reaction diagram
B6E9W4
-
-
-
?
(S)-malate + NADP+
pyruvate + CO2 + NADPH
show the reaction diagram
-
at 1.5% of the activity with NAD+
-
?
(S)-malate + NADP+
pyruvate + CO2 + NADPH
show the reaction diagram
-
15% of the activity with NAD+
-
?
(S)-malate + NADP+
pyruvate + CO2 + NADPH
show the reaction diagram
Crassula argentea
-
14% of the activity with NAD+
-
?
(S)-malate + NADP+
pyruvate + CO2 + NADPH
show the reaction diagram
Sinorhizobium sp. NGR234
B6E9W4
-
-
-
?
(S)-malate + NADP+
pyruvate + NADPH + H+ + CO2
show the reaction diagram
Rhodopseudomonas palustris, Rhodopseudomonas palustris No. 7
A4F2S6
NADP+ shows 22% of the activity with NAD+
-
-
?
L-aspartate + NAD+
iminopyruvate + CO2 + NADH
show the reaction diagram
-
-
-
-
?
L-malate + NAD+
pyruvate + NADH + H+ + CO2
show the reaction diagram
-
-
-
-
r
malate + NAD+
pyruvate + CO2 + NADH
show the reaction diagram
-
-
-
ir
malate + NAD+
pyruvate + CO2 + NADH
show the reaction diagram
-
-
-
?
malate + NAD+
pyruvate + CO2 + NADH
show the reaction diagram
-
-
-
ir
malate + NAD+
pyruvate + CO2 + NADH
show the reaction diagram
-
-
-
?
malate + NAD+
pyruvate + CO2 + NADH
show the reaction diagram
-
-
-
?
malate + NAD+
pyruvate + CO2 + NADH
show the reaction diagram
-
-
-
?
malate + NAD+
pyruvate + CO2 + NADH
show the reaction diagram
-
-
-
?
malate + NAD+
pyruvate + CO2 + NADH
show the reaction diagram
-
-
-
?
malate + NAD+
pyruvate + CO2 + NADH
show the reaction diagram
-
-
-
?
malate + NAD+
pyruvate + CO2 + NADH
show the reaction diagram
-
-
-
r
malate + NAD+
pyruvate + CO2 + NADH
show the reaction diagram
-
-
-
-
malate + NAD+
pyruvate + CO2 + NADH
show the reaction diagram
-
-
-
?
malate + NAD+
pyruvate + CO2 + NADH
show the reaction diagram
-
-
-
?
malate + NAD+
pyruvate + CO2 + NADH
show the reaction diagram
salmon
-
-
-
?
malate + NAD+
pyruvate + CO2 + NADH
show the reaction diagram
-
-
-
?
malate + NAD+
pyruvate + CO2 + NADH
show the reaction diagram
Crassula argentea
-
-
-
?
malate + NAD+
pyruvate + CO2 + NADH
show the reaction diagram
Crassula argentea
-
-
-
?
malate + NAD+
pyruvate + CO2 + NADH
show the reaction diagram
Crassula argentea
-
-
-
?
malate + NAD+
pyruvate + CO2 + NADH
show the reaction diagram
Crassula argentea
-
-
-
?
malate + NAD+
pyruvate + CO2 + NADH
show the reaction diagram
-
-
-
?
malate + NAD+
pyruvate + CO2 + NADH
show the reaction diagram
-
-
-
?
malate + NAD+
pyruvate + CO2 + NADH
show the reaction diagram
-
-
-
?
malate + NAD+
pyruvate + CO2 + NADH
show the reaction diagram
-
-
-
-
malate + NAD+
pyruvate + CO2 + NADH
show the reaction diagram
-
-
-
?
malate + NAD+
pyruvate + CO2 + NADH
show the reaction diagram
-
-
-
?
malate + NAD+
pyruvate + CO2 + NADH
show the reaction diagram
-
-
-
?
malate + NAD+
pyruvate + CO2 + NADH
show the reaction diagram
-
-
-
ir
malate + NAD+
pyruvate + CO2 + NADH
show the reaction diagram
-
-
-
-
malate + NAD+
pyruvate + CO2 + NADH
show the reaction diagram
Amaranthus edulis
-
-
-
?
malate + NAD+
pyruvate + CO2 + NADH
show the reaction diagram
-
-
-
?
malate + NAD+
pyruvate + CO2 + NADH
show the reaction diagram
Crassula argentea
-
activity of the reverse reaction is 1.5% of that of the forward reaction
-
r
malate + NAD+
pyruvate + CO2 + NADH
show the reaction diagram
-
ionized malic acid is the true substrate
-
?
malate + NAD+
pyruvate + CO2 + NADH
show the reaction diagram
-
no decarboxylation of malate in absence of either Mg2+ or NAD+
-
?
pyruvate + CO2 + NADH
(S)-malate + NAD+
show the reaction diagram
Crassula argentea
-
activity is 1.5% of the decarboxylation of (S)-malate
-
r
pyruvate + NAD+ + HCO3-
(S)-malate + NADH
show the reaction diagram
Brevundimonas diminuta, Brevundimonas diminuta IFO 13182
-
method optimization of the reverse reaction of the malic enzyme for HCO3- fixation into pyruvic acid to produce L-malic acid with NADH generation including the activity of glucose-6-phosphate dehydrogenase, EC 1.1.1.49, from Leuconostoc mesenteroides
-
-
?
meso-tartrate + NAD+
?
show the reaction diagram
-
-
-
-
?
additional information
?
-
-
no decarboxylation of oxaloacetate
-
-
-
additional information
?
-
-
no decarboxylation of oxaloacetate
-
-
-
additional information
?
-
-
no decarboxylation of oxaloacetate
-
-
-
additional information
?
-
-
the Ascaris suum enzyme forms complexes with the structurally similar human enzyme
-
-
-
additional information
?
-
-
enzyme shows a strict requirement for 2S-stereochemistry
-
-
-
additional information
?
-
-
comparison of enzyme activity in different species under different conditions, significant differences in the accumulation of malate between day and night, overview
-
-
-
additional information
?
-
-
NAD-ME1 does not perform decarboxylation of oxaloacetate, NAD-ME2 does not perform decarboxylation of oxaloacetate, NAD-MEH does not perform decarboxylation of oxaloacetate
-
-
-
additional information
?
-
Rhodopseudomonas palustris, Rhodopseudomonas palustris No. 7
A4F2S6
the enzyme shows 1% of the forward reaction activity in the reverse reaction and in decarboxylation oxaloacetate. D-malate and succinate are poor substrates showing 3.9% and 8.2% of the activity with (S)-malate
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
(S)-malate + NAD(P)+
pyruvate + CO2 + NAD(P)H
show the reaction diagram
-
-
-
-
r
(S)-malate + NAD(P)+
pyruvate + CO2 + NAD(P)H
show the reaction diagram
-
-
-
-
?
(S)-malate + NAD+
pyruvate + CO2 + NADH
show the reaction diagram
-
-
-
-
r
(S)-malate + NAD+
pyruvate + CO2 + NADH
show the reaction diagram
-
-
-
-
r
(S)-malate + NAD+
pyruvate + CO2 + NADH
show the reaction diagram
-
-
-
-
?
(S)-malate + NAD+
pyruvate + CO2 + NADH
show the reaction diagram
-
-
-
-
r
(S)-malate + NAD+
pyruvate + CO2 + NADH
show the reaction diagram
-
-
-
-
r
(S)-malate + NAD+
pyruvate + CO2 + NADH
show the reaction diagram
A9LIN4
-
-
-
?
(S)-malate + NAD+
pyruvate + CO2 + NADH
show the reaction diagram
B6E9W4
-
-
-
?
(S)-malate + NAD+
pyruvate + CO2 + NADH
show the reaction diagram
-
enzyme is involved in carbon fixation and metabolism, regulation of the pathways, overview
-
-
?
(S)-malate + NAD+
pyruvate + CO2 + NADH
show the reaction diagram
-
mitochondrial isozyme ME2 responds to elevated amino acids and serves to supply sufficient pyruvate for increased Krebs cycle flux when glucose is limiting
-
-
r
(S)-malate + NAD+
pyruvate + CO2 + NADH
show the reaction diagram
Q8L7K9, Q9SIU0
the enzyme plays a central role in the metabolite flux through the tricarboxylic acid cycle, overview
-
-
r
(S)-malate + NAD+
pyruvate + CO2 + NADH
show the reaction diagram
-
the enzyme plays a role in symbiotic N2 fixation, overview
-
-
r
(S)-malate + NAD+
pyruvate + NADH + CO2
show the reaction diagram
-
-
-
-
ir
(S)-malate + NAD+
?
show the reaction diagram
-
the enzyme plays a special role in the decarboxylation of C4 acids to pyruvate and CO2, which are used in subsequent photosynthesis. pH, NAD+, and coenzyme A levels in the matrix act together to regulate (S)-malate oxidation
-
-
?
(S)-malate + NAD+
pyruvate + NADH + H+ + CO2
show the reaction diagram
-
-
-
-
?
(S)-malate + NAD+
pyruvate + NADH + H+ + CO2
show the reaction diagram
-
-
-
-
ir
(S)-malate + NAD+
pyruvate + NADH + H+ + CO2
show the reaction diagram
-
-
-
-
?
(S)-malate + NAD+
pyruvate + NADH + H+ + CO2
show the reaction diagram
-
-
-
-
r
(S)-malate + NAD+
pyruvate + NADH + H+ + CO2
show the reaction diagram
A4F2S6
-
-
-
?
(S)-malate + NAD+
pyruvate + NADH + H+ + CO2
show the reaction diagram
-, Q8L7K9, Q9T0H6
NAD-ME1, -ME2 and -MEH catalyse the reverse reaction of pyruvate reductive carboxylation with very low catalytic activity, supporting the notion that these isoforms act only in (S)-malate oxidation in plant mitochondria
-
-
r
(S)-malate + NAD+
pyruvate + NADH + H+ + CO2
show the reaction diagram
-, Q8L7K9, Q9T0H6
NAD-ME1, -ME2 and -MEH catalyse the reverse reaction of pyruvate reductive carboxylation with very low catalytic activity, supporting the notion that these isoforms act only in (S)-malate oxidation in plant mitochondria
-
-
ir
(S)-malate + NAD+
pyruvate + NADH + H+ + CO2
show the reaction diagram
Lactobacillus casei BL23 and ATCC 334
-
-
-
-
?
(S)-malate + NAD+
pyruvate + CO2 + NADH
show the reaction diagram
Brevundimonas diminuta IFO 13182
-
-
-
-
r
(S)-malate + NAD+
pyruvate + CO2 + NADH
show the reaction diagram
Triticum aestivum Jinmai 47
A9LIN4
-
-
-
?
(S)-malate + NAD+
pyruvate + NADH + H+ + CO2
show the reaction diagram
Rhodopseudomonas palustris No. 7
A4F2S6
-
-
-
?
(S)-malate + NAD+
pyruvate + CO2 + NADH
show the reaction diagram
Streptomyces coelicolor M145
-
-
-
-
?
(S)-malate + NAD+
pyruvate + CO2 + NADH
show the reaction diagram
Sinorhizobium sp. NGR234
B6E9W4
-
-
-
?
(S)-malate + NADP+
pyruvate + CO2 + NADPH
show the reaction diagram
B6E9W4
-
-
-
?
(S)-malate + NADP+
pyruvate + NADPH + H+ + CO2
show the reaction diagram
Rhodopseudomonas palustris, Rhodopseudomonas palustris No. 7
A4F2S6
NADP+ shows 22% of the activity with NAD+
-
-
?
(S)-malate + NADP+
pyruvate + CO2 + NADPH
show the reaction diagram
Sinorhizobium sp. NGR234
B6E9W4
-
-
-
?
L-malate + NAD+
pyruvate + NADH + H+ + CO2
show the reaction diagram
-
-
-
-
r
additional information
?
-
-
the Ascaris suum enzyme forms complexes with the structurally similar human enzyme
-
-
-
additional information
?
-
-
comparison of enzyme activity in different species under different conditions, significant differences in the accumulation of malate between day and night, overview
-
-
-
COFACTOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
NAD+
Crassula argentea
-
cofactor
NAD+
Amaranthus edulis
-
cofactor
NAD+
-
cofactor
NAD+
-
binding site structure
NAD+
-
conformational change upon binding
NAD+
-
binding structure, overview
NAD+
A4F2S6
preferred cofactor
NAD+
-
preferred cofactor
NAD+
-
dependent on
NAD+
-
His362 is involved in NAD+-specific catalysis of NAD-ME, and residue 314 may interact with the bisphosphate of the NAD+ moiety, structure analysis, overview
NADH
Q8L7K9, Q9SIU0
;
NADP+
Crassula argentea
-
14% of the activity with NAD+; cofactor
NADP+
-
at 1.5% of the activity with NAD+
NADP+
-
15% of the activity with NAD+
NADP+
-
activity is maximal 65% of the activity with NAD+
NADP+
-
activity with NADP+ is about twice that measured with NAD+
additional information
-
binding site structure of NADH
-
additional information
-
Arg181 is within hydrogen bonding distance of the 1-carboxylate of malate in the active site of the enzyme and interacts with the carboxamide side chain of the nicotinamide ring of NADH, but not with NAD+
-
additional information
A4F2S6
the enzyme uses both NAD+ and NADP+
-
METALS and IONS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
Co2+
-
can replace Mg2+ in activation. Km: 0.018 mM
Co2+
A4F2S6
activates 7fold at 1-10 mM
Mg2+
-
no decarboxylation of malate in absence of either Mg2+ or NAD+. Km: 0.04 mM
Mg2+
Crassula argentea
-
uses Mg2+ or Mn2+ as the required divalent cation
Mg2+
Crassula argentea
-
activation by Mg2+ or Mn2+
Mg2+
-
activation by Mg2+ or Mn2+
Mg2+
-
completely dependent on the presence of Mg2+ or Mn2+
Mg2+
-
no activation by Mg2+
Mg2+
-
Km with NAD+: 4.25 mM, Km with NADP+: 13.3 mM; Mn2+ or Mg2+ required
Mg2+
-
bivalent metal ion required, Mn2+ is more effective than Mg2+
Mg2+
-
activation by Mn2+, at 1 mM, is 10% and 20% higher than activation with 1 mM Mg2+ in the presence of NAD+ and NADP+; completely dependent on the presence of Mg2+ or Mn2+
Mg2+
-
divalent metal ion required, NAD+-linked activity shows maximal activity at 5 mM Mg2+
Mg2+
-
preferably used as metal cofactor
Mg2+
-
strict requirement for a divalent cation, maximal activation at 2 mM
Mg2+
-
required
Mg2+
A4F2S6
activates 12fold at 1 mM and 15fold at 10 mM
Mg2+
-
activates
Mg2+
-
activates
Mn2+
-
can replace Mg2+ in activation
Mn2+
Crassula argentea
-
divalent cation required, Mg2+ or Mn2+
Mn2+
Crassula argentea
-
activation by Mn2+ or Mg2+
Mn2+
-
activation by Mn2+ or Mg2+
Mn2+
-
completely dependent on the presence of Mg2+ or Mn2+
Mn2+
-
absolute requirement for Mn2+, no activation by Mg2+
Mn2+
-
Km with NAD+: 0.14 mM, Km with NADP+: 0.81 mM; Mn2+ or Mg2+ required
Mn2+
-
bivalent metal ion required, Mn2+ is more effective than Mg2+
Mn2+
-
completely dependent on the presence of Mg2+ or Mn2+
Mn2+
-
strict requirement for a divalent cation, maximal activation at 5 mM
Mn2+
-
required
Mn2+
-
reversible structural interconversion to the Lu3+-binding form, metal binding site structure
Mn2+
-
required
Mn2+
-
activates mutant N434A
Mn2+
-
during the catalytic process of malic enzyme, binding of metal ion induces a conformational change within the enzyme from the open form to an intermediate form, which upon binding of L-malate, transforms further into a catalytically competent closed form
Mn2+
-
activates; activates probably
Mn2+
A4F2S6
activates 13fold at 1 mM and 15fold at 10 mM
Mn2+
-
activates; activates; activates
NH4+
-
partially rescues the activity of the R181Q mutant by binding in the pocket vacated by the guanidinium group of R181, 2 mol of ammonia bind per mole of active sites, high-affinity Km is 0.7 mM, low-affinity Km is 420 mM
NH4+
A4F2S6
activates 12fold at 1 mM and 20fold at 10 mM
Ni2+
-
divalent metal ion required, NADP+-linked activity exhibits a maximum at 5 mM Ni2+
Zn2+
A4F2S6
5fold activation at 5 mM, only slight activation at 10 mM
Mn2+
-
activates, Km 0.08 mM in the decarboxylation/oxidation reaction
additional information
-
the reaction is dependent on divalent metal ions
additional information
A4F2S6
malic enzyme activity is markedly enhanced by mono- and divalent cations
INHIBITORS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
(S)-malate
-
above 10 mM
(S)-malate
-
isozyme NAD-ME2, competitive
5'-AMP
-
isozyme NAD-ME2, competitive versus NAD+, mixed inhibition versus (S)-malate
acetyl-CoA
-
potent inhibitor
acetyl-CoA
A4F2S6
enzyme activity is allosterically regulated by acetyl-CoA, almost complete inhibition at 0.05 mM
acetyl-CoA
B6E9W4
-
ATP
-
competitive with respect to (S)-malate
bicarbonate
Amaranthus edulis, Atriplex spongiosa
-
-
Bromopyruvate
-
-
Ca2+
A4F2S6
inhibits 30% at 1 mM and 60% at 10 mM
citrate
Crassula argentea
-
competitive
Cl-
Crassula argentea
-
-
CO2
-
chimeric mutant NAD-ME1q, mixed inhibition versus NAD+ and (S)-malate; isozyme NAD-ME2 and chimeric mutant NAD-ME1q, mixed inhibition versus NAD+ and (S)-malate
EDTA
A4F2S6
complete inhibition at 0.1 mM
fructose 6-phosphate
A4F2S6
competitive versus (S)-malate, 70% inhibition at 2.5 mM
L-aspartate
-
slightly competitive to malate, only slight inhibition below pH 6.0
Li+
A4F2S6
slight inhibition
Lu3+
-
strong inhibition, reversible slow-binding mechanism, reversible structural interconversion to the Mn2+-binding form, metal binding site structure
Na+
A4F2S6
complete inhibition at 10 mM, no effect by Na+ at 1 mM
NADH
Crassula argentea
-
product inhibition
NADH
-
isozyme NAD-ME2, competitive versus NAD+, mixed inhibition versus (S)-malate. NADH shows competitive and mixed-type inhibition versus NAD+ and (S)-malate with chimeric mutant NAD-ME1q; NADH shows competitive and mixed-type inhibition versus NAD+ and (S)-malate with chimeric mutant NAD-ME1q
oxalate
-
very tight binding inhibitor of the NAD-malic enzyme
oxaloacetate
A4F2S6
competitive versus (S)-malate, 20% inhibition at 2.5 mM
phosphoenolpyruvate
-
-
phosphoenolpyruvate
Crassula argentea
-
activates at low concentrations, deactivation at high concentrations
phosphoenolpyruvate
-
-
pyruvate
Crassula argentea
-
product inhibition
pyruvate
-
isozyme NAD-ME2, uncompetitive versus NAD+, mixed inhibition versus (S)-malate. Pyruvate inhibition is uncompetitive with respect to NAD+ and mixed with respect to (S)-malate for the chimeric mutant NAD-ME1q; pyruvate inhibition is uncompetitive with respect to NAD+ and mixed with respect to (S)-malate for the chimeric mutant NAD-ME1q
Tartrate
-
substrate analogue, isozyme NAD-ME2, uncompetitive versus NAD+, competitive versus (S)-malate
Tartronate
-
binding site structure at the active site, competitive
Urea
-
denaturation, in 3-5 M urea, the enzyme undergoes a reversible tetramer-dimer-monomer quaternary structural change in an acidic pH environment, which resulted in a molten globule state that is prone to aggregate, Mn2+ protects, overview
Mn2+
-
inhibits the reductive carboxylation reaction, inhibitory effect is about 20fold reduced by binding of fumarate and L-malate
additional information
-
water stress reduces the enzyme activity in vivo
-
additional information
-
product inhibition patterns of isozyme NAD-ME2, overview; product inhibition patterns of isozyme NAD-ME2, overview
-
additional information
-
keeping plants in CO2-free air suppresses the activities of NAD-ME
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
1-N6-etheno-CoA
Crassula argentea
-
activates
2-oxoglutarate
-
-
adenosine 5'-diphosphoglucose
-
activates
ADP
-
slight stimulstion
alpha-D-glucose 1-phosphate
-
activation
AMP
Crassula argentea
-
competitive activation
aspartate
-
stimulates
ATP
-
slight stimulstion
CoA
-
activation kinetics, overview; activation kinetics, overview
coenzyme A
-
serves to broaden the pH-optimum, at pH 7.5 approximately 4fold stimulation, the effect is more marked when HCO3 is also present, below pH 7 no effect on activity
coenzyme A
Crassula argentea
-
activates
coenzyme A
-
increases activity
D-fructose 1,6-biphosphate
-
-
-
D-fructose 6-phosphate
-
activation
D-glucose 6-phosphate
-
activation
fructose 1,6-bisphosphate
-
stimulates
fructose 1,6-bisphosphate
Crassula argentea
-
activates
fructose 1,6-bisphosphate
-
activates
fumarate
-
stimulates
fumarate
Crassula argentea
-
fumarate2- is a strong activator
fumarate
-
activates in both reaction directions synergistically with L-malate both binding at separate allosteric sites different from the active site, R105 and K143 are involved
fumarate
-
allosteric activator
fumarate
B6E9W4
-
gamma-amino-n-butyrate
-
slight activation
hydroxy-n-butyrate
-
slight activation
Hydroxypyruvate
-
slight activation
phosphoenolpyruvate
Crassula argentea
-
activates at low concentrations, decativation at high concentrations
phosphoenolpyruvate
-
-
SO42-
-
activates
succinate
-
stimulates
succinate
-
stimulates
succinate
B6E9W4
-
uridine 5'-diphosphoglucose
-
activates
L-Malate
-
activates in both reaction directions synergistically with fumarate both binding at separate allosteric sites different from the active site, R105 and K143 are involved
additional information
-
no activation by CoA and acetyl-CoA, poor activation by ATP and AMP; no activation by oxaloacetate, poor activation by ATP and AMP; poor activation by ATP and AMP
-
KM VALUE [mM]
KM VALUE [mM] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
2
-
(2R,3R)-erythrofluoromalate
-
25C
60
-
(2S)-aspartate
-
25C
1
-
(2S)-malate
-
25C
20
-
(2S,3R)-tartrate
-
25C, pH 7.8
0.1
-
(S)-malate
-
with NAD+ as cofactor
0.16
-
(S)-malate
-
pH 7.5, 25C
0.458
-
(S)-malate
-
with NADP+ as cofactor
0.5
-
(S)-malate
-
pH 7.0, 25C, mutant N434A, in presence of Mn2+
0.52
-
(S)-malate
-
-
0.53
-
(S)-malate
-
pH 8.5, 25C, recombinant wild-type enzyme
0.59
-
(S)-malate
Crassula argentea
-
activation by Mn2+
0.59
-
(S)-malate
B6E9W4
pH 7.8, 30C, AZC3656, in presence of 1 mM fumarate
0.64
-
(S)-malate
B6E9W4
pH 7.8, 30C, AZC3656, in presence of 10 mM succinate
0.76
-
(S)-malate
-
with NAD+ and Mn2+
0.8
-
(S)-malate
Crassula argentea
-
activation by Mn2+
0.8
-
(S)-malate
-
pH 7.0, 25C, wild-type enzyme
1.3
-
(S)-malate
-
pH 7.0, 25C, mutant S433A
1.7
-
(S)-malate
-
pH 7.0, 25C, mutant N479S
1.7
-
(S)-malate
A4F2S6
pH 7.2, 30C, with NAD+
1.8
-
(S)-malate
-
pH 7.0, 25C, mutant N479Q
2
3
(S)-malate
-
pH 8.5, 25C, recombinant mutant R181Q in presence of 60 mM guanidinium
2.2
-
(S)-malate
-
pH 7.0, 25C, mutant N434M
2.5
-
(S)-malate
-
-
2.6
-
(S)-malate
-
isozyme NAD-ME2, pH 6.5, temperature not specified in the publication
2.7
-
(S)-malate
-
pH 6.5, temperature not specified in the publication, NAD-MEH
2.7
-
(S)-malate
B6E9W4
pH 7.8, 30C, AZC3656
3
-
(S)-malate
Q8L7K9, Q9SIU0
pH 7.4, 30C, isozyme NAD-ME1; pH 7.4, 30C, isozyme NAD-ME2
3
-
(S)-malate
-
pH 6.4, temperature not specified in the publication, NAD-ME1; pH 6.6, temperature not specified in the publication, NAD-ME2
3.2
-
(S)-malate
-
with NAD+ as coenzyme, activation by Mn2+
4.2
-
(S)-malate
-
with NADP+ and Mn2+
4.3
-
(S)-malate
-
pH 7.0, 25C, mutant N434Q
5.97
-
(S)-malate
-
with NAD+ as coenzyme
6.03
-
(S)-malate
Crassula argentea
-
activation by Mg2+
8
-
(S)-malate
-
pH 8.5, 25C, recombinant mutant R181Q, in presence of 60 mM NH4+
8.1
-
(S)-malate
-
pH 8.0, 30C, recombinant enzyme
8.34
-
(S)-malate
-
with NADP+ as coenzyme
9.8
-
(S)-malate
-
with NADP+ as coenzyme, activation by Mn2+
12.3
-
(S)-malate
-
with NADP+ and Mg2+
12.54
-
(S)-malate
-
-
13
-
(S)-malate
-
with NAD+ as coenzyme, activation by Mg2+
14
-
(S)-malate
-
with NAD+ and Mg2+
15
-
(S)-malate
A4F2S6
pH 7.2, 30C, with NADP+
22.5
-
(S)-malate
-
with NADP+ as coenzyme, activation by Mg2+
27.6
-
(S)-malate
B6E9W4
pH 7.8, 30C, AZC3656, in presence of 0.05 mM acetyl-CoA
50
-
(S)-malate
-
pH 8.5, 25C, recombinant mutant R181Q
57
-
(S)-malate
-
pH 8.5, 25C, recombinant mutant R181K
13.48
-
CO2
Crassula argentea
-
activation by Mg2+
16.8
-
CO2
-
pH 7.0, 25C
0.035
-
NAD+
-
pH 8.5, 25C, recombinant wild-type enzyme
0.07
-
NAD+
-
pH 8.5, 25C, recombinant mutant R181Q
0.1
-
NAD+
-
activation by Mn2+
0.101
-
NAD+
B6E9W4
pH 7.8, 30C, AZC3656
0.11
-
NAD+
A4F2S6
pH 7.2, 30C, with (S)-malate
0.2
-
NAD+
-
pH 7.5, 25C
0.47
-
NAD+
-
with 30 mM Mg2+
0.48
-
NAD+
-
with 8 mM Mg2+
0.5
-
NAD+
-
with 80 mM Mg2+
0.5
-
NAD+
-
activation by Mn2+
0.5
-
NAD+
Q8L7K9, Q9SIU0
pH 7.4, 30C, isozyme NAD-ME1; pH 7.4, 30C, isozyme NAD-ME2
0.5
-
NAD+
-
pH 6.4, temperature not specified in the publication, NAD-ME1; pH 6.6, temperature not specified in the publication, NAD-ME2
0.55
-
NAD+
-
pH 6.5, temperature not specified in the publication, NAD-MEH
0.77
-
NAD+
Crassula argentea
-
activation by Mg2+
0.8
-
NAD+
-
pH 7.0, 25C, wild-type enzyme
0.82
-
NAD+
-
activation by Mg2+
0.9
-
NAD+
-
activation by Mg2+
1.1
-
NAD+
-
isozyme NAD-ME2, pH 6.5, temperature not specified in the publication
1.6
-
NAD+
-
pH 7.0, 25C, mutant S433A
1.7
-
NAD+
-
pH 7.0, 25C, mutant N479S
1.8
-
NAD+
-
pH 7.0, 25C, mutant N479Q
2
-
NAD+
-
pH 7.0, 25C, mutant N434A, in presence of Mn2+
3
-
NAD+
-
pH 7.0, 25C, mutant N434M
4.3
-
NAD+
-
pH 8.0, 30C, recombinant enzyme
5
-
NAD+
-
pH 7.0, 25C, mutant N434Q
0.06
-
NADH
-
pH 7.0, 25C
0.12
-
NADH
Crassula argentea
-
activation by Mn2+
0.207
-
NADP+
-
-
0.3
-
NADP+
-
activation by Mn2+
1.32
-
NADP+
-
activation by Mn2+
1.7
-
NADP+
-
with NADP+ as coenzyme
1.8
-
NADP+
A4F2S6
pH 7.2, 30C, with (S)-malate
2.1
-
NADP+
B6E9W4
pH 7.8, 30C, AZC3656
6.12
-
NADP+
-
activation by Mg2+
4.1
-
pyruvate
-
pH 7.0, 25C
15.03
-
pyruvate
Crassula argentea
-
activation by Mn2+
40
-
meso-tartrate
-
25C, pH 7.8
additional information
-
additional information
Crassula argentea
-
-
-
additional information
-
additional information
-
-
-
additional information
-
additional information
-
kinetics
-
additional information
-
additional information
-
detailed kinetic mechanism study, steady-state kinetics
-
additional information
-
additional information
-
kinetics of wild-type and mutant enzymes, primary deuterium and 13C isotope effects of mutant R181Q in the absence and presence of ammonium ions, overview
-
additional information
-
additional information
-
primary deuterium and 13C kinetic isotope effects, kinetics, and kinetic mechanism of wild-type and mutant enzymes, overview
-
additional information
-
additional information
-
kinetic mechanisms of homodimers NAD-ME1 and NAD-ME2, and of NAD-ME heterodimer NAD-MEH, overview. The first 176 amino acids are associated with the differences observed in the kinetic mechanisms of the enzymes. Activity of NAD-ME1 in the direction of malate decarboxylation shows a hyperbolic response, proposed kinetic model for NAD-ME1. Isozyme NAD-ME2 follows a sequential ordered Bi-Ter mechanism. Kinetic properties and mechanism of chimeric mutant NAD-ME1q, overview; kinetic mechanisms of homodimers NAD-ME1 and NAD-ME2, and of NAD-ME heterodimer NAD-MEH, overview. The first 176 amino acids are associated with the differences observed in the kinetic mechanisms of the enzymes. Activity of NAD-ME1 in the direction of malate decarboxylation shows a hyperbolic response, proposed kinetic model for NAD-ME1. Kinetic properties and mechanism of chimeric mutant NAD-ME1q, overview
-
additional information
-
additional information
A4F2S6
steady-state kinetics, overview
-
additional information
-
additional information
-
kinetic analysis and comparison of the different isozymes MAD-ME1, NAD-ME2, and NAD-MEH, and of mutants NADME1q and NAD-ME2q, overview; kinetic analysis and comparison of the different isozymes MAD-ME1, NAD-ME2, and NAD-MEH, and of mutants NADME1q and NAD-ME2q, overview; kinetic analysis and comparison of the different isozymes MAD-ME1, NAD-ME2, and NAD-MEH, and of mutants NADME1q and NAD-ME2q, overview
-
additional information
-
additional information
-
kinetics analysis of isozymes ME2 and ME3
-
TURNOVER NUMBER [1/s]
TURNOVER NUMBER MAXIMUM[1/s]
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
31.1
-
(S)-malate
Q8L7K9, Q9SIU0
pH 7.4, 30C, isozyme NAD-ME1
31.1
-
(S)-malate
-
pH 6.4, temperature not specified in the publication, NAD-ME1
39
-
(S)-malate
-
pH 6.5, temperature not specified in the publication, NAD-MEH
44.1
-
(S)-malate
Q8L7K9, Q9SIU0
pH 7.4, 30C, isozyme NAD-ME2
44.1
-
(S)-malate
-
pH 6.6, temperature not specified in the publication, NAD-ME2
46
-
(S)-malate
-
isozyme NAD-ME2, pH 6.5, temperature not specified in the publication
480
-
(S)-malate
A4F2S6
pH 7.2, 30C, with NADP+
617
-
(S)-malate
-
-
770
-
(S)-malate
A4F2S6
pH 7.2, 30C, with NAD+
31.1
-
NAD+
-
pH 6.4, temperature not specified in the publication, NAD-ME1
39
-
NAD+
-
pH 6.5, temperature not specified in the publication, NAD-MEH
44.1
-
NAD+
-
pH 6.6, temperature not specified in the publication, NAD-ME2
46
-
NAD+
-
isozyme NAD-ME2, pH 6.5, temperature not specified in the publication
720
-
NAD+
A4F2S6
pH 7.2, 30C, with (S)-malate
520
-
NADP+
A4F2S6
pH 7.2, 30C, with (S)-malate
kcat/KM VALUE [1/mMs-1]
kcat/KM VALUE [1/mMs-1] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
10.3
-
(S)-malate
-
pH 6.4, temperature not specified in the publication, NAD-ME1
466
14.2
-
(S)-malate
-
pH 6.5, temperature not specified in the publication, NAD-MEH
466
14.7
-
(S)-malate
-
pH 6.6, temperature not specified in the publication, NAD-ME2
466
3100
-
(S)-malate
A4F2S6
pH 7.2, 30C, with NAD+
466
3300
-
(S)-malate
A4F2S6
pH 7.2, 30C, with NADP+
466
60.2
-
NAD+
-
pH 6.4, temperature not specified in the publication, NAD-ME1
14330
67
-
NAD+
-
pH 6.5, temperature not specified in the publication, NAD-MEH
14330
88.2
-
NAD+
-
pH 6.6, temperature not specified in the publication, NAD-ME2
14330
6900
-
NAD+
A4F2S6
pH 7.2, 30C, with (S)-malate
14330
2900
-
NADP+
A4F2S6
pH 7.2, 30C, with (S)-malate
27497
Ki VALUE [mM]
Ki VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.45
-
5'-AMP
-
versus NAD+, pH 6.5, temperature not specified in the publication, isozyme NAD-ME2
1.5
-
5'-AMP
-
versus (S)-malate, pH 6.5, temperature not specified in the publication, isozyme NAD-ME2
3
-
CO2
-
versus NAD+, pH 6.5, temperature not specified in the publication, isozyme NAD-ME2
7
-
CO2
-
versus (S)-malate, pH 6.5, temperature not specified in the publication, isozyme NAD-ME2
7.4
-
fructose 6-phosphate
A4F2S6
pH 7.2, 30C, versus (S)-malate
58
-
L-aspartate
-
pH 8.4, 25C, versus malate
80
-
L-aspartate
-
pH 7.0, 25C, versus malate
0.0048
-
Lu3+
-
isomerized enzyme form, pH 7.4, 30C
0.041
-
NADH
-
versus (S)-malate, pH 6.5, temperature not specified in the publication, isozyme NAD-ME2
0.15
-
NADH
-
versus NAD+, pH 6.5, temperature not specified in the publication, isozyme NAD-ME2
0.006
-
oxalate
-
pH 7.0, 25C, recombinant wild-type enzyme
0.36
-
oxaloacetate
A4F2S6
pH 7.2, 30C, versus (S)-malate
11
-
pyruvate
-
versus NAD+, pH 6.5, temperature not specified in the publication, isozyme NAD-ME2
14
-
pyruvate
-
versus (S)-malate, pH 6.5, temperature not specified in the publication, isozyme NAD-ME2
0.8
-
Tartrate
-
versus (S)-malate, pH 6.5, temperature not specified in the publication, isozyme NAD-ME2
4
-
Tartrate
-
versus NAD+, pH 6.5, temperature not specified in the publication, isozyme NAD-ME2
0.148
-
Lu3+
-
native enzyme form, pH 7.4, 30C
additional information
-
additional information
-
inhibition kinetics
-
additional information
-
additional information
-
-
-
additional information
-
additional information
-
inhibition kinetics
-
additional information
-
additional information
-
inhibition patterns by measuring the initial rate as a function of malate or NAD+ with NAD+ or malate maintained equal to its Km at different fixed concentrations of oxalate, including zero, Ki, 2Ki, and 4Ki at pH 7.0 and 30 mM free Mg2+
-
SPECIFIC ACTIVITY [µmol/min/mg]
SPECIFIC ACTIVITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
0.017
-
-
water stress plants at daytime or at nighttime
0.036
-
-
control plants at daytime
0.107
-
-
control plants at nighttime
0.201
-
B6E9W4
NAD+-dependent ME activity in the wild-type strain, pH 7.8, 30C, AZC3656
0.989
-
-
purified native enzyme, reverse reaction
2.74
-
-
NAD+-linked activity
4.25
-
-
purified native enzyme, pH 7.0, 25C, carboxylation reaction
5.45
-
-
NADP+-linked activity
35.4
-
Crassula argentea
-
-
36.09
-
-
purified native enzyme, pH 7.5, 25C, decarboxylation reaction
64
-
A4F2S6
purified enzyme, pH 7.2, 30C
81.5
-
Crassula argentea
-
-
additional information
-
-
design of an assay procedure to minimize the influence of (S)-malate dehydrogenase and other factors
additional information
-
-
-
additional information
-
-
-
additional information
-
-
isozyme expression levels, pyruvate cycling and isozyme activity in pancreatic islets, overview
additional information
-
-
changes in NADH contents in the leaves of plant species towards the end of the light or darkness periods, diurnal changes in malate and citrate contents in gametophores kept under control, hypoxia, high irradiance, drought stress, and CO2-free air conditions, comparison to other species, overiew
pH OPTIMUM
pH MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
6
-
-
reverse reaction
6.4
-
-
activity with NADP+ and Mg2+
6.4
-
Q8L7K9, Q9SIU0
-
6.4
-
-
NAD-ME1
6.5
-
-
activity with NADP+ and Mn2+
6.5
-
-
forward reaction, assay at; forward reaction, assay at
6.5
-
-
NAD-MEH
6.6
-
Q8L7K9, Q9SIU0
-
6.6
-
-
NAD-ME2
6.7
-
-
enzyme complexed to Mg2+ and NAD+
6.8
-
-
activity with NAD+
6.9
-
-
activity with NADP+; with NAD+, without activator
7
-
-
catalytically competent enzyme-substrate complex formed upon binding malate
7
-
-
assay at
7
-
-
carboxylation reaction
7.1
-
Crassula argentea
-
activated by Mg2+
7.2
-
-
with NAD+ plus CoA
7.3
-
-
assay at
7.4
-
-
assay at
7.4
-
-
assay at
7.46
-
Crassula argentea
-
activated by Mn2+
7.5
-
A9LIN4
assay at
7.5
-
-
decarboxylation reaction
7.8
-
B6E9W4
AZC3656 shows high NAD+-ME activity at pH 7.8, with Michaelis-Menten-like kinetics, at various concentrations of malate, The enzyme exhibits only a very limited positive cooperativity with respect to malate
8.5
-
-
assay at, oxidation reaction
additional information
-
-
pH-dependency of the reaction kinetics, overview
pH RANGE
pH RANGE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
5.8
7.6
-
pH 5.8: about 60% of maximal activity, pH 7.6: about 40% of maximal activity
6
7.5
-
carboxylation reaction, activity range
6
8
-
decarboxylation reaction, activity range
6
8.5
-
about 40% of maximal activity at pH 6.0 and at pH 8.5
7
8.7
-
pH 7.0: about 30% of maximal activity, pH 8.7: about 45% of maximal activity
additional information
-
-
enzyme conformation at different pH values, overview
TEMPERATURE OPTIMUM
TEMPERATURE OPTIMUM MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
25
-
-
assay at
25
-
-
assay at, oxidation reaction
25
-
-
assay at
25
-
-
assay at
30
-
-
assay at
30
-
-
assay at
30
-
-
assay at, reverse reaction
30
-
B6E9W4
assay at
37
-
-
assay at
TEMPERATURE RANGE
TEMPERATURE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
30
60
-
30C: about 35% of maximal activity, 60C: about 50% of maximal activity
pI VALUE
pI VALUE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
6.3
-
A4F2S6
sequence calculation
SOURCE TISSUE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
SOURCE
-
the level of the enzyme in wild-type bacteroids is not limiting for N2-fixation
Manually annotated by BRENDA team
-
; NAD-ME1and -2 subunits show a distinct patterns of accumulation in the separate components of the floral organ; NAD-ME1and -2 subunits show a distinct patterns of accumulation in the separate components of the floral organ
Manually annotated by BRENDA team
-
insulinoma cells, isozyme ME2
Manually annotated by BRENDA team
-
erythroleukemia cells
Manually annotated by BRENDA team
Crassula argentea
-
-
Manually annotated by BRENDA team
-
bundle sheath
Manually annotated by BRENDA team
Q8L7K9, Q9SIU0
leaf crude extracts contain about 20% higher NAD-ME specific activities at the end of the night period than at the end of the day period, isozyme NAD-ME1 is more abundant during the night period; leaf crude extracts contain about 20% higher NAD-ME specific activities at the end of the night period than at the end of the day period, isozyme NAD-ME2 is more abundant during the night period
Manually annotated by BRENDA team
-
NAD-MEH and NADME1 act in concert in this tissue; the NAD-ME1 subunit is present at a slightly higher proportion than the NAD-ME2 subunit, and thus, NAD-MEH and NADME1 act in concert in this tissue; the NAD-ME1 subunit is present at a slightly higher proportion than the NAD-ME2 subunit, and thus, NAD-MEH and NADME1 act in concert in this tissue
Manually annotated by BRENDA team
-
high exnzyme activity
Manually annotated by BRENDA team
Triticum aestivum Jinmai 47
-
-
-
Manually annotated by BRENDA team
additional information
Q8L7K9, Q9SIU0
tissue specific expression of the isozyme, overview; tissue specific expression of the isozyme, overview
Manually annotated by BRENDA team
MOLECULAR WEIGHT
MOLECULAR WEIGHT MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
117500
-
Q8L7K9, Q9SIU0
gel filtration, isozyme NAD-ME2
119000
-
Crassula argentea
-
dimer, disc gel electrophoresis
120000
-
Crassula argentea
-
dimer, non-denaturing PAGE
120000
-
-
non-denaturing PAGE
120000
-
Q8L7K9, Q9SIU0
gel filtration, isozyme NAD-ME1
125000
-
-
NAD-MEH, gel filtration
170000
-
-
dimer, gel filtration
200000
-
-
sucrose density gradient centrifugation
230000
-
Crassula argentea
-
tetramer, non-denaturing PAGE
231000
-
Crassula argentea
-
tetramer, disc gel electrophoresis
270000
-
-
gel filtration
270000
-
-
gel filtration
279000
-
-
tetramer, gel filtration
300000
-
-
gel filtration
308000
-
-
gel filtration
350000
-
Crassula argentea
-
non-denaturing PAGE
388000
-
-
gel filtration
400000
-
-
octamer, gel filtration
490000
-
Crassula argentea
-
octamer, non-denaturing PAGE
490000
-
-
octamer, gel filtration, enzyme in octameric aggregation state
490000
-
-
gel filtration in presence of 5 mM dithiothreitol and 2 mM MgCl2
491000
-
Crassula argentea
-
tetramer, disc gel electrophoresis
680000
-
-
gel filtration
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
?
Crassula argentea
-
x * 55000, alpha, + x * 61000, beta, SDS-PAGE
?
-
x * 82000, SDS-PAGE
decamer
-
10 * 64000, SDS-PAGE
dimer
-
1 * 61000 + 1 * 64000, SDS-PAGE
dimer
Q8L7K9, Q9SIU0
2 * 58000, beta-subunit, isozyme NAD-ME2, SDS-PAGE; 2 * 65000, alpha-subunit, isozyme NAD-ME1, SDS-PAGE
octamer
-
alpha4beta4, 4 * 61000 + 4 * 58000, SDS-PAGE
oligomer
A4F2S6
x * 86000
oligomer
Rhodopseudomonas palustris No. 7
-
x * 86000
-
tetramer
-
4 * 85000, SDS-PAGE
tetramer
-
dimer of dimers
tetramer
-
structure analysis from crystal structure, the enzyme is a tetrameric protein with double dimer quaternary structure, pH dependence of enzyme structure, overview
tetramer
-
4 * 61000, SDS-PAGE
dimer
-
isozymes NAD-ME1 and NAD-ME2 assemble as homo- and heterodimers, the latter is termed NAD-MEH, in vitro and in vivo. Interaction between NAD-ME1 and -ME2 generates a heteromeric enzyme NAD-MEH with a particular kinetic behaviour; isozymes NAD-ME1 and NAD-ME2 assemble as homo- and heterodimers, the latter is termed NAD-MEH, in vitro and in vivo. Interaction between NAD-ME1 and -ME2 generates a heteromeric enzyme NAD-MEH with a particular kinetic behaviour
additional information
Crassula argentea
-
the enzyme exists in at least three aggregational states: dimer, tetramer and octamer
additional information
Q8L7K9, Q9SIU0
the isozyme NAD-ME1 is grouped into the clade that includes enzymes with alpha-subunits with molecular masses of approximately 65 kDa in the plant NAD-ME phylogenetic tree, isozymes NAD-ME1 and NAD-ME2 form both homo- and heterooligomers in vitro and in vivo, overview; the isozyme NAD-ME2 is grouped into the clades with enzymes possessing beta-subunits with molecular masses of approximately 58 kD in the plant NAD-ME phylogenetic tree, isozymes NAD-ME1 and NAD-ME2 form both homo- and heterooligomers in vitro and in vivo, overview
additional information
-
isozyme NAD-ME1 primary structure and domain analysis, overview; isozyme NAD-ME2 primary structure and domain analysis, overview; isozyme NAD-MEH primary structure and domain analysis, overview
Crystallization/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
enzyme in binary complex with NAD+, by hanging drop vapour diffusion method, from solution containing 5 mM NAD+, 10 mM tartronate, and 20 mM MgSO4, for cryoprotection soaking overnight in 100 mM Tris-HCl, pH 7.5, with 25% PEG w/v 15 mM NAD+, 10 mM 2-mercaptoethanol, and glycerol up to a final concentration of 20% v/v, X-ray diffraction structure determination and analysis at 2.3 A resolution, structure modeling
-
quarternary complex of purified enzyme with NADH, tartronate, and Mg2+, hanging drop vapour diffusion method, from 100 mM Tris-SO4, pH 7.3, 100 mM sodium acetate, 15% PEG 4000, 5 mM NADH, 10 mM tartronate, 20 mM MgSO4, 10 mM 2-mercaptoethanol, and 0.02% sodium azide, for cryoprotection the crystals are soaked in 25% PEG 4000, 15 mM NAD+, 10 mM 2-mercaptoethanol, and 100 mM Tris-SO4, pH 7.5, for 2 h, then 24 h in the crystallization buffer plus 20% EG v/v, X-ray diffraction structure determination and analysis at 2.0 A resolution, structure modeling
-
enzyme complexed with the natural substrate malate or pyruvate, NAD+ or NADH, Mn2+, and the allosteric activator fumarate, X-ray diffraction structure determination and analysis at 2.1 A resolution, structure modeling
-
pH STABILITY
pH STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
7
9
-
25C, 5 min, stable
8
-
A4F2S6
purified enzyme, most stable at
TEMPERATURE STABILITY
TEMPERATURE STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
30
-
A4F2S6
purified enzyme, stable up to, loss of activity above
45
-
-
15 min, stable at or below
55
-
-
15 min, complete inactivation
70
-
A4F2S6
purified enzyme, almost complete inactivation
GENERAL STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
freezing of crude enzyme extract treated on Sephadex G-25 destroys activity
-
photooxidation with methylene blue
-
OXIDATION STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
photooxidation with methylene blue
-
286701
STORAGE STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
crude and partially purified enzyme retains activity for several months when stored as a protein suspension in 75% saturated (NH4)2SO4 solution
-
-80C, purified native enzyme, 8 months, completely stable
A4F2S6
-20C, stable for several weeks
-
4C, loss of activity upon prolonged storage
-
Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
recombinant His-tagged NAD-ME1 and mutants NADME1q and NAD-ME2q from Escherichia coli strain BL21(DE3) by nickel affinity chromatography and gel filtration; recombinant His-tagged NAD-ME2 and mutants NADME1q and NAD-ME2q from Escherichia coli strain BL21(DE3) by nickel affinity chromatography and gel filteration; recombinant His-tagged NAD-MEH from Escherichia coli strain BL21(DE3) by nickel affinity chromatography and gel filtration
-
recombinant NAD-ME1, NAD-ME2, and NAD-MEH; recombinant NAD-ME1, NAD-ME2, and NAD-MEH
-
several steps
-
native enzyme 44fold
-
native enzyme 84.7fold by anion exchange and affinity chromatography, and gel filtration
-
-
Crassula argentea
-
native enzyme partially by preparation of mitochondria, method, overview
-
native enzyme 1500fold to homogeneity by ammonium sulfate fractionation, anion exchange and hydrophobic interaction chromatography, adsorption chromatography, ultrafiltration, and gel filtration
A4F2S6
recombinant His-tagged enzyme AZC3656 from Escherichia coli by nickel affinity chromatography
B6E9W4
Cloned/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
expression of His-tagged NAD-ME1 and of mutants NADME1q and NAD-ME2q in Escherichia coli strain BL21(DE3); expression of His-tagged NAD-ME2 and mutants NADME1q and NAD-ME2q in Escherichia coli strain BL21(DE3); expression of His-tagged NAD-MEH in Escherichia coli strain BL21(DE3)
-
gene AtNAD-ME1, DNA and amino acid sequence determination and analysis, phylogenetic tree; gene AtNAD-ME2, DNA and amino acid sequence determination and analysis, phylogenetic tree
Q8L7K9, Q9SIU0
recombinant expression of NAD-ME1, NAD-ME2, and NAD-MEH; recombinant expression of NAD-ME1, NAD-ME2, and NAD-MEH
-
expression of mutant enzymes in Escherichia coli strain M15
-
gene maeE, is encoded in a cluster consisting of two diverging operons, maePE and maeKR, DNA and amino acid sequence determination and analysis, phylogenetic analysis
-
isozyme expression analysis, overview
-
ME2, quantitative real time PCR expression analysis
-
DNA and amino acid sequence determination and analysis, expression in Escherichia coli strain JM109
A4F2S6
gene dme or azc3656, DNA and amino acid sequence determination and analysis, expression as His-tagged enzyme in Escherichia coli
B6E9W4
gene Sco2951, DNA and amino acid sequence determination and analysis, phylogenetic analysis, recombinant expressionin Escherichia coli strain BL21(DE3)
-
DNA and amino acid sequence determination and analysis
A9LIN4
EXPRESSION
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
expression of maeE is repressed by glucose
-
expression of maeE is induced in the presence of L-malic acid. MaeR binds specifically to a set of direct repeats [5'-TTATT(A/T)AA-3'] in the mae promoter region and activates the expression of the diverging operons maePE and maeKR
-
expression of maeE is repressed by glucose
Lactobacillus casei BL23 and ATCC 334
-
-
expression of maeE is induced in the presence of L-malic acid. MaeR binds specifically to a set of direct repeats [5'-TTATT(A/T)AA-3'] in the mae promoter region and activates the expression of the diverging operons maePE and maeKR
Lactobacillus casei BL23 and ATCC 334
-
-
no enzyme expression in darkness. Abscisic acid, salicylic acid, and PEG treatments completely abolish enzyme expression,
A9LIN4
no enzyme expression in darkness. Abscisic acid, salicylic acid, and PEG treatments completely abolish enzyme expression,
Triticum aestivum Jinmai 47
-
-
ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
K143A
-
site-directed mutagenesis, malate binding residue, mutant shows highly increased kcat for malate and fumarate compared to the wild-type enzyme
K362H
-
the mutant enzyme displays a considerable elevation in Km for NADP+, and the kcat for NAD+ value is elevated compared to the wild-type enzyme
N434A
-
site-directed mutagenesis, the interaction of the 434 position residue with malate is lost in the mutant, causing malate to reorient itself, leading to a slower decarboxylation
N434E
-
site-directed mutagenesis, the longer glutamine side chain sticks into the active site and causes a change in the position of malate and/or NAD+ resulting in more than a 10000fold decrease in V/Et for the mutant enzyme compared to the wild-type enzyme
N434M
-
site-directed mutagenesis, the longer methionine side chain sticks into the active site and causes a change in the position of malate and/or NAD+ resulting in more than a 10000fold decrease in V/Et for the mutant enzyme compared to the wild-type enzyme
N479Q
-
site-directed mutagenesis, the stepwise oxidative decarboxylation mechanism observed for the wild-type enzyme changed to a concerted one, which is totally rate limiting, for the N479Q mutant enzyme
N479S
-
site-directed mutagenesis, the mutant with the shorter serine side chain shows very similar values of KNAD+, Kmalate, and isotope effects relative to the wild-type enzyme, but V/Et is decreased 2000fold due to an increased freedom of rotation, resulting in nonproductively bound cofactor
R105A
-
site-directed mutagenesis, fumarate binding residue, mutant shows 7-8fold reduced initial velocity with malate and Mg2+ compared to the wild-type enzyme, and is no longer activated by fumarate and malate
R181K
-
site-directed mutagenesis, the mutant shows a 100fold increase in the Km for malate, a 30fold increase in the Ki for oxalate, and a 10fold increase in Ki for NADH, but only a slight or no change in KNAD compared to the wild-type enzyme
R181Q
-
site-directed mutagenesis, the mutant shows a 100fold increase in the Km for malate, a 30fold increase in the Ki for oxalate, and a 10fold increase in Ki for NADH, but only a slight or no change in KNAD compared to the wild-type enzyme. The activity of the R181Q mutant can be partially rescued by ammonium ion likely by binding in the pocket vacated by the guanidinium group of R181
S433A
-
site-directed mutagenesis, KNAD+ for the S433A mutant enzyme is increased by 80fold compared to the wild-type enzyme
additional information
-
construction of a chimeric enzyme NAD-ME1q, that is composed of the first 176 amino acid residues of NAD-ME2 and the central and C-terminal sequence of NAD-ME1, NAD-ME1q shows a hyperbolic behaviour for (S)-malate and NAD+. Product-inhibition pattern of NAD-ME1q with the three products supports a sequential ordered mechanism; construction of a chimeric enzyme NAD-ME1q, that is composed of the first 176 amino acid residues of NAD-ME2 and the central and C-terminal sequence of NAD-ME1, NAD-ME1q shows a hyperbolic behaviour for (S)-malate and NAD+. Product-inhibition pattern of NAD-ME1q with the three products supports a sequential ordered mechanism
additional information
-
construction of two chimeras NADME1q and NAD-ME2q by interchanging the first 176 amino residues between NAD-ME1 and -2, altered regulation in comparison to the wild-type enzymes, overview; construction of two chimeras NADME1q and NAD-ME2q by interchanging the first 176 amino residues between NAD-ME1 and -2, altered regulation in comparison to the wild-type enzymes, overview
S433C
-
site-directed mutagenesis, the mutant enzyme exhibits 9fold and 500fold increases in Kmalate and KNAD, respectively, compared to the wild-type enzyme
additional information
-
method optimization of the reverse reaction of the malic enzyme for HCO3- fixation into pyruvic acid to produce L-malic acid with NADH generation including the activity of glucose-6-phosphate dehydrogenase, EC1.1.1.49, from Leuconostoc mesenteroides
additional information
Brevundimonas diminuta IFO 13182
-
method optimization of the reverse reaction of the malic enzyme for HCO3- fixation into pyruvic acid to produce L-malic acid with NADH generation including the activity of glucose-6-phosphate dehydrogenase, EC1.1.1.49, from Leuconostoc mesenteroides
-
additional information
-
stable knockdown of ME2 in K-562 tumor cells using three independent shRNA hairpins targeting ME2, effects on K562 cell proliferation, knockout of ME2 induces erythroid differentiation, phenotype, detailed overview
additional information
-
siRNA knockdown of malic enzyme isozyme by 50% affects pyruvate carboxylase flux of the pyruvate derived from glutamate metabolism, insulin secretion in response to membrane depolarization using potassium chloride is unaffected by siRNA knockdown of malic enzyme, overview
additional information
-
siRNA knockout of ME2 in INS-1 832/13 beta-cells, siRNA knockdown and isotopic labeling strategies, method optimization, overview
additional information
-
expression of the tme gene, EC 1.1.1.40, under the control of the dme promoter, cannot restore the N2 fixation activity which is lost in dme mutant cells in alfalfa root nodules, despite elevated levels of TME within bacteroids, no symbiotic nitrogen fixation occurs in dme mutant strains, overview
additional information
B6E9W4
azc3656 mutants show about 4fold reduced NAD+-malic enzyme activity
additional information
Sinorhizobium sp. NGR234
-
azc3656 mutants show about 4fold reduced NAD+-malic enzyme activity
-
APPLICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
synthesis
-
the enzyme is useful for production of L-malic acid with NADH generation including the reverse reaction of malic enzyme and the activity of glucose-6-phosphate dehydrogenase, EC1.1.1.49, from Leuconostoc mesenteroides, overview
synthesis
Brevundimonas diminuta IFO 13182
-
the enzyme is useful for production of L-malic acid with NADH generation including the reverse reaction of malic enzyme and the activity of glucose-6-phosphate dehydrogenase, EC1.1.1.49, from Leuconostoc mesenteroides, overview
-
medicine
-
ME2 as a potentially novel metabolic target for leukemia therapy