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Information on EC 1.1.1.39 - malate dehydrogenase (decarboxylating) and Organism(s) Arabidopsis thaliana and UniProt Accession Q8L7K9
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1.1.1.39 malate dehydrogenase (decarboxylating)IUBMB Comments
There are several forms of malate dehydrogenases that differ in their use of substrates and cofactors. This particular form is found only in the plant kingdom. Unlike EC 1.1.1.38, which catalyses a similar reaction, this enzyme can not bind oxaloacetate, and thus does not decarboxylate exogeneously-added oxaloacetate. cf. EC 1.1.1.37, malate dehydrogenase; EC 1.1.1.38, malate dehydrogenase (oxaloacetate-decarboxylating); and EC 1.1.1.83, D-malate dehydrogenase (decarboxylating).
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Word Map
- 1.1.1.39
- nadp
- fumarate
-
nadp+-dependent
- l-malate
- alpha-glycerophosphate
- hydrogenosomes
-
crassulacean
-
nad+-malic
-
alpha-gpd
- synthesis
- medicine
The taxonomic range for the selected organisms is: Arabidopsis thaliana
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota
Synonyms
mitochondrial malic enzyme, cytosolic malic enzyme, malate dehydrogenase (decarboxylating), nad-me1, nad-dependent malic enzyme, nad-me2, m-nad-me, nad-meh, nad-preferring malic enzyme, nad-dependent malic enzyme 1, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
dehydrogenase, malate
-
-
-
-
DMA
-
-
-
-
malic enzyme
-
-
-
-
ME
-
-
-
-
NAD-malic enzyme
NAD-ME
-
-
-
-
NAD-MEH
NAD-specific malic enzyme
-
-
-
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pyruvic-malic carboxylase
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-
-
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NAD-malic enzyme
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-
-
-
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
(S)-malate + NAD+ = pyruvate + CO2 + NADH
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
(S)-malate + NAD+ = pyruvate + CO2 + NADH
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
COMMENTARY
LITERATURE
redox reaction
-
-
-
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oxidation
-
-
-
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reduction
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-
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oxidative decarboxylation
-
-
-
-
PATHWAY SOURCE
PATHWAYS
BRENDA
SYSTEMATIC NAME
IUBMB Comments
(S)-malate:NAD+ oxidoreductase (decarboxylating)
There are several forms of malate dehydrogenases that differ in their use of substrates and cofactors. This particular form is found only in the plant kingdom. Unlike EC 1.1.1.38, which catalyses a similar reaction, this enzyme can not bind oxaloacetate, and thus does not decarboxylate exogeneously-added oxaloacetate. cf. EC 1.1.1.37, malate dehydrogenase; EC 1.1.1.38, malate dehydrogenase (oxaloacetate-decarboxylating); and EC 1.1.1.83, D-malate dehydrogenase (decarboxylating).
CAS REGISTRY NUMBER
COMMENTARY
9028-46-0
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
(S)-malate + NAD+
pyruvate + CO2 + NADH
the enzyme plays a central role in the metabolite flux through the tricarboxylic acid cycle, overview
-
-
r
(S)-malate + NAD+
pyruvate + NADH + H+ + CO2
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
very low activity in the reverse reaction in vitro
-
-
r
(S)-malate + NAD+
pyruvate + CO2 + NADH
the enzyme plays a central role in the metabolite flux through the tricarboxylic acid cycle, overview
-
-
r
(S)-malate + NAD+
pyruvate + NADH + H+ + CO2
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
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
very low activity in the reverse reaction in vitro
-
-
r
additional information
?
-
-
NAD-ME2 does not perform decarboxylation of oxaloacetate
-
-
?
additional information
?
-
NAD-ME2 does not perform decarboxylation of oxaloacetate
-
-
?
additional information
?
-
NAD-ME2 does not perform decarboxylation of oxaloacetate
-
-
?
additional information
?
-
NAD-ME1 has a regulatory site for L-malate that can also bind fumarate
-
-
?
additional information
?
-
NAD-ME1 has a regulatory site for L-malate that can also bind fumarate
-
-
?
additional information
?
-
the enzyme is unable to decarboxylate oxaloacetate
-
-
-
additional information
?
-
the enzyme is unable to decarboxylate oxaloacetate
-
-
-
additional information
?
-
-
NAD-ME1 does not perform decarboxylation of oxaloacetate
-
-
?
additional information
?
-
NAD-ME1 does not perform decarboxylation of oxaloacetate
-
-
?
additional information
?
-
NAD-ME1 does not perform decarboxylation of oxaloacetate
-
-
?
additional information
?
-
-
NAD-MEH does not perform decarboxylation of oxaloacetate
-
-
?
additional information
?
-
NAD-MEH does not perform decarboxylation of oxaloacetate
-
-
?
additional information
?
-
NAD-MEH does not perform decarboxylation of oxaloacetate
-
-
?
additional information
?
-
NAD-ME1 has a regulatory site for L-malate that can also bind fumarate. L-Malate binding to this site elicits a sigmoidal and low substrate-affinity response, whereas fumarate binding turns NAD-ME1 into a hyperbolic and high substrate affinity enzyme. This effect is also observed when the allosteric site is either removed or altered. Fumarate is not really an activator, but suppresses the inhibitory effect of L-malate. Residues Arg50, Arg80 and Arg84 show different roles in organic acid binding. These residues form a triad, which is the basis of the homo and heterotrophic effects that characterize NAD-ME1
-
-
?
additional information
?
-
NAD-ME1 has a regulatory site for L-malate that can also bind fumarate. L-Malate binding to this site elicits a sigmoidal and low substrate-affinity response, whereas fumarate binding turns NAD-ME1 into a hyperbolic and high substrate affinity enzyme. This effect is also observed when the allosteric site is either removed or altered. Fumarate is not really an activator, but suppresses the inhibitory effect of L-malate. Residues Arg50, Arg80 and Arg84 show different roles in organic acid binding. These residues form a triad, which is the basis of the homo and heterotrophic effects that characterize NAD-ME1
-
-
?
additional information
?
-
the enzyme is unable to decarboxylate oxaloacetate
-
-
-
additional information
?
-
the enzyme is unable to decarboxylate oxaloacetate
-
-
-
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
(S)-malate + NAD+
pyruvate + CO2 + NADH
the enzyme plays a central role in the metabolite flux through the tricarboxylic acid cycle, overview
-
-
r
(S)-malate + NAD+
pyruvate + NADH + H+ + CO2
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 + CO2 + NADH
the enzyme plays a central role in the metabolite flux through the tricarboxylic acid cycle, overview
-
-
r
(S)-malate + NAD+
pyruvate + NADH + H+ + CO2
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
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Mg2+
a divalent metal ion, Mn+2 or Mg+2+, is essential for the enzyme reaction
Mn2+
Mg2+
a divalent metal ion, Mn+2 or Mg+2+, is essential for the enzyme reaction
Mn2+
Mn2+
a divalent metal ion, Mn+2 or Mg+2+, is essential for the enzyme reaction
Mn2+
a divalent metal ion, Mn+2 or Mg+2+, is essential for the enzyme reaction
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
5'-AMP
isozyme NAD-ME2, competitive versus NAD+, mixed inhibition versus (S)-malate
CO2
isozyme NAD-ME2 and chimeric mutant NAD-ME1q, mixed inhibition versus NAD+ and (S)-malate
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
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
Tartrate
substrate analogue, isozyme NAD-ME2, uncompetitive versus NAD+, competitive versus (S)-malate
CO2
chimeric mutant NAD-ME1q, mixed inhibition versus NAD+ and (S)-malate
NADH
NADH shows competitive and mixed-type inhibition versus NAD+ and (S)-malate with chimeric mutant NAD-ME1q
pyruvate
pyruvate inhibition is uncompetitive with respect to NAD+ and mixed with respect to (S)-malate for the chimeric mutant NAD-ME1q
additional information
product inhibition patterns of isozyme NAD-ME2, overview
-
additional information
product inhibition patterns of isozyme NAD-ME2, overview
-
additional information
-
product inhibition patterns of isozyme NAD-ME2, overview
-
additional information
product inhibition patterns of isozyme NAD-ME2, overview
-
additional information
product inhibition patterns of isozyme NAD-ME2, overview
-
additional information
-
product inhibition patterns of isozyme NAD-ME2, overview
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
fumarate
Arabidopsis NAD-ME1 is strongly stimulated by fumarate. Fumarate binding turns NAD-ME1 into a hyperbolic and high substrate affinity enzyme. This effect is also observed when the allosteric site is either removed or altered. Hence, fumarate is not really an activator, but suppresses the inhibitory effect of L-malate. Binding of L-malate and fumarate at the same allosteric site
fumarate
Arabidopsis NAD-ME1 is strongly stimulated by fumarate. Fumarate binding turns NAD-ME1 into a hyperbolic and high substrate affinity enzyme. This effect is also observed when the allosteric site is either removed or altered. Hence, fumarate is not really an activator, but suppresses the inhibitory effect of L-malate. Binding of L-malate and fumarate at the same allosteric site. Arg84 is essential for fumarate activation
additional information
-
no activation by oxaloacetate, poor activation by ATP and AMP
-
additional information
no activation by oxaloacetate, poor activation by ATP and AMP
-
additional information
no activation by oxaloacetate, poor activation by ATP and AMP
-
additional information
-
no activation by CoA and acetyl-CoA, poor activation by ATP and AMP
-
additional information
no activation by CoA and acetyl-CoA, poor activation by ATP and AMP
-
additional information
no activation by CoA and acetyl-CoA, poor activation by ATP and AMP
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
2.6
(S)-malate
isozyme NAD-ME2, pH 6.5, temperature not specified in the publication
3
(S)-malate
pH 6.6, temperature not specified in the publication, NAD-ME2
0.5
NAD+
pH 6.6, temperature not specified in the publication, NAD-ME2
1.1
NAD+
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
3
(S)-malate
pH 6.4, temperature not specified in the publication, NAD-ME1
0.5
NAD+
pH 6.4, temperature not specified in the publication, NAD-ME1
0.55
NAD+
pH 6.5, temperature not specified in the publication, NAD-MEH
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
-
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
-
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
-
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
-
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
-
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
-
additional information
additional information
NAD-ME2 shows a typical hyperbolic behavior
-
additional information
additional information
NAD-ME2 shows a typical hyperbolic behavior
-
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
-
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
-
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
-
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. Kinetic properties and mechanism of chimeric mutant NAD-ME1q, 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. Kinetic properties and mechanism of chimeric mutant NAD-ME1q, 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. Kinetic properties and mechanism of chimeric mutant NAD-ME1q, overview
-
additional information
additional information
Arabidopsis NAD-ME1 exhibits a non-hyperbolic behavior for the substrate L-malate and presents a sigmoidal kinetic response for L-malate. Fumarate binding turns NAD-ME1 into a hyperbolic and high substrate affinity enzyme, overview
-
additional information
additional information
Arabidopsis NAD-ME1 exhibits a non-hyperbolic behavior for the substrate L-malate and presents a sigmoidal kinetic response for L-malate. Fumarate binding turns NAD-ME1 into a hyperbolic and high substrate affinity enzyme, overview
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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
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
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
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
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
14.7
(S)-malate
pH 6.6, temperature not specified in the publication, NAD-ME2
88.2
NAD+
pH 6.6, temperature not specified in the publication, NAD-ME2
10.3
(S)-malate
pH 6.4, temperature not specified in the publication, NAD-ME1
14.2
(S)-malate
pH 6.5, temperature not specified in the publication, NAD-MEH
60.2
NAD+
pH 6.4, temperature not specified in the publication, NAD-ME1
67
NAD+
pH 6.5, temperature not specified in the publication, NAD-MEH
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
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
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
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
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6.6
6.4
6.5
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
isozyme NAD-ME2; isozyme NAD-ME2 encoded by gene AtNAD-ME2
UniProt
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
NAD-ME1and -2 subunits show a distinct patterns of accumulation in the separate components of the floral organ
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
additional information
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
NAD-ME1and -2 subunits show a distinct patterns of accumulation in the separate components of the floral organ
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
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
additional information
tissue specific expression of the isozyme, overview
additional information
tissue specific expression of the isozyme, overview
additional information
tissue specific expression of the isozyme, overview
additional information
tissue specific expression of the isozyme, overview
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
physiological function
physiological function
additional information
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
physiological function
plant mitochondria can use L-malate and fumarate, which accumulate in large levels, as respiratory substrates. In part, this property is due to the presence of NAD-dependent malic enzymes (NAD-ME). Malic enzyme tracers reveal hypoxia-induced switch in adipocyte NADPH pathway usage
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
physiological function
Plant mitochondria can use L-malate and fumarate, which accumulate in large levels, as respiratory substrates. In part, this property is due to the presence of NAD-dependent malic enzymes (NAD-ME). Malic enzyme tracers reveal hypoxia-induced switch in adipocyte NADPH pathway usage. Important role of NAD-ME1 in processes that control flow of C4 organic acids in Arabidopsis mitochondrial metabolism.. NAD-ME1 exhibits a complex homo and heterotrophic allosteric regulation with L-malate wielding an inhibitory effect that is cancelled by competitive fumarate binding
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
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
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
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
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
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
additional information
mutants and chimeric proteins of NAD-ME1 and -2 indicated that the amino-terminal region of NAD-ME1 is implicated in fumarate activation and sigmoidal L-malate responses, structure-function analysis, overview
additional information
mutants and chimeric proteins of NAD-ME1 and -2 indicated that the amino-terminal region of NAD-ME1 is implicated in fumarate activation and sigmoidal L-malate responses, structure-function analysis, overview
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
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
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
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
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
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
additional information
residues Arg50, Arg80 and Arg84 show different roles in organic acid binding. These residues form a triad, which is the basis of the homo and heterotrophic effects that characterize NAD-ME1. Mutants and chimeric proteins of NAD-ME1 and -2 indicated that the amino-terminal region of NAD-ME1 is implicated in fumarate activation and sigmoidal L-malate responses, structure-function analysis, overview
additional information
residues Arg50, Arg80 and Arg84 show different roles in organic acid binding. These residues form a triad, which is the basis of the homo and heterotrophic effects that characterize NAD-ME1. Mutants and chimeric proteins of NAD-ME1 and -2 indicated that the amino-terminal region of NAD-ME1 is implicated in fumarate activation and sigmoidal L-malate responses, structure-function analysis, overview
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). MAO2_ARATH
607
0
66641
Swiss-Prot
Mitochondrion (Reliability: 3)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
dimer
additional information
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
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
additional information
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
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-ME2 primary structure and domain analysis, overview
additional information
isozyme NAD-ME2 primary structure and domain analysis, overview
additional information
isozyme NAD-ME2 primary structure and domain analysis, overview
additional information
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
additional information
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
additional information
-
isozyme NAD-ME1 primary structure and domain analysis, overview
additional information
isozyme NAD-ME1 primary structure and domain analysis, overview
additional information
isozyme NAD-ME1 primary structure and domain analysis, overview
additional information
-
isozyme NAD-MEH primary structure and domain analysis, overview
additional information
isozyme NAD-MEH primary structure and domain analysis, overview
additional information
isozyme NAD-MEH primary structure and domain analysis, overview
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
R50A
site-directed mutagenesis, the mutant does not show altered kinetics after addition of fumarate
R80A
site-directed mutagenesis, the mutant shows altered kinetics after addition of fumarate
R84A
site-directed mutagenesis, the mutant does not show altered kinetics after addition of fumarate
additional information
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
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
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
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
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
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
additional information
mutants and chimeric proteins of NAD-ME1 and -2 indicated that the amino-terminal region of NAD-ME1 is implicated in fumarate activation and sigmoidal L-malate responses, structure-function analysis, overview. Generation of the chimeric protein NAD-ME2q, that possesses the first 176 amino acid residues of NAD-ME1 and the central and C-terminal sequence of NAD-ME2, presents a sigmoidal L-malate response similar to the one for NAD-ME1, but also a higher Km L-malate value and a lower kcat value. NAD-ME2q is activated by fumarate and an increase in its concentration produces a decrease in Km and nH values. At 4 mM fumarate, the Lmalate saturation curve is hyperbolic (nH = 1.1) with an 8fold decrease in Km value. There are no significant changes in kcat value by addition of fumarate, which implies a 9fold increase in NAD-ME2q catalytic efficiency when compared to the enzyme in the absence of fumarate
additional information
mutants and chimeric proteins of NAD-ME1 and -2 indicated that the amino-terminal region of NAD-ME1 is implicated in fumarate activation and sigmoidal L-malate responses, structure-function analysis, overview. Generation of the chimeric protein NAD-ME2q, that possesses the first 176 amino acid residues of NAD-ME1 and the central and C-terminal sequence of NAD-ME2, presents a sigmoidal L-malate response similar to the one for NAD-ME1, but also a higher Km L-malate value and a lower kcat value. NAD-ME2q is activated by fumarate and an increase in its concentration produces a decrease in Km and nH values. At 4 mM fumarate, the Lmalate saturation curve is hyperbolic (nH = 1.1) with an 8fold decrease in Km value. There are no significant changes in kcat value by addition of fumarate, which implies a 9fold increase in NAD-ME2q catalytic efficiency when compared to the enzyme in the absence of fumarate
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
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
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
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
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
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
additional information
mutants and chimeric proteins of NAD-ME1 and -2 indicated that the amino-terminal region of NAD-ME1 is implicated in fumarate activation and sigmoidal L-malate responses, structure-function analysis, overview. Generation of chimeric protein NAD-ME1q, which is composed of the first 176 amino acid residues of isozyme NAD-ME2 and the central and C-terminal sequence of isozyme NAD-ME1, exhibits a significantly lower Km L-malate value than the parental isoforms and a hyperbolic behavior that is not modified by fumarate
additional information
mutants and chimeric proteins of NAD-ME1 and -2 indicated that the amino-terminal region of NAD-ME1 is implicated in fumarate activation and sigmoidal L-malate responses, structure-function analysis, overview. Generation of chimeric protein NAD-ME1q, which is composed of the first 176 amino acid residues of isozyme NAD-ME2 and the central and C-terminal sequence of isozyme NAD-ME1, exhibits a significantly lower Km L-malate value than the parental isoforms and a hyperbolic behavior that is not modified by fumarate
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
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-ME1 and mutants NADME1q and NAD-ME2q from Escherichia coli strain BL21(DE3) by nickel affinity chromatography and gel filtration
recombinant His-tagged NAD-MEH from Escherichia coli strain BL21(DE3) by nickel affinity chromatography and gel filtration
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression of His-tagged NAD-ME2 and mutants NADME1q and NAD-ME2q in Escherichia coli strain BL21(DE3)
gene AtNAD-ME2, DNA and amino acid sequence determination and analysis, phylogenetic tree
expression of His-tagged NAD-ME1 and of 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
recombinant expression of His-tagged wild-type and mutant enzymes in Escherichia coli strain BL21(DE3)
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Tronconi, M.A.; Fahnenstich, H.; Gerrard Weehler, M.C.; Andreo, C.S.; Fluegge, U.I.; Drincovich, M.F.; Maurino, V.G.
Arabidopsis NAD-malic enzyme functions as a homodimer and heterodimer and has a major impact on nocturnal metabolism
Plant Physiol.
146
1540-1552
2008
Arabidopsis thaliana (Q8L7K9), Arabidopsis thaliana (Q9SIU0)
Tronconi, M.A.; Gerrard Wheeler, M.C.; Maurino, V.G.; Drincovich, M.F.; Andreo, C.S.
NAD-malic enzymes of Arabidopsis thaliana display distinct kinetic mechanisms that support differences in physiological control
Biochem. J.
430
295-303
2010
Arabidopsis thaliana (Q8L7K9), Arabidopsis thaliana (Q9SIU0), Arabidopsis thaliana
Tronconi, M.A.; Maurino, V.G.; Andreo, C.S.; Drincovich, M.F.
Three different and tissue-specific NAD-malic enzymes generated by alternative subunit association in Arabidopsis thaliana
J. Biol. Chem.
285
11870-11879
2010
Arabidopsis thaliana, Arabidopsis thaliana (Q8L7K9), Arabidopsis thaliana (Q9SIU0)
Tronconi, M.A.; Wheeler, M.C.; Martinatto, A.; Zubimendi, J.P.; Andreo, C.S.; Drincovich, M.F.
Allosteric substrate inhibition of Arabidopsis NAD-dependent malic enzyme 1 is released by fumarate
Phytochemistry
111
37-47
2015
Arabidopsis thaliana (Q8L7K9), Arabidopsis thaliana (Q9SIU0)
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