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1.1.1.40: malate dehydrogenase (oxaloacetate-decarboxylating) (NADP+)

This is an abbreviated version!
For detailed information about malate dehydrogenase (oxaloacetate-decarboxylating) (NADP+), go to the full flat file.

Word Map on EC 1.1.1.40

Reaction

(S)-malate
+
NADP+
=
pyruvate
+
CO2
+
NADPH
+
H+

Synonyms

ADP-malic enzyme2, c-NADP-ME, C4 NADP-malic enzyme, C4 photosynthetic NADP-malic enzyme, C4-NADP-malic enzyme, C4-NADP-ME, ChlME1, ChlME2, cNAD-ME, cytoNADPME, cytosolic malic enzyme, cytosolic NADP+-dependent isoform, cytosolic NADP+-dependent malic enzyme, L-malate: NADP oxidoreductase (decarboxylating), L-malate: NADP oxidoreductase [OAA decarboxylating], L-malate: NADP oxidoreductase [oxaloacetate decarboxylating], L-malate:NADP oxidoreductase, L-malate:NADP oxidoreductase (oxaloacetate decarboxylating), m-NAD(P)-ME, m-NADP-ME, MaeB, MaeB1, MalA, malate dehydrogenase (decarboxylating, NADP), malate dehydrogenase (NADP, decarboxylating), malE1, malic enzyme, malic enzyme 1, malic enzyme 2, malic enzyme 3, malic enzyme-NADP, ME, ME-61, ME-70, ME-NADP, ME1, ME2, ME3, mitochondrial malic enzyme, mitochondrial NADP malic enzyme, mNAD-ME, NAD(P)+-malic enzyme, NADP dependent malic enzyme, NADP malic enzyme, NADP(+)-dependent mitochondrial malic enzyme 2, NADP(H)-dependent malic enzyme, NADP+ dependent malic enzyme, NADP+-dependent decarboxylating malate dehydrogenase, NADP+-dependent malic enzyme, NADP+-dependent malic enzyme 3, NADP+-dependent ME, NADP+-ME, NADP-dependent malate dehydrogenase, NADP-dependent malic enzyme, NADP-dependent malic enzyme 1, NADP-dependent ME, NADP-linked decarboxylating malic enzyme, NADP-malate dehydrogenase, NADP-malate enzyme, NADP-malic enzyme, NADP-malic enzyme 1, NADP-malic enzyme 2, NADP-MDH, NADP-ME, NADP-ME1, NADP-ME2, NADP-ME3, NADP-ME4, NADP-specific malate dehydrogenase, NADP-specific malic enzyme, NADP-specific ME, NADPH-dependent malic enzyme, NADPH-dependent malic enzyme 1, NADPH-dependent ME1, nicotinamide adenine dinucleotide phosphate-dependent malic enzyme, nicotinamide adenine dinucleotide phosphate-malic enzyme, nonC4-NADP-ME, pNAD-ME, pyruvic-malic carboxylase, RHA1_RS44255, TME

ECTree

     1 Oxidoreductases
         1.1 Acting on the CH-OH group of donors
             1.1.1 With NAD+ or NADP+ as acceptor
                1.1.1.40 malate dehydrogenase (oxaloacetate-decarboxylating) (NADP+)

Engineering

Engineering on EC 1.1.1.40 - malate dehydrogenase (oxaloacetate-decarboxylating) (NADP+)

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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
C99S
-
turnover number decreases 3fold and Km for malate increases 4fold
R70Q
-
kinetic parameters are similar except for a slightly lower turnover number and higher Km for L-malate
R115A
D235A
-
turnover number is 783.5fold lower than wild-type value
D257A
-
turnover number is 28.5fold lower than wild-type value
D258A
-
turnover number is 522fold lower than wild-type value
E234A
-
turnover number is 1.3fold higher than wild-type value
K162A
-
site-directed mutagenesis, the mutation does not affect Mn2+ binding of the mutant enzyme, but kcat is 27000fold reduced compared to the wild-type enzyme, NH4Cl shows no rescue of the pyruvate reduction in the K162A mutant, while for oxaloacetate decarboxylation, ammonium chloride demonstrated a maximum restoration of 3.5fold at 1 mM, and its rescue efficiency decreases with increasing concentration
K162Q
-
site-directed mutagenesis, the mutation does not affect Mn2+ binding of the mutant enzyme, but kcat is 3500fold reduced compared to the wild-type enzyme
K162R
-
site-directed mutagenesis,the mutation does not affect Mn2+ binding of the mutant enzyme, but kcat is 125fold reduced compared to the wild-type enzyme
K362A
-
site-directed mutagenesis, 70fold increased Km for NADP+ compared to the wild-type enzyme
W252A
-
site-directed mutagenesis, the mutant is no longer protected by Mn2+ against denaturation by urea and digestion by trypsin
W252F
-
site-directed mutagenesis, the mutant is no longer protected by Mn2+ against denaturation by urea and digestion by trypsin
W252H
-
site-directed mutagenesis, the mutant is no longer protected by Mn2+ against denaturation by urea and digestion by trypsin
W252I
-
site-directed mutagenesis, the mutant is no longer protected by Mn2+ against denaturation by urea and digestion by trypsin
W252S
-
site-directed mutagenesis, the mutant is no longer protected by Mn2+ against denaturation by urea and digestion by trypsin
Y91F
-
site-directed mutagenesis, the mutation does not affect Mn2+ binding of the mutant enzyme, the mutant shows a 25fold increase and a 3fold decrease in the Km values for (S)-malate and NADP+ respectively, and its kcat value is decreased by 200fold compared to wild-type enzyme
D139A
-
dimeric mutant enzyme with reduced activity compared to the wild type enzyme
D568A
-
dimeric or tetrameric mutant enzyme with increased activity compared to the wild type enzyme
D90A
-
dimeric or tetrameric mutant enzyme with reduced activity compared to the wild type enzyme
E314A
-
site-directed mutagenesis
E314A/S346I/K347D/K362H
-
site-directed mutagenesis, the quadruple mutant enzyme is a mainly NAD+-utilizing enzyme by a considerable increase in catalysis using NAD+ as the cofactor, shows increased inhibition by ATP compared to the wild-type enzyme
E314A/S346K
-
site-directed mutagenesis
E314A/S346K/K347Y/K362H
-
site-directed mutagenesis, the quadruple mutant enzyme is a mainly NAD+-utilizing enzyme by a considerable increase in catalysis using NAD+ as the cofactor, shows increased inhibition by ATP compared to the wild-type enzyme
E314A/S346K/K347Y/K362Q
-
site-directed mutagenesis, the quadruple mutant enzyme is a mainly NAD+-utilizing enzyme by a considerable increase in catalysis using NAD+ as the cofactor, shows increased inhibition by ATP compared to the wild-type enzyme
H142A
H142A/D568A
H51A
-
dimeric or tetrameric mutant enzyme with wild type activity
H51A/D139A
H51A/D90A
K347Y
-
site-directed mutagenesis, the mutant enzyme shows a 5fold increased Km for NADP+ compared to the wild-type enzyme
K347Y/K362Q
-
site-directed mutagenesis
K362H
-
site-directed mutagenesis
K362Q
-
site-directed mutagenesis, the mutant enzyme displays a significant, over 140fold elevation in Km,NADP value compared with that of wild-type c-NADP-ME but no significant changes in the kcat,NADP value
K57S/E59N/K73E/D102S
site-directed mutagenesis, the mutant is primarily monomeric with some dimer formation
N59E/E73K
N59E/E73K/S102D
S102D
S346I/K347D/K362H
-
site-directed mutagenesis, the triple c-NADP-ME mutant does not show significant reduction in its Km,NAD values. This mutant exclusively utilizes NAD+ as its cofactor
S346K
-
site-directed mutagenesis, site-directed mutagenesis, the mutant enzyme shows a 3fold increased Km for NADP+ compared to the wild-type enzyme
S346K/K347Y
-
site-directed mutagenesis, the double mutant enzyme shows a 30fold increased Km for NADP+ compared to the wild-type enzyme
S346K/K347Y/K362H
-
site-directed mutagenesis, the triple c-NADP-ME mutant does not show significant reduction in its Km,NAD values, but displays an enhanced value for kcat,NAD
S346K/K347Y/K362Q
-
site-directed mutagenesis, the triple c-NADP-ME mutant does not show significant reduction in its Km,NAD values
S346K/K362Q
-
site-directed mutagenesis
S57K/N59E/E73K
S57K/N59E/E73K/S102D
S57K/N59E/E73K/S102D/H74K/D78P/D80E/D87G
S57K/N59E/E73K/S102D/H74K/D78P/D80E/D87G/D90E/K106S/Q121S/L125H
S57K/N59E/E73K/S102D/H74K/D78P/D80E/D87G/K106S/Q121S/L125H
W572A
moe
-
enzyme inactivation by shRNA, ME1 activity is reduced by 62% and glucose-induced insulin secretion is decreased
I310V
site-directed mutagenesis
K228R
site-directed mutagenesis
R221G
site-directed mutagenesis
R221G/K228R
site-directed mutagenesis, substitution of Arg221 with Gly is responsible for the shift in reaction specificity
R221G/K228R/I310V
site-directed mutagenesis, the reaction specificity of the triple mutant is significantly shifted to malate production and the mutant gives a reduced amount of the byproduct than the wild-type. When the triple mutant enzyme is used as a catalyst for pyruvate carboxylation with NADH, the enzyme gives 1.2times higher concentration of malate than the wild-type with NADPH. Single-point mutation analysis reveals that the substitution of Arg221 with Gly is responsible for the shift in reaction specificity
V393V
1179 GTC /GTT results in a synonymous mutation of V393V
A339E
-
the mutant of isoform nonC4-NADP-ME shows increased catalytic efficiency compared to the wild type enzyme
A387G
site directed mutagenesis, mutation at the NADP+ binding site, mutant shows 48fold decreased kcat and 4.3 and 5.8fold increased Km for NADP+ and L-malate, respectively, compared to the wild-type enzyme, no activity with NAD+
A392G
site directed mutagenesis, mutation at the NADP+ binding site, mutant shows unaltered kcat, but 3.5 and 2.6fold increased Km for NADP+ and L-malate, respectively, and increased activity with NAD+ compared to the wild-type enzyme
C192A
C231A
C246A
C270A
DelN
-
the mutant of isoform nonC4-NADP-ME shows reduced catalytic efficiency compared to the wild type enzyme and is not inhibited by (S)-malate
DelN/A339E
-
the mutant of isoform nonC4-NADP-ME shows reduced catalytic efficiency compared to the wild type enzyme
DelN/I140F/A339E
-
the mutant of isoform nonC4-NADP-ME shows increased catalytic efficiency compared to the wild type enzyme and is not inhibited by (S)-malate
E339A
-
the mutant of isoform C4-NADP-ME shows reduced catalytic efficiency compared to the wild type enzyme and is not inhibited by (S)-malate
F140I
-
the mutant of isoform C4-NADP-ME shows reduced catalytic efficiency compared to the wild type enzyme
I140F
-
the mutant of isoform nonC4-NADP-ME shows reduced catalytic efficiency compared to the wild type enzyme and is not inhibited by (S)-malate
I140F/A339E
-
the mutant of isoform nonC4-NADP-ME shows reduced catalytic efficiency compared to the wild type enzyme and is not inhibited by (S)-malate
K225I
-
site-directed mutagenesis, mutation of a conserved residue involved in catalysis and substrate binding, mutant shows highly reduced activity and a 10fold higher partitioning ratio of oxaloacetate and malate compared to the wild-type enzyme, preference for reduction of oxaloacetate instead of decarboxylation
K435L/K436L
-
site-directed mutagenesis, mutation of residues which are important in cofactor binding, over 6fold increased Ki for 2'-AMP, and 1.7fold decreased Ki for 5'-AMP, and increased activity with NAD+ compared to the wild-type enzyme
L544F
-
the mutant of isoform C4-NADP-ME shows reduced catalytic efficiency compared to the wild type enzyme
Q503E
-
the mutant of isoform C4-NADP-ME shows reduced catalytic efficiency compared to the wild type enzyme
R237L
S419A
the variant presents 72.3% of the wild type activity
S419E
the variant presents 8.7% of the wild type activity. The mutation dramatically decreases the affinity for the cofactor, as saturation is not observed even at NADP+ concentrations as high as 5 mM
additional information