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Literature summary for 1.1.1.40 extracted from

  • Hsieh, J.Y.; Chen, M.C.; Hung, H.C.
    Determinants of nucleotide-binding selectivity of malic enzyme (2011), PLoS ONE, 6, e25312.
    View publication on PubMedView publication on EuropePMC
Search for more literature for 1.1.1.40

Protein Variants

Protein Variants Comment Organism
E314A site-directed mutagenesis Homo sapiens
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 Homo sapiens
E314A/S346K site-directed mutagenesis Homo sapiens
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 Homo sapiens
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 Homo sapiens
K347Y site-directed mutagenesis, the mutant enzyme shows a 5fold increased Km for NADP+ compared to the wild-type enzyme Homo sapiens
K347Y/K362Q site-directed mutagenesis Homo sapiens
K362H site-directed mutagenesis Homo sapiens
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 Homo sapiens
additional information a series of E314A-containing c-NADP-ME quadruple mutants are changed to NAD+-utilizing enzymes by abrogating NADP+ binding and increasing NAD+ binding. Abolishing the repulsive effect of Glu314 in the quadruple mutants increases the binding affinity of NAD+ Homo sapiens
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 Homo sapiens
S346K site-directed mutagenesis, site-directed mutagenesis, the mutant enzyme shows a 3fold increased Km for NADP+ compared to the wild-type enzyme Homo sapiens
S346K/K347Y site-directed mutagenesis, the double mutant enzyme shows a 30fold increased Km for NADP+ compared to the wild-type enzyme Homo sapiens
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 Homo sapiens
S346K/K347Y/K362Q site-directed mutagenesis, the triple c-NADP-ME mutant does not show significant reduction in its Km,NAD values Homo sapiens
S346K/K362Q site-directed mutagenesis Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
ATP 10% inhibition of the wild-type enzyme at 3.0 mM in presence of NAD+, no inhibition in presence of NADP+, inhibition of mutant enzymes by ATP inpresence of NAD+ or NADP+ Homo sapiens

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
additional information
-
 additional information human m-NAD(P)-ME is a non-cooperative enzyme for substrate L-malate binding, steady-state kinetics of wild-type and mutant enzymes, overview Homo sapiens
0.002
-
 NADP+ mutant E314A, pH 7.4, 30°C Homo sapiens
0.003
-
 NADP+ mutant E314A/S346K, pH 7.4, 30°C Homo sapiens
0.005
-
 NADP+ wild-type enzyme, pH 7.4, 30°C Homo sapiens
0.013
-
 NADP+ mutant S346K, pH 7.4, 30°C Homo sapiens
0.03
-
 NADP+ mutant K347Y, pH 7.4, 30°C Homo sapiens
0.14
-
 NADP+ mutant S346K/K347Y, pH 7.4, 30°C Homo sapiens
0.36
-
 NADP+ mutant K362H, pH 7.4, 30°C Homo sapiens
0.4
-
 (S)-malate mutant E314A, with NADP+, pH 7.4, 30°C Homo sapiens
0.76
-
 NADP+ mutant K362Q, pH 7.4, 30°C Homo sapiens
0.9
-
 (S)-malate mutant S346K, with NADP+, pH 7.4, 30°C Homo sapiens
0.9
-
 NAD+ mutants E314A/S346K/K347Y/K362H and E314A/S346I/K347D/K362H, pH 7.4, 30°C Homo sapiens
1
-
 (S)-malate mutant E314A/S346K/K347Y/K362H, with NAD+, pH 7.4, 30°C Homo sapiens
1
-
 (S)-malate mutant S346K/K347Y, with NADP+, pH 7.4, 30°C Homo sapiens
1
-
 (S)-malate with NADP+, wild-type enzyme, pH 7.4, 30°C Homo sapiens
1.2
-
 (S)-malate mutant E314A/S346K, with NADP+, pH 7.4, 30°C Homo sapiens
1.5
-
 NAD+ mutant E314A/S346K/K347Y/K362Q, pH 7.4, 30°C Homo sapiens
1.6
-
 NAD+ mutant E314A, pH 7.4, 30°C Homo sapiens
1.8
-
 (S)-malate mutants K347Y and K362Q, with NADP+, pH 7.4, 30°C Homo sapiens
2
-
 (S)-malate mutant E314A/S346K/K347Y/K362Q, with NAD+, pH 7.4, 30°C Homo sapiens
3
-
 (S)-malate mutant E314A/S346I/K347D/K362H, with NAD+, pH 7.4, 30°C Homo sapiens
3
-
 NADP+ mutant E314A/S346K/K347Y/K362H, pH 7.4, 30°C Homo sapiens
3.7
-
 (S)-malate mutant S346K/K362Q, with NADP+, pH 7.4, 30°C Homo sapiens
4
-
 (S)-malate mutants E314A, S346K, E314A/S346K, S346K/K362Q, and S346K/K347Y/K362Q, with NAD+, pH 7.4, 30°C Homo sapiens
4.9
-
 (S)-malate mutant K362H, with NADP+, pH 7.4, 30°C Homo sapiens
5
-
 NAD+ mutant E314A/S346K, pH 7.4, 30°C Homo sapiens
5
-
 NADP+ mutant E314A/S346K/K347Y/K362Q, pH 7.4, 30°C Homo sapiens
5
-
 (S)-malate mutants K347Y, K362Q, and S346K/K347Y, with NAD+, pH 7.4, 30°C Homo sapiens
5
-
 (S)-malate with NAD+, wild-type enzyme, pH 7.4, 30°C Homo sapiens
5.5
-
 (S)-malate mutant S347Y/K362Q, with NADP+, pH 7.4, 30°C Homo sapiens
5.6
-
 (S)-malate mutant E314A/S346K/K347Y/K362Q, with NADP+, pH 7.4, 30°C Homo sapiens
6
-
 NADP+ mutant S346K/K362Q, pH 7.4, 30°C Homo sapiens
6
-
 (S)-malate mutants S346K/K347Y/K362H, with NAD+, pH 7.4, 30°C Homo sapiens
6.5
-
 NAD+ mutant S346I/K347D/K362H, pH 7.4, 30°C Homo sapiens
7
-
 (S)-malate mutant S346I/K347D/K362H, with NAD+, pH 7.4, 30°C Homo sapiens
7.1
-
 NAD+ mutant S346K/K347Y/K362H, pH 7.4, 30°C Homo sapiens
7.3
-
 (S)-malate mutant E314A/S346K/K347Y/K362H, with NADP+, pH 7.4, 30°C Homo sapiens
8
-
 (S)-malate mutants K362H and S347Y/K362Q, with NAD+, pH 7.4, 30°C Homo sapiens
10
-
 NAD+ mutant S346K/K347Y/K362Q, pH 7.4, 30°C Homo sapiens
10
-
 (S)-malate mutant S346K/K347Y/K362Q, with NADP+, pH 7.4, 30°C Homo sapiens
11
-
 NAD+ mutant K347Y, pH 7.4, 30°C Homo sapiens
11
-
 (S)-malate mutant S346K/K347Y/K362H, with NADP+, pH 7.4, 30°C Homo sapiens
12
-
 NADP+ mutant S347Y/K362Q, pH 7.4, 30°C Homo sapiens
13
-
 NAD+ mutant K362Q, pH 7.4, 30°C Homo sapiens
14
-
 NAD+ mutant K362H, pH 7.4, 30°C Homo sapiens
14
-
 NAD+ mutant S346K/K362Q, pH 7.4, 30°C Homo sapiens
17
-
 NAD+ mutant S346K, pH 7.4, 30°C Homo sapiens
17
-
 NADP+ mutant S346K/K347Y/K362Q, pH 7.4, 30°C Homo sapiens
18
-
 NAD+ mutant S346K/K347Y, pH 7.4, 30°C Homo sapiens
18.35
-
 NAD+ wild-type enzyme, pH 7.4, 30°C Homo sapiens
20
-
 NAD+ mutant S347Y/K362Q, pH 7.4, 30°C Homo sapiens
24
-
 (S)-malate mutant E314A/S346I/K347D/K362H, with NADP+, pH 7.4, 30°C Homo sapiens
29
-
 NADP+ mutants S346K/K347Y/K362H and E314A/S346I/K347D/K362H, pH 7.4, 30°C Homo sapiens
36
-
 (S)-malate mutant S346I/K347D/K362H, with NADP+, pH 7.4, 30°C Homo sapiens
116
-
 NADP+ mutant S346I/K347D/K362H, pH 7.4, 30°C Homo sapiens

Localization

Localization Comment Organism GeneOntology No. Textmining
cytosol
-
 Homo sapiens 5829
-

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
(S)-malate + NADP+ Homo sapiens
-
 pyruvate + CO2 + NADPH
-
 r

Organism

Organism UniProt Comment Textmining
Homo sapiens
-
-
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
(S)-malate + NAD+
-
 Homo sapiens pyruvate + CO2 + NADH
-
 r
(S)-malate + NADP+
-
 Homo sapiens pyruvate + CO2 + NADPH
-
 r

Synonyms

Synonyms Comment Organism
c-NADP-ME
-
 Homo sapiens

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
37
-
 assay at Homo sapiens

Turnover Number [1/s]

Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
1.3
-
 NADP+ mutant S346I/K347D/K362H, pH 7.4, 30°C Homo sapiens
8
-
 NADP+ mutant S346K/K347Y/K362H, pH 7.4, 30°C Homo sapiens
15
-
 NADP+ mutant E314A/S346I/K347D/K362H, pH 7.4, 30°C Homo sapiens
15
-
 NADP+ mutant S346K/K347Y/K362Q, pH 7.4, 30°C Homo sapiens
22
-
 NAD+ mutant S346K, pH 7.4, 30°C Homo sapiens
26
-
 NADP+ mutant E314A/S346K/K347Y/K362H, pH 7.4, 30°C Homo sapiens
40
-
 NAD+ mutant K347Y, pH 7.4, 30°C Homo sapiens
51
-
 NADP+ mutant E314A/S346K/K347Y/K362Q, pH 7.4, 30°C Homo sapiens
51
-
 NAD+ wild-type enzyme, pH 7.4, 30°C Homo sapiens
53
-
 NAD+ mutant S347Y/K362Q, pH 7.4, 30°C Homo sapiens
60
-
 NAD+ mutant K362Q, pH 7.4, 30°C Homo sapiens
65
-
 NAD+ mutant S346K/K347Y, pH 7.4, 30°C Homo sapiens
78
-
 NADP+ mutant S347Y/K362Q, pH 7.4, 30°C Homo sapiens
102
-
 NADP+ mutant S346K/K347Y, pH 7.4, 30°C Homo sapiens
108
-
 NAD+ mutant K362H, pH 7.4, 30°C Homo sapiens
110
-
 NADP+ mutant E314A, pH 7.4, 30°C Homo sapiens
110
-
 NAD+ mutant S346K/K362Q, pH 7.4, 30°C Homo sapiens
112
-
 NADP+ mutant S346K/K362Q, pH 7.4, 30°C Homo sapiens
113
-
 NAD+ mutant E314A, pH 7.4, 30°C Homo sapiens
121
-
 NADP+ mutant K347Y, pH 7.4, 30°C Homo sapiens
124
-
 NAD+ mutant S346K/K347Y/K362Q, pH 7.4, 30°C Homo sapiens
126
-
 NADP+ wild-type enzyme, pH 7.4, 30°C Homo sapiens
129
-
 NADP+ mutant S346K, pH 7.4, 30°C Homo sapiens
131
-
 NAD+ mutant S346I/K347D/K362H, pH 7.4, 30°C Homo sapiens
132
-
 NADP+ mutant K362Q, pH 7.4, 30°C Homo sapiens
137
-
 NADP+ mutant E314A/S346K, pH 7.4, 30°C Homo sapiens
145
-
 NAD+ mutant E314A/S346K, pH 7.4, 30°C Homo sapiens
149
-
 NADP+ mutant K362H, pH 7.4, 30°C Homo sapiens
166
-
 NAD+ mutant E314A/S346I/K347D/K362H, pH 7.4, 30°C Homo sapiens
208
-
 NAD+ mutant E314A/S346K/K347Y/K362Q, pH 7.4, 30°C Homo sapiens
219
-
 NAD+ mutant S346K/K347Y/K362H, pH 7.4, 30°C Homo sapiens
258
-
 NAD+ mutant E314A/S346K/K347Y/K362H, pH 7.4, 30°C Homo sapiens

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
7.4
-
 assay at Homo sapiens

Cofactor

Cofactor Comment Organism Structure
additional information nucleotide-binding site of c-NADP-ME, sequence comparisons, overview. A series of E314A-containing c-NADP-ME quadruple mutants are changed to NAD+-utilizing enzymes by abrogating NADP+ binding and increasing NAD+ binding Homo sapiens
NAD+ poor activity with NAD+ compared to NADP+ Homo sapiens
NADP+ Lys362 is the key residue contributing to binding the 2'-phosphate of NADP+ Homo sapiens

Ki Value [mM]

Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
0.73
-
 ATP mutants E314A and E314A/S346K, in presence of NAD+, pH 7.4, 30°C Homo sapiens
3.3
-
 ATP mutant E314A/S346K/K347Y/K362Q, in presence of NAD+, pH 7.4, 30°C Homo sapiens
3.9
-
 ATP mutant E314A/S346K/K347Y/K362Q, in presence of NADP+, pH 7.4, 30°C Homo sapiens
17.2
-
 ATP mutant E314A/S346K, in presence of NAPD+, pH 7.4, 30°C Homo sapiens
18.1
-
 ATP mutant E314A, in presence of NAPD+, pH 7.4, 30°C Homo sapiens
20.6
-
 ATP wild-type enzyme, in presence of NADP+, pH 7.4, 30°C Homo sapiens
23.2
-
 ATP wild-type enzyme, in presence of NAD+, pH 7.4, 30°C Homo sapiens

kcat/KM [mM/s]

kcat/KM Value [1/mMs-1] kcat/KM Value Maximum [1/mMs-1] Substrate Comment Organism Structure
2.8
-
 NAD+ wild-type enzyme, pH 7.4, 30°C Homo sapiens
36000
-
 NADP+ wild-type enzyme, pH 7.4, 30°C Homo sapiens