1.1.1.42: isocitrate dehydrogenase (NADP+)

This is an abbreviated version, for detailed information about isocitrate dehydrogenase (NADP+), go to the full flat file.

Reaction

isocitrate
+
NADP+
=
2-oxoglutarate
+
CO2
+
NADPH
+
H+

Synonyms

AfIDH, CgIDH, cICDH, CtIDP1, CtIDP2, cytosolic isocitrate dehydrogenase 1, cytosolic NADP(+)-dependent isocitrate dehydrogenase, cytosolic NADP+-dependent isocitrate dehydrogenase, cytosolic NADP-dependent isocitrate dehydrogenase, cytosolic NADPH-dependent isocitrate dehydrogenase, DpIDH, EcIDH, ICD, ICD1, ICD2, ICDH, ICDH-1, IDH, IDH1, IDH2, IDH3, IDHP, IDP, IDP1, IDP2, IDP3, IDPA, IDPc, IDPm, isocitrate dehydrogenase, isocitrate dehydrogenase (NADP), isocitrate dehydrogenase (NADP-dependent), isocitrate dehydrogenase (nicotinamide adenine dinucleotide phosphate), isocitrate dehydrogenase 1, isocitrate dehydrogenase 2, isocitrate dehydrogenase-1, isocytrate deyhdrogenase, mICDH, mitochondrial NADP+-dependent isocitrate dehydrogenase, NAD+-dependent isocitrate dehydrogenase, NADP isocitric dehydrogenase, NADP+-dependent Ds-threo-isocitrate dehydrogenase, NADP+-dependent Ds-threo-isocitrate:NADP+ oxidoreductase, NADP+-dependent IDH, NADP+-dependent isocitrate dehydrogenase, NADP+-ICDH, NADP+-IDH, NADP+-isocitrate dehydrogenase, NADP+-linked isocitrate dehydrogenase, NADP+-specific ICDH, NADP+-specific isocitrate dehydrogenase, NADP-dependent IDH, NADP-dependent isocitrate dehydrogenase, NADP-dependent isocitric dehydrogenase, NADP-ICDH, NADP-IDH, NADP-IDH Idp1p, NADP-isocitrate dehydrogenase, NADP-linked isocitrate dehydrogenase, NADP-specific isocitrate dehydrogenase, NADPH-dependent isocitrate dehydrogenase, oxalosuccinate decarboxylase, oxalsuccinic decarboxylase, perICDH, PS-NADP-IDH, TaIDH, TM1148

ECTree

     1 Oxidoreductases
         1.1 Acting on the CH-OH group of donors
             1.1.1 With NAD+ or NADP+ as acceptor
                1.1.1.42 isocitrate dehydrogenase (NADP+)

Engineering

Engineering on EC 1.1.1.42 - isocitrate dehydrogenase (NADP+)

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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
A325P/G326S
-
50% inactivation after 10 min at 91.3C as compared to 87.5C for wild-type enzyme
A336F
-
50% inactivation after 10 min at 74C as compared to 87.5C or wild-type enzyme
I321L
-
50% inactivation after 10 min at 88.9C as compared to 87.5C for wild-type enzyme
Y309I/I310L
-
50% inactivation after 10 min at 88.4C as compared to 87.5C for wild-type enzyme
Y309I/I310L/I321L/A325P/G326S
-
50% inactivation after 10 min at 90C as compared to 87.5C for wild-type enzyme
C201M
-
higher affinity for NAD+ than for NADP+
C201N
-
higher affinity for NAD+ than for NADP+
C201V
-
higher affinity for NAD+ than for NADP+
S113E
-
affinity for isopropylmalate is 37-fold compared to wild-type
R291S
Q8X277
involved in coenzyme specificity
R291S/K343D/Y344I/V350A/Y390P
Q8X277
switch in coenzyme specificity from NADP+ to NAD+
R291S/K343D/Y344I/Y390P
Q8X277
involved in coenzyme specificity
R291S/K343D/Y390P
Q8X277
involved in coenzyme specificity
R291S/Y390P
Q8X277
involved in coenzyme specificity
G123R
-
site-directed mutagenesis, mutation is located in the catalytic domain, the mutant shows reduced activity compared to the wild-type enzyme
R132V
-
naturally occuring IDH1 mutation
R172K
-
IDH2 R172 mutation causes production and accumulation of 2-hydroxyglutarate in acute myelogenous leukemia cells
R172X
-
naturally occuring mutations of IDH2 in metastatic brain tumors
D375N
-
15fold increase in KM-value for NADP+, marked decrease of Vmax-value
H309F
-
site-directed mutagenesis, inactive mutant, poor cofactor binding, altered secondary structure
H309Q
-
site-directed mutagenesis, inactive mutant, poor cofactor binding, altered secondary structure
H315Q
-
site-directed mutagenesis, 40fold increased Km for NADP+ compared to the wild-type enzyme
H319Q
-
site-directed mutagenesis, cofactor binding and kinetics similar to the wild-type enzyme, slightly reduced activity
K212Q
-
site-directed mutagenesis, highly decreased activity in both reaction directions compared to the wild-type enzyme, altered pH-dependency of the activity
K212R
-
site-directed mutagenesis, highly decreased activity in both reaction directions compared to the wild-type enzyme, altered pH-dependency of the activity
K212Y
-
site-directed mutagenesis, highly decreased activity in both reaction directions compared to the wild-type enzyme, altered pH-dependency of the activity
K260Q
-
28fold increase in KM-value for NADP+, marked decrease of Vmax-value
K321Q
-
site-directed mutagenesis, kinetics are similar to the wild-type enzyme
K374Q
-
little change in kinetic parameters
N328D
-
36% decrease in vmax-value compared to wild-type
N328S
-
slight decrease in vmax-value compared to wild-type
N97A
-
site-directed mutagenesis, decreased Vmax compared to the wild-type enzyme, slightly affected Km values, but increased pKa of the ionizable metal-liganded hydroxyl of enzyme-bound isocitrate compared to the wild-type enzyme
N97D
-
site-directed mutagenesis, highly decreased Vmax compared to the wild-type enzyme
R132X
-
mutation of an arginine residue in pig mitochondrial IDH2 equivalent to R132 in human IDH1 causes a dramatic increase in Km for isocitrate by a factor of 165, with minimal effect on Vmax
R314Q
-
site-directed mutagenesis, 10fold increased Km for NADP+ compared to the wild-type enzyme
R323Q
-
site-directed mutagenesis, kinetics are similar to the wild-type enzyme
R83K
-
slight decrease in vmax-value compared to wild-type
R83Q
-
slight decrease in vmax-value compared to wild-type
S95A
-
site-directed mutagenesis, decreased Vmax, and increased Km for isocitrate and Mn2+ compared to the wild-type enzyme
S95D
-
site-directed mutagenesis, highly decreased Vmax compared to the wild-type enzyme
T311A
-
slight decrease in vmax-value compared to wild-type
T311N
-
vmax-value is less than 1% of the value of wild-type
T311S
-
large increase in vmax-value compared to wild-type
T373A
-
reduction of Vmax-value to 1% of wild-type
T373S
-
little change in kinetic parameters
T373V
-
reduction of Vmax-value to 20% of wild-type
T78A
-
site-directed mutagenesis, decreased Vmax, and increased Km for isocitrate and Mn2+ compared to the wild-type enzyme
T78D
-
site-directed mutagenesis, decreased Vmax compared to the wild-type enzyme
Y140E
-
site-directed mutagenesis, highly decreased activity in both reaction directions compared to the wild-type enzyme, unaltered Km for isocitrate and NADP+
Y140F
-
site-directed mutagenesis, highly decreased activity in both reaction directions compared to the wild-type enzyme, unaltered Km for isocitrate and NADP+
Y140K
-
site-directed mutagenesis, highly decreased activity in both reaction directions compared to the wild-type enzyme, unaltered Km for isocitrate and NADP+
Y140T
-
site-directed mutagenesis, highly decreased activity in both reaction directions compared to the wild-type enzyme, unaltered Km for isocitrate and NADP+, highly increased activation by added exogenous acetic acid and phenol compared to the wild-type enzyme
Y316F
-
site-directed mutagenesis, kinetics are similar to the wild-type enzyme
Y316L
-
site-directed mutagenesis, 4fold increased Km for NADP+ compared to the wild-type enzyme
D389N
-
reduction in apparent melting temperature by 21.8C compared to wild-type
F205M
-
reduction in apparent melting temperature by 3.5C compared to wild-type
R186M
-
no change in apparent melting temperature compared to wild-type
additional information