1.3.1.9: enoyl-[acyl-carrier-protein] reductase (NADH)
This is an abbreviated version!
For detailed information about enoyl-[acyl-carrier-protein] reductase (NADH), go to the full flat file.
Word Map on EC 1.3.1.9
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1.3.1.9
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tuberculosis
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mycobacterium
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triclosan
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falciparum
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plasmodium
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isoniazid
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medicine
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antitubercular
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mycolic
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antimycobacterial
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diazaborine
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triclosan-resistant
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pyrrolyl
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comsia
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surflex-docking
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inh-resistant
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drug development
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analysis
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pharmacology
- 1.3.1.9
- tuberculosis
- mycobacterium
- triclosan
- falciparum
- plasmodium
- isoniazid
- medicine
-
antitubercular
-
mycolic
-
antimycobacterial
- diazaborine
-
triclosan-resistant
-
pyrrolyl
-
comsia
-
surflex-docking
-
inh-resistant
- drug development
- analysis
- pharmacology
Reaction
Synonyms
2-trans enoyl-ACP-reductase, 2-trans enoyl-acyl carrier protein reductase, 2-trans-enoyl-ACP (CoA) reductase, 2-trans-enoyl-ACP reductase, 2-trans-enoyl-ACP(CoA) reductase, ACP reductase, BaENR, BMA0885, bsFabI, cold-shock induced protein 15, CSI15, EACP reductase, enoyl (acyl carrier protein) reductase, enoyl ACP reductase, enoyl acyl carrier protein reductase, enoyl acyl carrier protein reductase InhA, enoyl reductase, enoyl-ACP reductase, enoyl-ACP reductase I, enoyl-ACP reductase III, enoyl-ACP(CoA) reductase, enoyl-acyl carrier protein, enoyl-acyl carrier protein reductase, enoyl-acyl carrier protein reductase I, enoyl-reductase, enoyl-[acyl-carrier-protein] reductase, ENR, ENR1, ENR2, FabI, FabI-1, FabI-related enoyl-ACP reductase, FabI1, FabI2, FabK, Fabl1, Fabl2, FabMG, FabV, FAS-II enoyl reductase, FTT_0782, InhA, More, MtENR, MtInhA, NAD-dependent enoyl-ACP reductase, NADH-dependent enoyl reductase, NADH-dependent enoyl-ACP reductase, NADH-dependent enoyl-acyl carrier protein reductase, NADH-enoyl acyl carrier protein reductase, NADH-ENR, NADH-specific enoyl-ACP reductase, OsmC, PA2950, pfENR, reductase, enoyl-[acyl carrier protein], trans-enoyl-[acyl carrier protein] reductase, trans-enoyl-[acyl-carrier-protein] reductase, VEG241, vegetative protein 241, VF_0888, YP_4011
ECTree
1.3.1.9 enoyl-[acyl-carrier-protein] reductase (NADH)Advanced search results
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results (Engineering
Engineering on EC 1.3.1.9 - enoyl-[acyl-carrier-protein] reductase (NADH)
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PROTEIN VARIANTS 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
K244A
K244A/K245A
K244R
K245M
Y235A
Y235S
K244A
Y235A
F203L
A92V
no shift in melting temperature in presence of both triclosan and NADP+
I16T
I21V
I47T
M155A
-
vmax for NADH is similar to that of wild-type, the M155A Vmax for trans-2-dodecenoyl-CoA is around 64% of the wild-type rate
P193A
-
mutation inactivates the ability of InhA to turn over either NADH or trans-2-dodecenoyl-CoA
S94A
T266A
phosphoablative mutant with activity similar to wild-type enzyme
T266D
phosphomimetic mutant with strongly reduced activity (31.4% compared to wild-type enzyme), introduction of inhA_T266D fails to complement growth and mycolic acid defects of an inhA-thermosensitive Mycobacterium smegmatis strain, in a similar manner to what is observed following isoniazid treatment
T266E
phosphomimetic mutant strongly reduced activity (29.5% compared to wild-type enzyme), introduction of inhA_T266E fails to complement growth and mycolic acid defects of an inhA-thermosensitive Mycobacterium smegmatis strain, in a similar manner to what is observed following isoniazid treatment
V78A
the isoniazid-resistant mutation increases the structural stability of the protein with higher NADH binding affinity
W222A
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reduction in overall enoyl reductase activity, mutant shows an increased affinity for NADH
Y158A
decreased Kcat, unaffected Km for trans-2-dodecenoyl-CoA, lower Km for NADH
Y158F
Y158S
I16T
I21V
I47T
S94A
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similar to wild-type InhA, cross-linking of the isoniazid resistant mutant gives three bands on SDS-PAGE assigned to monomer, dimer, and tetrameric forms of the protein. The inhibition of the enzyme with the isoniazid-NAD adduct results in loss of the band assigned to tetramer. In contrast, cross-linking in the presence of saturating concentrations of NADH yields a lower amount of the tetramer upon SDS-PAGE
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T266A
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phosphoablative mutant with activity similar to wild-type enzyme
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T266D
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phosphomimetic mutant with strongly reduced activity (31.4% compared to wild-type enzyme), introduction of inhA_T266D fails to complement growth and mycolic acid defects of an inhA-thermosensitive Mycobacterium smegmatis strain, in a similar manner to what is observed following isoniazid treatment
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T266E
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phosphomimetic mutant strongly reduced activity (29.5% compared to wild-type enzyme), introduction of inhA_T266E fails to complement growth and mycolic acid defects of an inhA-thermosensitive Mycobacterium smegmatis strain, in a similar manner to what is observed following isoniazid treatment
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Y158F
-
mutation reduces the affinity of triclosan for the enzyme and results in noncompetitive inhibition
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I21V
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isoniazid-resistant mutant, loss of van der Waals interaction between NADH and the CD1 atom present in the valine residue leads to decrease of stability in binding of NADH in the active site of the protein
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S94A
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isoniazid-resistant mutant, alteration in the binding network involving a conserved water molecule and O9 atom of molecule of NADH leads to increase of the flexibility of the conserved water molecule and decrease of the affinity of NADH by protein
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V78A
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the isoniazid-resistant mutation increases the structural stability of the protein with higher NADH binding affinity
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Y158A
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decreased Kcat, unaffected Km for trans-2-dodecenoyl-CoA, lower Km for NADH
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Y158F
Y158S
A124V
mutantion results in resistance of Mycobacterium smegmatis to triclosan and significantly reduced affinity of the enzyme for triclosan
M161V
mutantion results in resistance of Mycobacterium smegmatis to triclosan and significantly reduced affinity of the enzyme for triclosan
A124V
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mutantion results in resistance of Mycobacterium smegmatis to triclosan and significantly reduced affinity of the enzyme for triclosan
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M161V
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mutantion results in resistance of Mycobacterium smegmatis to triclosan and significantly reduced affinity of the enzyme for triclosan
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A372M
mutation increases the affinity of the enzyme towards triclosan to almost double
A372V
mutation increases the affinity of the enzyme towards triclosan to almost double
G95V
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mutant enzyme retains normal activity with enoyl-[acyl-carrier-protein], but is highly resistant to triclosan
F204L
K266A
strain carrying the mutation is not viable at nonpermissive temperature. 1% of wild-type activity
Y260F
strain carrying the mutation is not viable at nonpermissive temperature. 5.7% of wild-type activity
F113A
restores fatty acid synthesis in an Escherichia coli fabI mutant strain to wild-type level
S50A
restores fatty acid synthesis in an Escherichia coli fabI mutant strain to wild-type level
T276A
restores fatty acid synthesis in an Escherichia coli fabI mutant strain to wild-type level
V246A
restores fatty acid synthesis in an Escherichia coli fabI mutant strain to wild-type level
Y226F
restores fatty acid synthesis in an Escherichia coli fabI mutant strain to wild-type level
Y53A
partly restores fatty acid synthesis in an Escherichia coli fabI mutant strain
Y53F
restores fatty acid synthesis in an Escherichia coli fabI mutant strain to wild-type level
T267A
the mutation results in a reduction in the kcat/KM value compared to the wild type enzyme
T267G
the mutation results in a 40fold reduction in the kcat/KM value compared to the wild type enzyme
T267V
the mutation results in a reduction in the kcat/KM value compared to the wild type enzyme
T267Y
the mutation results in a reduction in the kcat/KM value compared to the wild type enzyme
T276S
the mutation shows wild type catalytic efficiency but significantly reduces the affinity of diphenyl ether inhibitors for the enzyme (from 20fold to up to 100fold)
T267A
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the mutation results in a reduction in the kcat/KM value compared to the wild type enzyme
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T267G
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the mutation results in a 40fold reduction in the kcat/KM value compared to the wild type enzyme
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T267V
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the mutation results in a reduction in the kcat/KM value compared to the wild type enzyme
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T276S
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the mutation shows wild type catalytic efficiency but significantly reduces the affinity of diphenyl ether inhibitors for the enzyme (from 20fold to up to 100fold)
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additional information
K244A
mutation does not induce major structural alterations. 110fold decrease in kcat value
K244R
mutation does not induce major structural alterations. 950fold decrease in kcat value
K245M
mutation does not induce major structural alterations. 3fold increase in Km value for substrate dodecanoyl-CoA, 70fold decrease in kcat for substrate reduction
Y235A
mutation does not induce major structural alterations. 280fold decrease in kcat/Km ratio
Y235S
mutation does not induce major structural alterations. 280fold decrease in kcat/Km ratio
K244A
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mutation does not induce major structural alterations. 110fold decrease in kcat value
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Y235A
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mutation does not induce major structural alterations. 280fold decrease in kcat/Km ratio
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F203L
drug resistant mutant, probably due to an altered inhibitor-binding mode and a relatively more rigid binding site
I16T
mutation in the glycine-rich loop. Although very flexible, in the wild-type enzyme/NADH complex, the NADH molecule keeps its extended conformation firmly bound to the binding site of the enzyme. In the mutant complex, the NADH pyrophosphate moiety undergoes considerable conformational changes, reducing its interactions with its binding site and probably indicating the initial phase of ligand expulsion from the cavity
I21V
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isoniazid resistance mutant of Mycobacterium tuberculosis enoyl-[acyl-carrier-protein] reductase
I21V
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mutant, studied for understanding of the isoniazid drug resistance mechanism
I21V
isoniazid-resistant mutant, loss of van der Waals interaction between NADH and the CD1 atom present in the valine residue leads to decrease of stability in binding of NADH in the active site of the protein
I21V
InhA mutation that occur in isoniazid-resistant clinical isolates of Mycobacterium tuberculosis, show unimpaired inhibition by triclosan, with uncompetitive inhibition constant
I21V
mutation in the glycine-rich loop. Although very flexible, in the wild-type enzyme/NADH complex, the NADH molecule keeps its extended conformation firmly bound to the binding site of the enzyme. In the mutant complex, the NADH pyrophosphate moiety undergoes considerable conformational changes, reducing its interactions with its binding site and probably indicating the initial phase of ligand expulsion from the cavity
I21V
similar to wild-type InhA, cross-linking of the isoniazid resistant mutant gives three bands on SDS-PAGE assigned to monomer, dimer, and tetrameric forms of the protein. The inhibition of the enzyme with the isoniazid-NAD adduct results in loss of the band assigned to tetramer. In contrast, cross-linking in the presence of saturating concentrations of NADH yields a lower amount of the tetramer upon SDS-PAGE
I47T
-
mutant, studied for understanding of the isoniazid drug resistance mechanism
I47T
InhA mutation that occur in isoniazid-resistant clinical isolates of Mycobacterium tuberculosis, show unimpaired inhibition by triclosan, with uncompetitive inhibition constant
I47T
similar to wild-type InhA, cross-linking of the isoniazid resistant mutant gives three bands on SDS-PAGE assigned to monomer, dimer, and tetrameric forms of the protein. The inhibition of the enzyme with the isoniazid-NAD adduct results in loss of the band assigned to tetramer. In contrast, cross-linking in the presence of saturating concentrations of NADH yields a lower amount of the tetramer upon SDS-PAGE
S94A
-
mutant, studied for understanding of the isoniazid drug resistance mechanism
S94A
isoniazid-resistant mutant, alteration in the binding network involving a conserved water molecule and O9 atom of molecule of NADH leads to increase of the flexibility of the conserved water molecule and decrease of the affinity of NADH by protein
S94A
similar to wild-type InhA, cross-linking of the isoniazid resistant mutant gives three bands on SDS-PAGE assigned to monomer, dimer, and tetrameric forms of the protein. The inhibition of the enzyme with the isoniazid-NAD adduct results in loss of the band assigned to tetramer. In contrast, cross-linking in the presence of saturating concentrations of NADH yields a lower amount of the tetramer upon SDS-PAGE
S94A
-
similar activity compared to wild-type but a reduced NADH affinity, the affinity of S94A for is also decreased
Y158F
decreased Kcat, unaffected Km for trans-2-dodecenoyl-CoA, lower Km for NADH
Y158F
mutation reduces the affinity of triclosan for the enzyme and results in noncompetitive inhibition
Y158F
mutant retains only 1.8% of the wild-type kcat with a 2fold increase of the Km for octenoyl-CoA. Residue Y158 is essential for stereospecificity of protonation, the mutant accumulates a covalent adduct between crotonyl-CoA and NADH
Y158S
strong decrease in kcat to only 0.16% of wild-type activity
I16T
-
mutation in the glycine-rich loop. Although very flexible, in the wild-type enzyme/NADH complex, the NADH molecule keeps its extended conformation firmly bound to the binding site of the enzyme. In the mutant complex, the NADH pyrophosphate moiety undergoes considerable conformational changes, reducing its interactions with its binding site and probably indicating the initial phase of ligand expulsion from the cavity
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I21V
-
InhA mutation that occur in isoniazid-resistant clinical isolates of Mycobacterium tuberculosis, show unimpaired inhibition by triclosan, with uncompetitive inhibition constant
-
I21V
-
mutation in the glycine-rich loop. Although very flexible, in the wild-type enzyme/NADH complex, the NADH molecule keeps its extended conformation firmly bound to the binding site of the enzyme. In the mutant complex, the NADH pyrophosphate moiety undergoes considerable conformational changes, reducing its interactions with its binding site and probably indicating the initial phase of ligand expulsion from the cavity
-
I21V
-
similar to wild-type InhA, cross-linking of the isoniazid resistant mutant gives three bands on SDS-PAGE assigned to monomer, dimer, and tetrameric forms of the protein. The inhibition of the enzyme with the isoniazid-NAD adduct results in loss of the band assigned to tetramer. In contrast, cross-linking in the presence of saturating concentrations of NADH yields a lower amount of the tetramer upon SDS-PAGE
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I47T
-
InhA mutation that occur in isoniazid-resistant clinical isolates of Mycobacterium tuberculosis, show unimpaired inhibition by triclosan, with uncompetitive inhibition constant
-
I47T
-
similar to wild-type InhA, cross-linking of the isoniazid resistant mutant gives three bands on SDS-PAGE assigned to monomer, dimer, and tetrameric forms of the protein. The inhibition of the enzyme with the isoniazid-NAD adduct results in loss of the band assigned to tetramer. In contrast, cross-linking in the presence of saturating concentrations of NADH yields a lower amount of the tetramer upon SDS-PAGE
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Y158F
-
decreased Kcat, unaffected Km for trans-2-dodecenoyl-CoA, lower Km for NADH
-
Y158F
-
mutant retains only 1.8% of the wild-type kcat with a 2fold increase of the Km for octenoyl-CoA. Residue Y158 is essential for stereospecificity of protonation, the mutant accumulates a covalent adduct between crotonyl-CoA and NADH
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Y158S
-
strong decrease in kcat to only 0.16% of wild-type activity
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additional information
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the fabI knockout is as sensitive as the wild-type strain to the inhibitor triclosan
additional information
the fabI knockout is as sensitive as the wild-type strain to the inhibitor triclosan
additional information
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construction of tetracysteine-tagged enzyme variants carrying the tag at the N-terminus, C-terminus, or both N- and C-terminus. All the tetracysteine-tagged FabI enzymes have high enzyme activities while the enhanced green fluorescent protein-tagged FabI exhaustively loses the activity. The binding between 4',5'-bis(1,3,2-dithioarsolan-2-yl)fuorescein, i.e. FlAsH reagent and tetracysteine motif is stable against high pressure, high field strength, high temperature, and ultrasound. A capillary zone electrophoresis system equipped with a laser-induced fluorescence detector has a detection limit of 10-16 M for the labeled proteins
