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Information on EC 1.3.1.104 - enoyl-[acyl-carrier-protein] reductase (NADPH)
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1.3.1.104 enoyl-[acyl-carrier-protein] reductase (NADPH)IUBMB Comments
The enzyme completes each cycle of fatty acid elongation by catalysing the stereospecific reduction of the double bond at position 2 of a growing fatty acid chain, while linked to the acyl-carrier protein, in an NADPH-dependent manner. This entry stands for enzymes whose stereo-specificity with respect to NADP+ is not known. [cf. EC 1.3.1.39 enoyl-[acyl-carrier-protein] reductase (NADPH, Re-specific), EC 1.3.1.10, enoyl-[acyl-carrier-protein] reductase (NADPH, Si-specific) and EC 1.3.1.9, enoyl-[acyl-carrier-protein] reductase (NADH)].
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The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
Reaction Schemes
Synonyms
enoyl-ACP reductase, enoyl-acyl carrier protein reductase, enoyl-[acyl carrier protein] (reduced nicotinamide adenine dinucleotide phosphate) reductase, ENR, ETR1, FabI, FabL, Fabl2, JamJ, NADPH 2-enoyl Co A reductase, 
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
enoyl-ACP reductase
enoyl-[acyl carrier protein] (reduced nicotinamide adenine dinucleotide phosphate) reductase
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-
-
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FabI
FabL
NADPH 2-enoyl Co A reductase
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-
-
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NWMN_0881
YgaA
enoyl-ACP reductase
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-
-
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FabL
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
acyl-[acyl-carrier protein] + NADP+ = trans-2,3-dehydroacyl-[acyl-carrier protein] + NADPH + H+
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-
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PATHWAY SOURCE
PATHWAYS
BRENDA
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SYSTEMATIC NAME
IUBMB Comments
acyl-[acyl-carrier protein]:NADP+ oxidoreductase
The enzyme completes each cycle of fatty acid elongation by catalysing the stereospecific reduction of the double bond at position 2 of a growing fatty acid chain, while linked to the acyl-carrier protein, in an NADPH-dependent manner. This entry stands for enzymes whose stereo-specificity with respect to NADP+ is not known. [cf. EC 1.3.1.39 enoyl-[acyl-carrier-protein] reductase (NADPH, Re-specific), EC 1.3.1.10, enoyl-[acyl-carrier-protein] reductase (NADPH, Si-specific) and EC 1.3.1.9, enoyl-[acyl-carrier-protein] reductase (NADH)].
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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
crotonyl-N-acetylcysteamine + NADPH + H+
butyryl-N-acetylcysteamine + NADP+
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-
-
?
gama-chloro-beta-methylcrotonyl-[acyl-carrier-protein] + NADPH + H+
gama-chloro-beta-methylbutanoyl-[acyl-carrier-protein] + NADP+
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-
-
?
additional information
?
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the enzyme shows no 7-alpha hydroxysteroid dehydrogenase activity when tested with cholic acid substrate and NADH and NADPH cofactors. The purified protein does not utilize NADH as a cofactor when tested with crotonyl-[CoA] as substrate
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-
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crotonyl-[acyl-carrier-protein] + NADPH + H+
butyryl-[acyl-carrier-protein] + NADP+
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-
-
?
crotonyl-[acyl-carrier-protein] + NADPH + H+
butyryl-[acyl-carrier-protein] + NADP+
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-
-
?
crotonyl-[acyl-carrier-protein] + NADPH + H+
butyryl-[acyl-carrier-protein] + NADP+
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-
-
?
crotonyl-[acyl-carrier-protein] + NADPH + H+
butyryl-[acyl-carrier-protein] + NADP+
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-
-
?
crotonyl-[acyl-carrier-protein] + NADPH + H+
butyryl-[acyl-carrier-protein] + NADP+
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-
-
-
?
trans-2-octenoyl-N-acetylcysteamine + NADPH + H+
octanoyl-N-acetylcysteamine + NADP+
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-
-
?
trans-2-octenoyl-N-acetylcysteamine + NADPH + H+
octanoyl-N-acetylcysteamine + NADP+
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-
-
?
trans-2-octenoyl-N-acetylcysteamine + NADPH + H+
octanoyl-N-acetylcysteamine + NADP+
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-
-
?
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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
crotonyl-[acyl-carrier-protein] + NADPH + H+
butyryl-[acyl-carrier-protein] + NADP+
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-
-
-
?
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
NADPH
exhibits specific and positive cooperative binding of NADPH. The cofactor concentration that yields 50% of the maximal rate is 65 microM
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
AFN-1252
antibiotic AFN-1252, i.e. (2E)-N-methyl-N-[(3-methyl-1-benzofuran-2-yl)methyl]-3-(7-oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)prop-2-enamide, only binds to the NADPH form of FabI
triclosan
enzyme is reversibly inhibited by triclosan, but does not form a stable ternary complex
triclosan
the introduction of a plasmid expressing the enzyme gene leads to triclosan resistance
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
metabolism
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the whole reaction involves the formation of the covalent ene adduct and the proton transfer from Tyr79 to the substrate. In the first step the hydride of NADPH easily transfers to crotonyl-CoA to generate the substrate carbanion if the hydroxyl of Tyr79 forms a hydrogen bond chain with Ser70 and crystal water molecules. Then, the carbanion and NADP+ form a stable covalent ene adduct. The formation of the ene adduct follows the Michael addition mechanism rather than the electrocyclic ene reactions. The final electrophilic attack of the Tyr79 proton on C8 of the substrate affords the product of acyl thioester. The key crystal water molecules do not directly participate in the catalytic reactions, but they play a role in maintaining the relative stability of the substrate to NADPH
physiological function
physiological function
expression complements the Escherichia coli fabI temperature-sensitive mutant
physiological function
expression of isoform FabL complements the temperature-sensitive fabI defect in Escherichia coli and confers complete triclosan resistance. Knockouts of the FabL gene in Bacillus subtilis are viable, but double knockouts of isoforms FabI and FabL are not obtained. The ygaA knockout is 250fold more sensitive to triclosan than wild-type
physiological function
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expression of isoform FabL complements the temperature-sensitive fabI defect in Escherichia coli and confers complete triclosan resistance. Knockouts of the FabL gene in Bacillus subtilis are viable, but double knockouts of isoforms FabI and FabL are not obtained. The ygaA knockout is 250fold more sensitive to triclosan than wild-type
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Show AA Sequence and Transmembrane Helices (624 entries)
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Please use the AA Sequence and Transmembrane Helices Search for a specific query.
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PDB
SCOP
CATH
UNIPROT
ORGANISM
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
both free form and complexed with NADP+ and inhibitor triclosan, to 2.2 and 1.8 A resolution, respectively. The substrate-binding region in the apo-FabL structure is found in the open form. In addition, the beta4-alpha5 and beta5-alpha7 regions, which include the catalytic residues as well as the cofactor binding residues, get collapsed into the pocket. These differences result in a tetrameric arrangement totally different from NADH-dependent isoform FabI
to 2.5 A resolution. Hexagonal space group P622, with unit-cell parameters a = b = 139.56, c = 62.75 A , alpha = beta = 90, gamma = 120°
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
A95V
F204S
G23S
mutation increases the resistance of Staphylococcus aureus to triclosan by an order of magnitude
I193S
no shift in melting temperature in presence of both triclosan and NADP+
M99T
Y147H
mutant is resistant to antibiotic AFN-1252 and to triclosan, about 5% of wild-type catalytic activity. A strain expressing Y147H has a pronounced growth defect that is rescued by exogenous fatty acid supplementation
A95V
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about 15% of wild-type activtiy, no inhibition by triclosan and no shift in melting temperature in presence of both triclosan and NADP+
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F204S
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no shift in melting temperature in presence of both triclosan and NADP+
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I193S
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no shift in melting temperature in presence of both triclosan and NADP+
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M99T
Y147H
-
mutant is resistant to antibiotic AFN-1252 and to triclosan, about 5% of wild-type catalytic activity. A strain expressing Y147H has a pronounced growth defect that is rescued by exogenous fatty acid supplementation
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additional information
replacement of amino acids 55-66 by CurF enoyl reductase cyclopropanase loop leads to gain-of-function activity as a cyclopropanase. With substrate 3-chloromethyl-crotonyl-[acyl-carrier-protein], the formation of both the reduced product and also the cyclopropanated productis detected at levels of about one-quarter of the total product
A95V
about 15% of wild-type activtiy, no inhibition by triclosan and no shift in melting temperature in presence of both triclosan and NADP+
F204S
no shift in melting temperature in presence of both triclosan and NADP+
M99T
mutant is resistant to antibiotic AFN-1252 but susceptible to triclosan. Strains expressing M99T exhibit normal growth, and the biochemical properties of the purified protein are indistinguishable from those of FabI
M99T
mutant shows a similar shift in melting temperature in presence of both triclosan and NADP+ as wild-type
M99T
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mutant shows a similar shift in melting temperature in presence of both triclosan and NADP+ as wild-type
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M99T
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mutant is resistant to antibiotic AFN-1252 but susceptible to triclosan. Strains expressing M99T exhibit normal growth, and the biochemical properties of the purified protein are indistinguishable from those of FabI
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TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
58.8
wild-type, melting temperature in presence of both triclosan and NADP+. Neither triclosan nor NADP+ alone increases the Tm value
60.2
mutant M99T, melting temperature in presence of both triclosan and NADP+
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GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
no enzymatic activity is observed in 100 mM sodium citrate buffer regardless of the pH
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression in Escherichia coli
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
analysis
analysis
development of a simple thermal shift assay, which does not use ACP-linked substrates, to determine the binding ability of triclosan to the enzyme's active site
analysis
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development of a simple thermal shift assay, which does not use ACP-linked substrates, to determine the binding ability of triclosan to the enzyme's active site
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Heath, R.J.; Li, J.; Roland, G.E.; Rock, C.O.
Inhibition of the Staphylococcus aureus NADPH-dependent enoyl-acyl carrier protein reductase by triclosan and hexachlorophene
J. Biol. Chem.
275
4654-4659
2000
Staphylococcus aureus (Q9RMI3)
brenda
Heath, R.J.; Su, N.; Murphy, C.K.; Rock, C.O.
The enoyl-[acyl-carrier-protein] reductases FabI and FabL from Bacillus subtilis
J. Biol. Chem.
275
40128-40133
2000
Bacillus subtilis (P71079), Bacillus subtilis 168 (P71079)
brenda
Kim, K.H.; Park, J.K.; Ha, B.H.; Moon, J.H.; Kim, E.E.
Crystallization and preliminary X-ray crystallographic analysis of enoyl-ACP reductase III (FabL) from Bacillus subtilis
Acta Crystallogr. Sect. F
63
246-248
2007
Bacillus subtilis (P71079), Bacillus subtilis 168 (P71079)
brenda
Kim, K.H.; Ha, B.H.; Kim, S.J.; Hong, S.K.; Hwang, K.Y.; Kim, E.E.
Crystal structures of enoyl-ACP reductases I (FabI) and III (FabL) from B. subtilis
J. Mol. Biol.
406
403-415
2011
Bacillus subtilis (P71079), Bacillus subtilis 168 (P71079)
brenda
Yao, J.; Maxwell, J.B.; Rock, C.O.
Resistance to AFN-1252 arises from missense mutations in Staphylococcus aureus enoyl-acyl carrier protein reductase (FabI)
J. Biol. Chem.
288
36261-36271
2013
Staphylococcus aureus (Q9RMI3), Staphylococcus aureus RN4220 (Q9RMI3)
brenda
Demissie, R.D.; Kabre, P.; Tuntland, M.L.; Fung, L.W.
An efficient and economical assay to screen for triclosan binding to FabI
J. Biomol. Screen.
21
391-398
2016
Staphylococcus aureus (A0A0H3K7V7), Staphylococcus aureus Newman (A0A0H3K7V7)
brenda
Khare, D.; Hale, W.; Tripathi, A.; Gu, L.; Sherman, D.; Gerwick, W.; Hakansson, K.; Smith, J.
Structural basis for cyclopropanation by a unique enoyl-acyl carrier protein reductase
Structure
23
2213-2223
2015
Lyngbya majuscula (Q6E7K0)
brenda
Ling, B.; Li, H.; Yan, L.; Liu, R.; Liu, Y.
Conversion mechanism of enoyl thioesters into acyl thioesters catalyzed by 2-enoyl-thioester reductases from Candida tropicalis
Phys. Chem. Chem. Phys.
21
10105-10113
2019
Candida tropicalis
brenda
Demissie, R.; Kabre, P.; Fung, L.
Nonactive-site mutations in S. aureus FabI that induce triclosan resistance
ACS Omega
5
23175-23183
2020
Staphylococcus aureus
brenda
Khan, R.; Zeb, A.; Roy, N.; Thapa Magar, R.; Kim, H.J.; Lee, K.W.; Lee, S.W.
Biochemical and structural basis of triclosan resistance in a novel enoyl-acyl carrier protein reductase
Antimicrob. Agents Chemother.
62
e00648-18
2018
uncultured bacterium pBF1
brenda
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Release 2023.1 (January 2023)
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