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Information on EC 1.1.1.100 - 3-oxoacyl-[acyl-carrier-protein] reductase and Organism(s) Plasmodium falciparum and UniProt Accession Q965D6
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1.1.1.100 3-oxoacyl-[acyl-carrier-protein] reductaseIUBMB Comments
Exhibits a marked preference for acyl-carrier-protein derivatives over CoA derivatives as substrates.
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Word Map
- 1.1.1.100
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enoyl
- drug development
-
transacylase
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3-oxoacyl-acyl-carrier-protein
-
dehydrase
- enoyl-acp
-
3-oxoacyl-acyl
- acyl-acps
-
beta-hydroxyacyl-acp
- fas-ii
- 4'-phosphopantetheine
- synthesis
The taxonomic range for the selected organisms is: Plasmodium falciparum
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Reaction Schemes
Synonyms
beta-ketoacyl reductase, fabg1, fabg4, beta-ketoacyl-acp reductase, 3-oxoacyl-acp reductase, fabg3, beta-ketoacyl-acyl carrier protein reductase, 3-ketoacyl-acp reductase, fabg2, oar1p, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
3-ketoacyl acyl carrier protein reductase
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3-ketoacyl-acyl carrier protein reductase
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3-oxoacyl-[ACP]reductase
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beta-ketoacyl acyl carrier protein (ACP) reductase
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beta-ketoacyl reductase
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beta-ketoacyl thioester reductase
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beta-ketoacyl-ACP reductase
beta-ketoacyl-acyl carrier protein reductase
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beta-ketoacyl-[acyl-carrier protein] (ACP) reductase
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FabG
NADPH-specific 3-oxoacyl-[acylcarrier protein]reductase
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reductase, 3-oxoacyl-[acyl carrier protein]
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beta-ketoacyl-ACP reductase
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
a (3R)-3-hydroxyacyl-[acyl-carrier protein] + NADP+ = a 3-oxoacyl-[acyl-carrier protein] + NADPH + H+
a (3R)-3-hydroxyacyl-[acyl-carrier protein] + NADP+ = a 3-oxoacyl-[acyl-carrier protein] + NADPH + H+
cofactor and substrate binding kinetics, allosteric regulation mechanism, overview
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a (3R)-3-hydroxyacyl-[acyl-carrier protein] + NADP+ = a 3-oxoacyl-[acyl-carrier protein] + NADPH + H+
ordered bi bi kinetic mechanism, [acyl-carrier protein] recognition mechanism
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
redox reaction
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oxidation
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reduction
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PATHWAY SOURCE
PATHWAYS
BRENDA
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-, -, -, -, -, -, -, -, -, -, -, -, -, -, -, -, -, -, -, -, -
SYSTEMATIC NAME
IUBMB Comments
(3R)-3-hydroxyacyl-[acyl-carrier protein]:NADP+ oxidoreductase
Exhibits a marked preference for acyl-carrier-protein derivatives over CoA derivatives as substrates.
CAS REGISTRY NUMBER
COMMENTARY
37250-34-3
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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
acetoacetyl-CoA + NADPH + H+
D-beta-hydroxybutyryl-CoA + NADP+
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-
-
?
3-oxoacyl-[acyl-carrier protein] + NADPH
(3R)-3-hydroxyacyl-[acyl-carrier protein] + NADP+
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-
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-
?
acetoacetyl-CoA + NADPH
? + NADP+
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wild-type shows less activity with acetoacetyl-CoA than with acetoacetyl-[acyl-carrier protein]
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-
?
acetoacetyl-[acyl-carrier protein] + NADPH
D-beta-hydroxybutyryl-[acyl-carrier protein] + NADP+
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Arg187 and Arg230 are critical residues for the FabG-acyl-carrier protein interactions, significance of the positively charged/hydrophobic patch located adjacent to the active site cavities of FabG for interactions with acyl carrier protein
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?
3-oxoacyl-[acyl-carrier protein] + NADPH
3-hydroxyacyl-[acyl-carrier protein] + NADP+
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r
3-oxoacyl-[acyl-carrier protein] + NADPH
3-hydroxyacyl-[acyl-carrier protein] + NADP+
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cooperative transitions in the enzyme due to cofactor and [acyl-carrier-protein] binding
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r
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
3-oxoacyl-[acyl-carrier protein] + NADPH
3-hydroxyacyl-[acyl-carrier protein] + NADP+
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-
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r
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
NADPH
exhibits negative cooperativity for its interaction with the enzyme
NADP+
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cooperative transitions in the enzyme due to cofactor and [acyl-carrier-protein] binding, cooperative cofactor binding
NADPH
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cooperative transitions in the enzyme due to cofactor and [acyl-carrier-protein] binding, cooperative allosteric cofactor binding in presence of [acyl-carrier-protein]
NADPH
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3fold enhancement in acyl-carrier protein binding to wild-type in the presence of NADPH
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
the enzyme activity is maximal at a ionic strength of 325 mM
additional information
-
the enzyme activity is maximal at a ionic strength of 325 mM
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
acyl-carrier protein
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inhibition of wild-type with increasing concentrations
bromochlorophen
an anthelmintic agent, over 75% inhibition at 0.02 mM, IC50: 0.0154 mM
di-resorcinol sulfide
over 75% inhibition at 0.02 mM, IC50: 0.0038 mM
Guanidinium chloride
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FabG is fully unfolded at 4 M, approximately 90% of the enzyme activity can be recovered on dialyzing the denaturant. In presence of NADPH, there is no stabilization of FabG in case of equilibrium unfolding with guanidinium chloride
Hexachlorophene
an anthelmintic and antimicrobial agent, over 75% inhibition at 0.02 mM, IC50: 0.002 mM
Urea
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FabG is fully unfolded at 6 M, approximately 90% of the enzyme activity can be recovered on dialyzing the denaturant. Two states in the reversible unfolding process of FabG in presence of NADPH, one is an activity-enhanced state and the other, an inactive state in case of equilibrium unfolding with urea
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
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affinity of acyl-carrier protein for FabG is increased by 3fold in the presence of 1 M urea
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
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cooperativity kinetics, binding constants of substrates and cofactors
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additional information
additional information
kinetic analysis of the recombinant enzyme, kinetic mechanism
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additional information
additional information
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kinetic analysis of the recombinant enzyme, kinetic mechanism
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0154
bromochlorophen
Plasmodium falciparum
an anthelmintic agent, over 75% inhibition at 0.02 mM, IC50: 0.0154 mM
0.0038
di-resorcinol sulfide
Plasmodium falciparum
over 75% inhibition at 0.02 mM, IC50: 0.0038 mM
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
2
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mutant R187E/R230E, acyl-carrier protein-dependent spectroscopic assay
3
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mutant R187A/R230A, acyl-carrier protein-dependent spectroscopic assay
42.6
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mutant R187E/R230E, acyl-carrier protein-independent spectroscopic assay
45.6
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mutant R187A/R230A, acyl-carrier protein-independent spectroscopic assay
54.2
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mutant R230E, acyl-carrier protein-independent spectroscopic assay
54.5
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mutant R187E, acyl-carrier protein-independent spectroscopic assay
55.3
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mutant R230A, acyl-carrier protein-independent spectroscopic assay
57.9
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mutant R187A, acyl-carrier protein-independent spectroscopic assay
59.8
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6.8
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). Q965D6_PLAFA
301
0
33320
TrEMBL
Secretory Pathway (Reliability: 5)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
tetramer
tetramer
crystal structure and ultrafiltration, quarternary structure analysis, monomer interactions, conformations in absence and presence of cofactor NADP+
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
purified recombinant enzyme, vapour diffusion method, 10 mg/ml protein in 20 mM HEPES, pH 6.8, 0.5 M NaCl, 1 mM DTT, and 0.5 mM EDTA, is mixed with an equal volume of reservoir solution containing 0.1 M MES, pH 6.0, 35% v/v 2-methyl-2,4-pentanediol, and 0.2 M LiSO4, equilibration against 1 ml of mother liquor, room temperature, 6 weeks, X-ray diffraction structure determination and analysis at 1.9 A resolution
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
R187A
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kinetic constants (Km and acyl-carrier protein-independent specific activities) remain largely unchanged with respect to wild-type. Exhibits very poor activity in the acyl-carrier protein-dependent spectroscopic assay. No inhibition by increasing concentrations of acyl-carrier protein. 3fold decreased affinity binding to acyl-carrier protein with respect to wild-type
R187A/R230A
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kinetic constants (Km and acyl-carrier protein-independent specific activities) remain largely unchanged with respect to wild-type. Exhibits very poor activity in the acyl-carrier protein-dependent spectroscopic assay. 5fold decreased affinity binding to acyl-carrier protein with respect to wild-type
R187E
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kinetic constants (Km and acyl-carrier protein-independent specific activities) remain largely unchanged with respect to wild-type. Exhibits very poor activity in the acyl-carrier protein-dependent spectroscopic assay. No inhibition by increasing concentrations of acyl-carrier protein. 4fold decreased affinity binding to acyl-carrier protein with respect to wild-type
R187E/R230E
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kinetic constants (Km and acyl-carrier protein-independent specific activities) remain largely unchanged with respect to wild-type. Exhibits very poor activity in the acyl-carrier protein-dependent spectroscopic assay. 80fold decreased affinity binding to acyl-carrier protein with respect to wild-type
R187K
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no decreased affinity binding to acyl-carrier protein with respect to wild-type
R230A
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kinetic constants (Km and acyl-carrier protein-independent specific activities) remain largely unchanged with respect to wild-type. Exhibits very poor activity in the acyl-carrier protein-dependent spectroscopic assay. No inhibition by increasing concentrations of acyl-carrier protein. 5fold decreased affinity binding to acyl-carrier protein with respect to wild-type
R230E
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kinetic constants (Km and acyl-carrier protein-independent specific activities) remain largely unchanged with respect to wild-type. Exhibits very poor activity in the acyl-carrier protein-dependent spectroscopic assay. No inhibition by increasing concentrations of acyl-carrier protein. 41fold decreased affinity binding to acyl-carrier protein with respect to wild-type
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
the purified recombinant enzyme is stable at room temperature at concentrations above 0.2 mg/ml, but unstable at 0.01 mg/ml
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant C-terminally His-tagged enzyme from Escherichia coli strain BL21(DE3) by nickel affinity chromatography
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recombinant His-tagged enzyme from Escherichia coli strain BL21(DE3) solubilized from inclusion bodies and refolded is further purified by nickel affinity chromatography
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recombinant His10-tagged enzyme from Escherichia coli by nickel affinity chromatography and gel filtration
wild-type and mutants purified to homogeneity using an Ni2+-nitrilotriacetic acid affinity column
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
gene fabG, DNA and amino acid sequence determination and analysis, expression of C-terminally His-tagged enzyme in Escherichia coli strain BL21(DE3)
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gene fabG, DNA and amino acid sequence determination and analysis, expression of His10-tagged enzyme in Escherichia coli
into pET-28a vector and expressed in Escherichia coli BL21 (DE3) codon plus
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overexpression of His-tagged enzyme in Escherichia coli strain BL21(DE3) in inclusion bodies
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wild-type and mutants cloned into the pET-28a(+) vector and expressed in Escherichia coli BL21 (DE3) codon plus
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RENATURED/Commentary
ORGANISM
UNIPROT
LITERATURE
solubilization of overexpressed recombinant His-tagged enzyme from Escherichia coli strain BL21(DE3) inclusion bodies by 8 M urea, and refolding by dialysis, cation exchange chromatography, and dilution in presence of 0.001 mM NADPH in 20 mM sodium acetate, pH 5.3, 10% glycerol, and 0.05% Tween 20, the refolded enzyme shows 90-95% of soluble enzyme activity
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study on guanidinium chloride-induced isothermal and thermal denaturation. Folding/unfolding is completely reversible and a two-state process. Conformational stability, i.e. DELTAGS, and the DELTACP value for the protein unfolding, are 22.68 kcal/mole and 5.83 kcal/(mole K)
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
drug development
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the enzyme has no isoforms and thus is a good target for inhibitor design
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Pillai, S.; Rajagopal, C.; Kapoor, M.; Kumar, G.; Gupta, A.; Surolia, N.
Functional characterization of beta-ketoacyl-ACP reductase (FabG) from Plasmodium falciparum
Biochem. Biophys. Res. Commun.
303
387-392
2003
Plasmodium falciparum (Q965D6), Plasmodium falciparum
Wickramasinghe, S.R.; Inglis, K.A.; Urch, J.E.; Mueller, S.; van Aalten, D.M.; Fairlamb, A.H.
Kinetic, inhibition and structural studies on 3-oxoacyl-ACP reductase from Plasmodium falciparum, a key enzyme in fatty acid biosynthesis
Biochem. J.
393
447-457
2006
Plasmodium falciparum (Q86RB1), Plasmodium falciparum
Karmodiya, K.; Surolia, N.
Analyses of co-operative transitions in Plasmodium falciparum beta-ketoacyl acyl carrier protein reductase upon co-factor and acyl carrier protein binding
FEBS J.
273
4093-4103
2006
Plasmodium falciparum
Karmodiya, K.; Srivastav, R.K.; Surolia, N.
Production and purification of refolded recombinant Plasmodium falciparum beta-ketoacyl-ACP reductase from inclusion bodies
Protein Expr. Purif.
42
131-136
2005
Plasmodium falciparum
Karmodiya, K.; Sajad, S.; Sinha, S.; Maity, K.; Suguna, K.; Surolia, N.
Conformational stability and thermodynamic characterization of homotetrameric Plasmodium falciparum beta-ketoacyl-ACP reductase
IUBMB Life
59
441-449
2007
Plasmodium falciparum
Karmodiya, K.; Modak, R.; Sahoo, N.; Sajad, S.; Surolia, N.
Deciphering the key residues in Plasmodium falciparum beta-ketoacyl acyl carrier protein reductase responsible for interactions with Plasmodium falciparum acyl carrier protein
FEBS J.
275
4756-4766
2008
Plasmodium falciparum
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