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EC Tree
The taxonomic range for the selected organisms is: Escherichia coli The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
Synonyms
ics, isochorismate synthase, amonabactin, salicylate synthase, isochorismate synthase 1, eds16, atics1, isochorismate hydroxymutase, menaquinone-specific isochorismate synthase, atics2,
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menaquinone-specific isochorismate synthase
-
isochorismate mutase
-
-
-
-
Isochorismic synthase
-
-
-
-
Synthase, isochorismate
-
-
-
-
ICS
-
-
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chorismate = isochorismate
chorismate = isochorismate
K90 is the base that activates water for nucleophilic attack at the chorismate C2 carbon
chorismate = isochorismate
isochorismate synthase (IS) performs a 1,5-displacement mechanism during the chorismate conversion to intermediates through the use of a nucleophile, which is water in the case of IS, but might also be possible with ammonia. The hydroxyl group in the isochorismate is generated from water and not through an intramolecular rearrangement
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isochorismate hydroxymutase
Requires Mg2+. The reaction is reversible.
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isochorismate
chorismate
-
-
-
r
Chorismate
Isochorismate
-
-
-
?
Chorismate
Isochorismate
-
-
-
ir
Chorismate
?
-
the first enzyme involved in the biosynthesis of the powerful iron-chelating agent enterobactin
-
-
?
Chorismate
?
-
first committed step in the biosynthesis of menaquinone
-
-
?
Chorismate
?
-
enzyme catalyzes the pivotal step in enterobactin and menaquinone biosynthesis
-
-
?
Chorismate
Isochorismate
-
-
-
?
Chorismate
Isochorismate
-
-
-
?
Chorismate
Isochorismate
-
-
-
?
Chorismate
Isochorismate
-
-
-
-
?
Chorismate
Isochorismate
-
-
-
?
Chorismate
Isochorismate
-
not reversible, isochorismate synthase involved in enterobactin biosynthesis, MenF
-
?
Chorismate
Isochorismate
-
r, isochorismate synthase involved in menaquinone biosynthesis, EntC
-
?
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isochorismate
chorismate
-
-
-
r
Chorismate
Isochorismate
-
-
-
-
?
Chorismate
?
-
the first enzyme involved in the biosynthesis of the powerful iron-chelating agent enterobactin
-
-
?
Chorismate
?
-
first committed step in the biosynthesis of menaquinone
-
-
?
Chorismate
?
-
enzyme catalyzes the pivotal step in enterobactin and menaquinone biosynthesis
-
-
?
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Mg2+
required
Mg2+
required for catalysis
Mg2+
strongly dependent on, magnesium ions interact with chorismate in the active site, forming a magnesium-coordinated transition state during the reaction
Mg2+
-
sharp increase in activity, optimal concentration: 1 mM, inhibition above 1 mM
Mg2+
the enzyme contains Mg2+
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(4R,5R)-5-(carboxymethoxy)-4-hydroxycyclohex-1-ene-1-carboxylic acid
-
(4R,5R)-5-[(1-carboxyethenyl)oxy]-4-hydroxycyclohex-1-ene-1-carboxylic acid
inhibition of isochorismate synthase activity and salicylate synthase activity
(4R,5R)-5-[(1R)-1-carboxyethoxy]-4-hydroxycyclohex-1-ene-1-carboxylic acid
-
(4R,5R)-5-[(1S)-1-carboxyethoxy]-4-hydroxycyclohex-1-ene-1-carboxylic acid
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(4R,5R)-5-[(2-carboxyprop-2-en-1-yl)oxy]-4-hydroxycyclohex-1-ene-1-carboxylic acid
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(4R,5R,6S)-6-amino-5-[(1-carboxyethenyl)oxy]-4-hydroxycyclohex-1-ene-1-carboxylic acid
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(4R,5S,6S)-4-amino-5-[(1-carboxyethenyl)oxy]-6-hydroxycyclohex-1-ene-1-carboxylic acid
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(4R,5S,6S)-5-[(1-carboxyethenyl)oxy]-4,6-dihydroxycyclohex-1-ene-1-carboxylic acid
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(4R,5R)-4-hydroxy-5-(1-carboxyvinyloxy)-cyclohex-1-ene carboxylate
-
-
(4R,5R)-4-hydroxy-5-carboxymethoxy-cyclohex-1-enecarboxylate
-
-
(4R,5R)-5-(2-carboxy-allyloxy)-4-hydroxy-cyclohex-1-enecarboxylate
-
-
(4R,5R,6S)-6-ammonio-5-[(1-carboxylatoethenyl)oxy]-4-hydroxycyclohex-1-ene-1-carboxylate
-
-
(4R,5R,7R)-5-(1-carboxy-ethoxy)-4-hydroxy-cyclohex-1-enecarboxylate
-
-
(4R,5R,7S)-5-(1-carboxy-ethoxy)-4-hydroxy-cyclohex-1-enecarboxylate
-
-
(4R,5S,6S)-4-ammonio-5-[(1-carboxylatoethenyl)oxy]-6-hydroxycyclohex-1-ene-1-carboxylate
-
-
(4R,5S,6S)-5-[(1-carboxylatoethenyl)oxy]-4,6-dihydroxycyclohex-1-ene-1-carboxylate
-
-
additional information
inhibitor structure-function relationship and molecular docking
-
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2-mercaptoethanol
-
stimulates, 2.25fold stimulation at 20-30 mM
dithiothreitol
-
stimulates, 2fold stimulation at 1 mM
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0.192
chorismate
wild-type, pH 7.5, 37°C
0.319
chorismate
mutant L255A, pH 7.5, 37°C
0.007
chorismate
wild type enzyme, in 100 mM phosphate pH 7.0, 10 mM MgCl2
0.04
chorismate
mutant enzyme F327Y/F359Q, in 100 mM phosphate pH 7.0, 10 mM MgCl2
0.066
chorismate
mutant enzyme F359Q, in 100 mM phosphate pH 7.0, 10 mM MgCl2
0.076
chorismate
mutant enzyme F327Y, in 100 mM phosphate pH 7.0, 10 mM MgCl2
0.076
chorismate
mutant enzyme I346L, in 100 mM phosphate pH 7.0, 10 mM MgCl2
0.103
chorismate
mutant enzyme A303T, in 100 mM phosphate pH 7.0, 10 mM MgCl2
0.261
chorismate
mutant enzyme F359Q/I346L, in 100 mM phosphate pH 7.0, 10 mM MgCl2
0.466
chorismate
mutant enzyme F327Y/I346L, in 100 mM phosphate pH 7.0, 10 mM MgCl2
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0.031
chorismate
mutant L255A, pH 7.5, 37°C
0.35
chorismate
wild-type, pH 7.5, 37°C
0.05
chorismate
mutant enzyme F327Y/I346L, in 100 mM phosphate pH 7.0, 10 mM MgCl2
0.067
chorismate
mutant enzyme A303T, in 100 mM phosphate pH 7.0, 10 mM MgCl2
0.13
chorismate
mutant enzyme F327Y, in 100 mM phosphate pH 7.0, 10 mM MgCl2
0.18
chorismate
mutant enzyme F359Q/I346L, in 100 mM phosphate pH 7.0, 10 mM MgCl2
0.43
chorismate
mutant enzyme F327Y/F359Q, in 100 mM phosphate pH 7.0, 10 mM MgCl2
0.55
chorismate
mutant enzyme I346L, in 100 mM phosphate pH 7.0, 10 mM MgCl2
0.6
chorismate
mutant enzyme F359Q, in 100 mM phosphate pH 7.0, 10 mM MgCl2
0.67
chorismate
wild type enzyme, in 100 mM phosphate pH 7.0, 10 mM MgCl2
1.33
chorismate
-
in absence of 2-mercaptoethanol
2.93
chorismate
-
in presence of 2-mercaptoethanol
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0.11
chorismate
mutant enzyme F327Y/I346L, in 100 mM phosphate pH 7.0, 10 mM MgCl2
0.65
chorismate
mutant enzyme A303T, in 100 mM phosphate pH 7.0, 10 mM MgCl2
0.69
chorismate
mutant enzyme F359Q/I346L, in 100 mM phosphate pH 7.0, 10 mM MgCl2
1.71
chorismate
mutant enzyme F327Y, in 100 mM phosphate pH 7.0, 10 mM MgCl2
7.24
chorismate
mutant enzyme I346L, in 100 mM phosphate pH 7.0, 10 mM MgCl2
9.1
chorismate
mutant enzyme F359Q, in 100 mM phosphate pH 7.0, 10 mM MgCl2
10.75
chorismate
mutant enzyme F327Y/F359Q, in 100 mM phosphate pH 7.0, 10 mM MgCl2
95.7
chorismate
wild type enzyme, in 100 mM phosphate pH 7.0, 10 mM MgCl2
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0.03 - 0.16
(4R,5R)-5-[(1-carboxyethenyl)oxy]-4-hydroxycyclohex-1-ene-1-carboxylic acid
0.000053
(4R,5R,6S)-6-amino-5-[(1-carboxyethenyl)oxy]-4-hydroxycyclohex-1-ene-1-carboxylic acid
pH and temperature not specified in the publication
0.00046
(4R,5S,6S)-4-amino-5-[(1-carboxyethenyl)oxy]-6-hydroxycyclohex-1-ene-1-carboxylic acid
pH and temperature not specified in the publication
0.00036
(4R,5S,6S)-5-[(1-carboxyethenyl)oxy]-4,6-dihydroxycyclohex-1-ene-1-carboxylic acid
pH and temperature not specified in the publication
0.03
(4R,5R)-4-hydroxy-5-(1-carboxyvinyloxy)-cyclohex-1-ene carboxylate
-
-
2
(4R,5R)-4-hydroxy-5-carboxymethoxy-cyclohex-1-enecarboxylate
-
IC50 above 2.0 mM
2
(4R,5R)-5-(2-carboxy-allyloxy)-4-hydroxy-cyclohex-1-enecarboxylate
-
IC50 above 2.0 mM
0.00005
(4R,5R,6S)-6-ammonio-5-[(1-carboxylatoethenyl)oxy]-4-hydroxycyclohex-1-ene-1-carboxylate
-
-
2
(4R,5R,7R)-5-(1-carboxy-ethoxy)-4-hydroxy-cyclohex-1-enecarboxylate
-
IC50 above 2.0 mM
2
(4R,5R,7S)-5-(1-carboxy-ethoxy)-4-hydroxy-cyclohex-1-enecarboxylate
-
IC50 above 2.0 mM
0.00045
(4R,5S,6S)-4-ammonio-5-[(1-carboxylatoethenyl)oxy]-6-hydroxycyclohex-1-ene-1-carboxylate
-
-
0.00036
(4R,5S,6S)-5-[(1-carboxylatoethenyl)oxy]-4,6-dihydroxycyclohex-1-ene-1-carboxylate
-
-
0.03
(4R,5R)-5-[(1-carboxyethenyl)oxy]-4-hydroxycyclohex-1-ene-1-carboxylic acid
pH and temperature not specified in the publication, inhibition of isochorismate synthase activity
0.16
(4R,5R)-5-[(1-carboxyethenyl)oxy]-4-hydroxycyclohex-1-ene-1-carboxylic acid
pH and temperature not specified in the publication, inhibition of salicylate synthase activity
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6.5 - 9
-
about 20% of maximal activity at pH 6.5 and pH 9.0
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15 - 50
-
15°C: 72% of maximal activity, 20°C: about 74% of maximal activity, 30°C or 40°C: about 80% of maximal activity, 50°C: 42% of maximal activity
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SwissProt
brenda
menaquinone-specific enzyme
SwissProt
brenda
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metabolism
the first committed step during the biosynthesis of siderophores, which are small molecules capable of chelating iron from the host organism, is the conversion of chorismate into isochorismate by isochorismate synthase (EC 5.4.4.2) and consequently to salicylate by isochorismate pyruvate-lyase (EC 4.2.99.21). Salicylate synthase converts chorismate into salicylate through a two-step reaction
physiological function
chorismate-utilizing enzymes (CUE) such as chorismate mutase, anthranilate synthase, chorismate pyruvate-lyase, 4-amino-4-deoxychorismate synthase, isochorismate synthase and salicylate synthase are responsible for converting chorismate into various products necessary for the survival of bacteria
additional information
enzyme three-dimensional structure analysis, the lysine residue, Lys190, might be involved in the activation of water molecules and the subsequent nucleophilic attack on the C2 carbon of chorismate without directly involving the magnesium ion, participation of the Lys residue during the activation of the substrate or nucleophilic agent
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42000
-
isochorismate synthase involved in menaquinone biosynthesis, EntC, gel filtration
43000
-
1 * 43000, isochorismate synthase involved in menaquinone biosynthesis, EntC, SDS-PAGE
48000
-
2 * 48000, isochorismate synthase involved in enterobactin biosynthesis, MenF, SDS-PAGE
48777
-
x * 48777, isochorismate synthase involved in menaquinone biosynthesis, calculation from nucleotide sequence
49000
-
x * 49000, isochorismate synthase involved in menaquinone biosynthesis, SDS-PAGE
98000
-
isochorismate synthase involved in enterobactin biosynthesis, MenF, gel filtration
additional information
-
identification and sequencing of the gene menF that encodes the enzyme that is responsible for menaquinone biosynthesis. The sequence of MenF is 23.5% identical and 57.8% similar to that of EntC
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dimer
-
2 * 48000, isochorismate synthase involved in enterobactin biosynthesis, MenF, SDS-PAGE
?
-
x * 48777, isochorismate synthase involved in menaquinone biosynthesis, calculation from nucleotide sequence
?
-
x * 49000, isochorismate synthase involved in menaquinone biosynthesis, SDS-PAGE
monomer
-
-
monomer
-
1 * 43000, isochorismate synthase involved in menaquinone biosynthesis, EntC, SDS-PAGE
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enzyme without Mg2+, hanging drop vapour diffusion method, using 0.2 M trisodium citrate, 6% glycerol, 8% PEG 3350, enzyme in complex with Mg2+, sitting drop vapour diffusion method, using 0.1 M bis-tris pH 6.5, 20% PEG MME 5000
in complex with isochorismate and Mg2+, hanging drop vapor diffusion method, using 100 mM MES buffer pH 6.5, 12% PEG (w/v) 20000
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A344T
no catalytic activity
E240Q
no catalytic activity
K90A
no catalytic activity
L255A
50% increase in Km value, 90% decrease in kcat value
R387A
no catalytic activity
A303T
the kcat/Km (chorismate) for the A303T mutant is 130fold lower than that for wild type enzyme
A303T/F327Y
the mutant shows no detectable activity
A303T/F327Y/F359Q
the mutant shows no detectable activity
A303T/F327Y/F359Q/I346L
the mutant shows no detectable activity
A303T/F327Y/I346L
the mutant shows no detectable activity
A303T/F359Q
the mutant shows no detectable activity
F327Y
the mutant displays reduced activity compared to the wild type enzyme
F327Y/F359Q
the mutant displays a reduced kcat/Km value compared to the wild type enzyme
F327Y/F359Q/I346L
the mutant shows no detectable activity
F359Q/I346L
the mutant displays a reduced kcat/Km value compared to the wild type enzyme
I346L
the EntC mutant has a 12fold lower kcat/Km (chorismate) than the wild type enzyme
L304A
the mutation causes loss of catalytic activity
L304A/F359Q
the mutant shows no detectable activity
F359Q
the mutant displays a reduced kcat/Km value compared to the wild type enzyme
F359Q
the mutation causes loss of catalytic activity
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-20°C, 40% loss of activity after 5 days. 1% bovine serum albumin, 10% glycerol, or 20% dimethyl sulfoxide stabilize for up to 10 days
-
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Co2+-ion affinity chromatography
Ni2+-charged HiTrap chelating agarose column chromatography and Superdex 75 gel filtration
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expressed in Escherichia coli strain BL21 (DE3)
expressed in Brassica rapa subsp. oleifera
-
expressed in Escherichia coli BL21(DE3) cells
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Liu, J.; Quinn, N.; Berchthold, G.A.; Walsh, C.T.
Overexpression, purification, and characterization of isochorismate synthase (EnrC), the first enzyme involved in the biosynthesis of Enterobactin from Chorismate
Biochemistry
29
1417-1425
1990
Escherichia coli
brenda
Daruwala, R.; Bhattacharyya, D.K.; Kwon, O.; Meganathan, R.
Menaquinone (vitamin K2) biosynthesis: overexpression, purification, and characterization of a new isochorismate synthase from Escherichia coli
J. Bacteriol.
179
3133-3138
1997
Escherichia coli
brenda
Schaaf, P.M.; Heide, L.E.; Leistner, E.W.; Tani, Y.; Karas, M.; Deutzmann, R.
Properties of isochorismate hydroxymutase from Flavobacterium K3-15
J. Nat. Prod.
56
1294-1303
1993
Klebsiella aerogenes, Escherichia coli, Flavobacterium sp., Flavobacterium sp. 238-7, Flavobacterium sp. K3-15
brenda
Daruwala, R.; Kwon, O.; Meganathan, R.; Hudspeth, M.E.S.
A new isochorismate synthase specifically involved in menaquinone (vitamin K2) biosynthesis encoded by the menF gene
FEMS Microbiol. Lett.
140
159-163
1996
Escherichia coli
brenda
Muller, R.; Dahm, C.; Schulte, G.; Leistner, E.
An isochorismate hydroxymutase isogene in Escherichia coli
FEBS Lett.
378
131-134
1996
Escherichia coli
brenda
Kolappan, S.; Zwahlen, J.; Zhou, R.; Truglio, J.J.; Tonge, P.J.; Kisker, C.
Lysine 190 is the catalytic base in MenF, the menaquinone-specific isochorismate synthase from Escherichia coli: implications for an enzyme family
Biochemistry
46
946-953
2007
Escherichia coli (P38051), Escherichia coli
brenda
Parsons, J.F.; Shi, K.M.; Ladner, J.E.
Structure of isochorismate synthase in complex with magnesium
Acta Crystallogr. Sect. D
64
607-610
2008
Escherichia coli (P38051)
brenda
Sridharan, S.; Howard, N.; Kerbarh, O.; B?aszczyk, M.; Abell, C.; Blundell, T.L.
Crystal structure of Escherichia coli enterobactin-specific isochorismate synthase (EntC) bound to its reaction product isochorismate: implications for the enzyme mechanism and differential activity of chorismate-utilizing enzymes
J. Mol. Biol.
397
290-300
2010
Escherichia coli (P0AEJ2), Escherichia coli
brenda
Payne, R.J.; Bulloch, E.M.; Toscano, M.M.; Jones, M.A.; Kerbarh, O.; Abell, C.
Synthesis and evaluation of 2,5-dihydrochorismate analogues as inhibitors of the chorismate-utilising enzymes
Org. Biomol. Chem.
7
2421-2429
2009
Escherichia coli
brenda
Simoh, S.; Linthorst, H.J.; Lefeber, A.W.; Erkelens, C.; Kim, H.K.; Choi, Y.H.; Verpoorte, R.
Metabolic changes of Brassica rapa transformed with a bacterial isochorismate synthase gene
J. Plant Physiol.
167
1525-1532
2010
Escherichia coli
brenda
Svarcova, M.; Kratky, M.; Vinsova, J.
Investigation of potential inhibitors of chorismate-utilizing enzymes
Curr. Med. Chem.
22
1383-1399
2015
no activity in Homo sapiens, Yersinia pestis, Yersinia enterocolitica, Escherichia coli (P38051), Mycobacterium tuberculosis (P9WFX1), Pseudomonas aeruginosa (Q51508)
brenda