Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
(1R,2S)-1,2-epoxypropylphosphonic acid
-
-
(2R)-2-(phosphonooxy)propanoic acid
-
mimicking phosphohemiketal 2 (instable), competitive to substrate phosphoenolpyruvate
(2S)-2,7-bis(phosphonooxy)heptanoic acid
-
(2S)-2-(phosphonooxy)propanoic acid
-
mimicking phosphohemiketal 2 (instable), competitive to substrate phosphoenolpyruvate
(2Z)-3-phosphono-2-(trifluoromethyl)prop-2-enoic acid
-
trifluorinated phosphonate
(E)-2-methyl-3-phosphonoacrylic acid
-
most potent of the tested inhibitors mimicking intermediates in the reaction, vinyl phosphonate 4
(Z)-Phosphoenol 3-fluoropyruvate
-
-
1,10-phenanthroline
-
activity is restored by Fe2+ or Zn2+
2,3-bisphosphoglycerate
-
-
2-(phosphonomethyl)prop-2-enoic acid
-
mimics substrate phosphoenolpyruvate, and should be inert due to alkene structure but lacking an electron-donor, acts as competitive inhibitor
2-Methyl-DL-Trp
-
0.02 mM, 30% inhibition
2-phosphoglycerate
-
competitive with respect to phosphoenolpyruvate
3,4-dihydroxycinnamate
-
isoenzyme DS-Co
3-deoxy-D-arabino-heptonic acid 7-phosphate
-
-
3-deoxy-D-arabinoheptulosonate-7-phosphate oxime
3-deoxy-D-erythro-hept-2-ulosonate 7-phosphate
-
-
3-Methylphosphoenolpyruvate
-
-
3-Propylphosphoenolpyruvate
-
-
3-pyridine carboxyaldehyde
-
4-Methyl-DL-Trp
-
0.02 mM, 30% inhibition
5,5'-dithiobis(2-nitrobenzoate)
-
-
5-Fluoro-DL-Trp
-
0.02 mM, 56% inhibition
5-hydroxy-DL-Trp
-
0.02 mM, 10% inhibition
6-Methyl-DL-Trp
-
0.02 mM, 6% inhibition
7-Aza-DL-Trp
-
0.02 mM, 9% inhibition
7-Methyl-DL-Trp
-
0.02 mM, 14% inhibition
7-phospho-2-dehydro-3-deoxy-D-arabino-heptonate
allylpyrocatechol-3,4-diacetate
-
alpha-Methylphenylalanine
-
-
beta-2-Thienyl-D,L-Ala
-
-
CN-
-
Tyr-sensitive isozyme, strong inhibition, reactivation by divalent cations only to a small extent
D-fructose 1,6-diphosphate
-
-
D-sedoheptulose 1,7-diphosphate
-
-
D-sedoheptulose 7-phosphate
-
-
diethyl dicarbonate
-
Phe-sensitive isozyme, pH-dependent, phosphoenolpyruvate protects wild-type and mutants H64G, H207G, H304G
dihydroxyphenylalanine
-
-
DL-Dibromotryptophan
-
0.02 mM, 52% inhibition
DL-erythro-beta-Methyltryptophan
-
0.02 mM, 40% inhibition
DL-Homotryptophan
-
0.02 mM, 46% inhibition
eupalitin-3-O-galactoside
-
fosmidomycin
-
uncompetitive inhibitor, maximum level of inhibition after 10 min incubation, extent of inhibition dependent on the type of the metal cofactor, competitive inhibitor with respect to phosphoenolpyruvate
H2O2
DAHP synthase enzymes are inactivated by H2O2 in vitro and in vivo, H2O2 displaces the iron atom from the enzyme, only the Fe2+-metalloform of the enzyme can be inactivated by hydrogen peroxide or superoxide
Hg2+
-
complete inhibition at 1 mM
iodoacetamide
-
alkylation, abolishes the dependence on reducing agents
L-arogenate
-
isozyme DS-Mn, competitive against D-erythrose 4-phosphate, non-competitive against phosphoenolpyruvate
m-Chlorophenylalanine
-
-
m-Fluorophenylalanine
-
-
m-hydroxyphenylalanine
-
-
Mg2+
-
no inhibition of mutant C67L; wild-type and mutants
N-alpha-methyl-DL-Trp
-
0.02 mM, 60% inhibition
N-[Phosphomonomethyl]glycine
o-chlorophenylalanine
-
-
o-Fluorophenylalanine
-
-
o-hydroxyphenylalanine
-
-
p-chloromercuribenzoate
-
complete inhibition at 0.02 mM, reversible by cysteine
p-Fluorophenylalanine
-
-
p-hydroxymercuribenzoate
-
-
phenylpyruvate
-
DAHP synthase-tyr
Phosphoenol 2-oxobutanoate
-
-
phosphoenolpyruvate
pronounced substrate inhibition above 1 mM
shikimate
-
1 mM, 3% residual activity
superoxide
displaces the iron atom from the enzyme, only the Fe2+-metalloform of the enzyme can be inactivated by hydrogen peroxide or superoxide. Superoxide stress promotes the mismetallation of DAHP synthase
tetraammonium (((carboxymethyl)[(2S,3R,4S)-2,3,4-trihydroxy-5-(phosphonatooxy)pentyl]amino)methyl)phosphonate
-
IC50: 0.0066 mM
Trinitrobenzene sulfonate
-
-
[(1E)-7-bromo-2-carboxyhept-1-en-1-yl]phosphonate
-
inhibitor based on vinyl phosphonate, designed to fit into the binding sites of both phosphoenolpyruvate and D-erythrose 4-phosphate substrates simultaneously. Competitive with respect to phosphoenolpyruvate
[2-carboxy-7-(phosphonatooxy)hept-1-en-1-yl]phosphonate
-
inhibitor based on vinyl phosphonate ratio Z:E enantiomer 1:1. Inhibitor is designed to fit into the binding sites of both phosphoenolpyruvate and D-erythrose 4-phosphate substrates simultaneously. Competitive with respect to phosphoenolpyruvate
[2-carboxy-7-(phosphonatooxy)hept-2-en-1-yl]phosphonate
-
inhibitor based on allyl phosphonate, ratio Z:E enantiomer 7:3. Inhibitor is designed to fit into the binding sites of both phosphoenolpyruvate and D-erythrose 4-phosphate substrates simultaneously. Competitive with respect to phosphoenolpyruvate
3-deoxy-D-arabinoheptulosonate-7-phosphate oxime
binding is competitive with respect to all three substrates.The oxime functional group, combined with two crystallographic waters, binds at the same location in the catalytic center as the phosphate group of the tetrahedral intermediate. DAHP oxime binds to only one subunit of each tight dimer
3-deoxy-D-arabinoheptulosonate-7-phosphate oxime
inhibitor shows a good correlation between transition state stabilization and inhibition. DAHP oxime is mimicking the first irreversible transition state of the DAHP synthase reaction, presumably phosphate departure from the tetrahedral intermediate
3-deoxy-D-arabinoheptulosonate-7-phosphate oxime
inhibition is competitive with respect to the essential metal ion, Mn2+. Inhibition shifts from metal-competitive at physiological pH to metal-noncompetitive at pH above 8.7 in response to deprotonation of the Cys61 side chain. Metal-competitive inhibition arises from interactions between Mn2+, DAHP oxime's O4 hydroxyl group, and the Cys61 and Asp326 side chains
7-phospho-2-dehydro-3-deoxy-D-arabino-heptonate
-
product inhibition
7-phospho-2-dehydro-3-deoxy-D-arabino-heptonate
-
competitive against D-erythrose 4-phosphate and phosphoenolpyruvate
chorismate
-
50% at 0.12 mM; feedback inhibition, noncompetitive against D-erythrose 4-phosphate and phosphoenolpyruvate
chorismate
-
1 mM, 3% residual activity
chorismate
-
competitive against phosphoenolpyruvate, noncompetitive against D-erythrose 4-phosphate; DAHP synthase-trp
chorismate
-
main allosteric feedback inhibitor and regulator for enzyme of class AroAII
Co2+
-
weak
Co2+
-
concentrations above 0.1 mM
Cu2+
-
weak
Cu2+
-
0.02 mM, complete inactivation; Phe-sensitive isozyme, complete inactivation at 0.02 mM, destabilization of the enzymes quarternary structure; phosphoenolpyruvate protects
D-erythrose 4-phosphate
-
-
D-erythrose 4-phosphate
Phe-sensitive isozyme: in absence of phosphoenolpyruvate the enzyme is inhibited via formation of a covalent binding to Lys186 via a slow Schiff base reaction, mechanism
D-erythrose 4-phosphate
-
substrate-inhibition
D-erythrose 4-phosphate
-
isoenzyme DS-Mn: substrate inhibition above 0.5 mM
dipicolinic acid
1 mM, 1 h, 21% residual activity
dipicolinic acid
-
inactivation, reactivation by divalent cations
EDTA
2 mM, complete inactivation within 10 min
EDTA
10 mM, 1 h, 21% residual activity
EDTA
-
22.7% residual activity at 2 mM EDTA for isozyme NCgl0950 DAHP synthase, 49.1% residual activity at 2 mM EDTA for isozyme NCgl2098 DAHP synthase
EDTA
-
reversible by Co2+
EDTA
-
activity is restored by Fe2+ or Zn2+
EDTA
-
reversible by diverse divalent metal ions with varying efficiency
EDTA
-
Mn2+, Cd2+, Co2+, Fe2+, Cu2+, Mg2+ or Zn2+ reactivate, Fe2+ and Cu2+ only partially reactivate
EDTA
-
inactivation, reactivation by divalent metyl ions, in decreasing order: Co2+, Mn2+, Ca2+, Mg2+, Cu2+, Zn2+
EDTA
-
reversible by Co2+
EDTA
-
phosphoenolpyruvate or 3-deoxy-D-arabino-heptulosonate 7-phosphate and Mn2+, Co2+, Ca2+ and Mg2+ protect
EDTA
-
inactivation, restoration in decreasing order of effectiveness by Zn2+, Cd2+, Mn2+, Co2+, Ni2+, Ca2+, Hg2+, Cu2+
EDTA
-
Co2+, Zn2+, Cu2+, and Fe3+ restore activity
EDTA
-
Co2+, Mn2+, Zn2+ and Fe2+ restore activity; phosphoenolpyruvate, 2 mM, partially protects from inactivation, does not restore activity
EDTA
-
inactivation, reactivation in decreasing order by Zn2+, Cd2+, Mn2+, Cu2+, Co2+, Ni2+
EDTA
-
strong, reversible by dialysis
Fe2+
-
0.02 mM: 60% inactivation. 0.2 mM: 90% inactivation; Phe-sensitive isozyme, 60% inactivation at 0.02 mM, 90% inactivation at 0.2 mM; phosphoenolpyruvate protects
L-Phe
-
NCgl0950 DAHP synthase is sensitive to feedback inhibition with 29.1 to 38.8% inhibition at 2 mM, NCgl2098 DAHP synthase is insensitive
L-Phe
strong feedback inhibition
L-phenylalanine
-
1 mM, 3% residual activity
L-phenylalanine
allosteric feedback inhibition
L-phenylalanine
allosteric feedback inhibition
L-phenylalanine
-
1 mM, 32% residual activity
L-phenylalanine
involved in allosteric regulation of the enzyme, inhibits the wild-type enzyme, and enzyme mutants H29A and H29S/S31H
L-Trp
-
NCgl0950 DAHP synthase is sensitive to feedback inhibition, NCgl2098 DAHP synthase is slightly sensitive to feedback inhibition with 10-15% decrease of activity at 5 mM L-Trp
L-Trp
feedback inhibition
L-tryptophan
-
1 mM, 3% residual activity
L-tryptophan
allosteric feedback inhibition
L-tryptophan
allosteric feedback inhibition
L-Tyr
-
NCgl0950 DAHP synthase is sensitive to feedback inhibition with 80% loss of activity at 0.03 mM, NCgl2098 DAHP synthase is insensitive, Tyr-linked inhibition is competitive to phophoenolpyruvate
L-Tyr
feedback inhibition
L-tyrosine
-
1 mM, 3% residual activity
L-tyrosine
feedback inhibition of isozyme AroF
L-tyrosine
feedback inhibition
L-tyrosine
allosteric feedback inhibition
L-tyrosine
allosteric feedback inhibition
L-tyrosine
-
almost complete inhibition at 0.5 mM
L-tyrosine
-
1 mM, 23% residual activity
L-tyrosine
allosteric regulation of the enzyme is mediated by L-Tyr binding to a discrete ACT regulatory domain appended to a core catalytic (beta/alpha)8 barrel, highly reduced inhibition of enzyme mutant S31G. Comparison of the position of the regulatory ACT domain of TmaDAH7PS in the unbound and L-Tyr-bound conformations, overview
N-[Phosphomonomethyl]glycine
-
i.e. glyphosate; inhibition of isozyme DS-Co in vitro and in vivo, isozyme DS-Mn is only slightly inhibited in vitro
N-[Phosphomonomethyl]glycine
-
concentration of Co2+ markedly increases the concentration of N-[phosphomonomethyl]glycine required for inhibition; cytosolic isozyme; i.e. glyphosate
Phe
-
DSI; Phe-sensitive isozyme
Phe
-
slight inhibition of the wild-type, activation of mutants
Phe
-
0.5 mM, 60% inhibition; Phe-sensitive isozyme
Phe
-
0.04 mM, 50% inhibition of DAHP synthase-phe; L-Phe; Phe-sensitive isozyme
Phe
-
L-Phe; Phe-sensitive isozyme
Phe
-
L-Phe; Phe-sensitive isozyme; strong
Phe
-
Phe-sensitive isozyme
Phe
-
feed-back inhibition, Phe-sensitive isozyme; Phe-sensitive isozyme
Phe
-
Phe-sensitive isozyme
Phe
Phe-sensitive isozyme
Phe
-
Phe-sensitive isozyme
Phe
-
competitive with respect to D-erythrose 4-phosphate and non-competitive to phosphoenolpyruvate; Tyr-sensitive isozyme is less inhibited than the Phe-sensitive isozyme
Phe
-
competitive with respect to D-erythrose 4-phosphate and non-competitive to phosphoenolpyruvate; Phe-sensitive isozyme
Phe
-
no inhibition; Phe-sensitive isozyme; strain 12/60/X, no inhibition; strain H1, strain H20 and strain 3/2: cumulative inhibition of Tyr and Phe
phenylalanine
-
1 Mn, wild-type 8.2% residual activity
phenylalanine
inhibition of the synthase-chorismate mutase complex, based on mutase activity measurements at 30°C, 50 mM BTP (1,3-bis[tris(hydroxymethyl)methylamino]propane), pH 7.5, 0.5 mM TCEP [tris(2-carboxyethyl)phosphine hydrochloride], 0.2 mM phosphoenolpyruvate, and 0.1 mM MnCl2
phosphate
-
non-competitive with respect to both phosphoenolpyruvate and D-erythrose 4-phosphate
phosphate
-
non-competitive with respect to both phosphoenolpyruvate and D-erythrose 4-phosphate
phosphate
-
non-competitive with respect to both phosphoenolpyruvate and D-erythrose 4-phosphate
phosphate
-
competitive to D-erythrose 4-phosphate, noncompetitive to phosphoenolpyruvate
phosphate
-
phosphate buffer destabilizes
prephenate
-
50% at 0.02 mM; feedback inhibition, noncompetitive against D-erythrose 4-phosphate and phosphoenolpyruvate
prephenate
-
1 mM, 3% residual activity
prephenate
-
IC50: 0.1 mM
prephenate
-
isozyme DS-Mn, competitive against D-erythrose 4-phosphate, non-competitive against phosphoenolpyruvate
Trp
-
noncompetitive to both substrates; Trp-sensitive isozyme
Trp
-
DSI; Trp-sensitive isozyme
Trp
-
Trp-sensitive isozyme
Trp
-
0.02 mM, 65% inhibition; non-competitive against phosphoenolpyruvate and competitive for D-erythrose 4-phosphate; strongly dependent on pH; Trp-sensitive isozyme
Trp
-
non-competitive against phosphoenolpyruvate and competitive for D-erythrose 4-phosphate; Trp-sensitive isozyme
Trp
-
Trp-sensitive isozyme
Trp
-
allosteric, best at pH 6.0, no inhibition at pH 7.3; Trp-sensitive isozyme
Trp
-
Trp-sensitive isozyme
Trp
-
DAHP synthase-trp; non-competitive against phosphoenolpyruvate and competitive for D-erythrose 4-phosphate; Trp-sensitive isozyme
Trp
-
Trp-sensitive isozyme
Trp
-
Trp-sensitive isozyme
Trp
-
minor feedback inhibitor
Tyr
-
DSI and DSII; Tyr-sensitive isozyme
Tyr
-
feedback inhibition; noncompetitive with respect to D-erythrose 4-phosphate, competitive with respect to phosphoenolpyruvate; Tyr-sensitive isozyme; wild-type and mutant S187A
Tyr
-
0.5 mM, 20% inhibition; Tyr-sensitive isozyme
Tyr
-
0.04 mM, 50% inhibition of DAHP synthase-tyr; L-Tyr; Tyr-sensitive isozyme
Tyr
-
0.02 mM, 50% inhibition; Tyr-sensitive isozyme
Tyr
-
feedback inhibition; noncompetitive with respect to D-erythrose 4-phosphate, competitive with respect to phosphoenolpyruvate; Tyr-sensitive isozyme
Tyr
-
L-Tyr; Tyr-sensitive isozyme
Tyr
-
Tyr-sensitive isozyme
Tyr
-
wild-type isozyme, mutant N8K and N-terminal deletion mutant are not inhibited, N-terminus is structurally involved in the sensitivity for feedback inhibition
Tyr
-
Tyr-sensitive isozyme
Tyr
-
L-Tyr; Tyr-sensitive isozyme
Tyr
-
DAHP synthase-tyr; L-Tyr; Tyr-sensitive isozyme
Tyr
-
noncompetitive with respect to D-erythrose 4-phosphate, competitive with respect to phosphoenolpyruvate; Tyr-sensitive isozyme
Tyr
-
noncompetitive with respect to D-erythrose 4-phosphate, competitive with respect to phosphoenolpyruvate; Tyr-sensitive isozyme
Tyr
-
at pH 6.2-7.8; Tyr-sensitive isozyme
Tyr
-
strain 33/X strongly but not totally inhibited; strain H1, strain H20 and strain 3/2: cumulative inhibition of Tyr and Phe; Tyr-sensitive isozyme
tyrosine
inhibition of the synthase-chorismate mutase complex, based on mutase activity measurements at 30°C, 50 mM BTP (1,3-bis[tris(hydroxymethyl)methylamino]propane), pH 7.5, 0.5 mM TCEP [tris(2-carboxyethyl)phosphine hydrochloride], 0.2 mM phosphoenolpyruvate, and 0.1 mM MnCl2
Zn2+
-
no inhibition of mutant C67L; wild-type and mutants
additional information
substrate D-erythrose 4-phosphate is not inhibitory
-
additional information
none of the downstream products of the shikimate biosynthetic pathway tested inhibits the activity of the enzyme
-
additional information
-
none of the downstream products of the shikimate biosynthetic pathway tested inhibits the activity of the enzyme
-
additional information
-
no inhibition by aromatic amino acids, folic acid, phenazine 1-carboxylic acid, anthranilic acid, shikimic acid, p-aminobenzoic acid and 3-hydroxyanthranilic acid
-
additional information
-
no inhibitory: EDTA
-
additional information
-
inhibition mechanism
-
additional information
-
structure and reaction intermediate mimic inhibitors; sulfoenolpyruvate 7 mimics substrate phosphoenolpyruvate, sulfate exchanges phosphate ester, no inhibition up to a concentration of 10 mM
-
additional information
isozyme AroG is not inhibited by L-Phe. In peroxide-stressed cells, the enzyme accumulates as an apoprotein, potentially with an oxidized cysteine residue. In superoxide-stressed cells, the enzyme acquires a nonactivating zinc ion in its active site, an apparent consequence of the repeated ejection of iron. Manganese supplementation protects the activity in both cases, which matches the ability of manganese to metallate the enzyme and to provide substantial oxidant-resistant activity. The damage to DAHP synthase can be completely restored in vivo, while in vitro, restoration is only partly, overview. Escherichia coli attempts to compensate for diminished DAHP synthase activity by increasing expression
-
additional information
-
isozyme AroG is not inhibited by L-Phe. In peroxide-stressed cells, the enzyme accumulates as an apoprotein, potentially with an oxidized cysteine residue. In superoxide-stressed cells, the enzyme acquires a nonactivating zinc ion in its active site, an apparent consequence of the repeated ejection of iron. Manganese supplementation protects the activity in both cases, which matches the ability of manganese to metallate the enzyme and to provide substantial oxidant-resistant activity. The damage to DAHP synthase can be completely restored in vivo, while in vitro, restoration is only partly, overview. Escherichia coli attempts to compensate for diminished DAHP synthase activity by increasing expression
-
additional information
no feedback inhibition by L-phenylalanine
-
additional information
-
not inhibitory: phenylalanine, tyrosine, tryptophan, chorismate
-
additional information
inhibitor screening, docking study, molecular dynamics and molecular modelling, induced fit docking scores, overview. alpha-Tocopherol, 3-pyridine carboxyaldehyde, and rutin can be drug leads to inhibit mtDAH7Ps in Mycobacterium tuberculosis
-
additional information
-
inhibitor screening, docking study, molecular dynamics and molecular modelling, induced fit docking scores, overview. alpha-Tocopherol, 3-pyridine carboxyaldehyde, and rutin can be drug leads to inhibit mtDAH7Ps in Mycobacterium tuberculosis
-
additional information
binding structure determination and analysis, overview. The side chains of enzyme residues Lys188, Arg167 and Arg236 and the main chain peptide N of Ala166 that interact with the phosphate moiety of phosphoenolpyruvate form similar interactions with the phosphate or phosphonate functionalities of the three ligands, consistent with this portion of each inhibitor being able to mimic the phosphoenolpyruvate binding characteristics well. The tetrameric quaternary structures of enzyme NmeDAH7PS bound with (S)-phospholactate and vinyl phosphonate are identical to that of the isomorphous phosphoenolpyruvate-bound parent structure, PDB ID 4HSN. The increased inhibitor potency observed for the vinyl phosphonate over the (R)-phospholactate suggests that the active site is better prepared to accommodate a planar rather than tetrahedral intermediate
-
additional information
-
binding structure determination and analysis, overview. The side chains of enzyme residues Lys188, Arg167 and Arg236 and the main chain peptide N of Ala166 that interact with the phosphate moiety of phosphoenolpyruvate form similar interactions with the phosphate or phosphonate functionalities of the three ligands, consistent with this portion of each inhibitor being able to mimic the phosphoenolpyruvate binding characteristics well. The tetrameric quaternary structures of enzyme NmeDAH7PS bound with (S)-phospholactate and vinyl phosphonate are identical to that of the isomorphous phosphoenolpyruvate-bound parent structure, PDB ID 4HSN. The increased inhibitor potency observed for the vinyl phosphonate over the (R)-phospholactate suggests that the active site is better prepared to accommodate a planar rather than tetrahedral intermediate
-
additional information
undergoes no significant conformational change on inhibitor binding, crystal structure analysis, overview. Allosteric response arising from changes in protein motion rather than conformation, and suggest ligands that modulate protein dynamics may be effective inhibitors of this enzyme
-
additional information
-
undergoes no significant conformational change on inhibitor binding, crystal structure analysis, overview. Allosteric response arising from changes in protein motion rather than conformation, and suggest ligands that modulate protein dynamics may be effective inhibitors of this enzyme
-
additional information
not inhibitory: phenylalanine, tyrosine, tryptophane
-
additional information
-
not inhibitory: phenylalanine, tyrosine, tryptophane
-
additional information
-
resistant to denaturation by sodium dodecyl sulfate, not inhibitory: phenylalanine, tyrosine, tryptophan
-
additional information
-
not inhibited by tryptophan
-
additional information
-
not inhibitory: L-tryptophan, chorismate, shikimate, D-phenylalanine, L-histidine
-
additional information
small angle X-ray (SAXS) scattering analysis
-
additional information
-
small angle X-ray (SAXS) scattering analysis
-
additional information
-
no inhibition by Tyr and Phe
-