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Information on EC 2.2.1.6 - acetolactate synthase and Organism(s) Escherichia coli and UniProt Accession P08142
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2.2.1.6 acetolactate synthaseIUBMB Comments
This enzyme requires thiamine diphosphate. The reaction shown is in the pathway of biosynthesis of valine; the enzyme can also transfer the acetaldehyde from pyruvate to 2-oxobutanoate, forming 2-ethyl-2-hydroxy-3-oxobutanoate, also known as 2-aceto-2-hydroxybutanoate, a reaction in the biosynthesis of isoleucine.
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Word Map
- 2.2.1.6
-
herbicide
-
weed
- sulfonylurea
-
als-inhibiting
-
branched-chain
- imidazolinone
-
biotype
-
cross-resistance
-
herbicide-resistant
- imazethapyr
- chlorsulfuron
- triazolopyrimidine
-
4.1.3.18
-
als-inhibitors
- glyphosate
-
target-site
- amaranthus
- imazamox
- acetoin
- sulfometuron
- 2,3-butanediol
- echinochloa
- protoporphyrinogen
-
broadleaf
- 2-ketobutyrate
-
non-target-site
-
whole-plant
- nicosulfuron
- accase
- hybridus
- rigidum
-
waterhemp
- mesotrione
-
postemergence
- crus-galli
-
safener
- 5-enolpyruvylshikimate-3-phosphate
-
ilvced
- alpha-ketobutyrate
- brewing
- rudis
- dicamba
- synthesis
- agriculture
- molecular biology
- glufosinate
-
thdp-dependent
- palmeri
- tuberculatus
- analysis
-
alopecurus
-
isomeroreductase
- pharmacology
-
herbicide-binding
- drug development
-
glyphosate-resistant
- kochia
- biotechnology
The taxonomic range for the selected organisms is: Escherichia coli
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Synonyms
acetolactate synthase, acetohydroxy acid synthase, alpha-acetolactate synthase, ahas1, ahass, ahas2, ahas ii, acetohydroxy acid synthetase, acetohydroxy acid synthase i, ahas3, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
acetohydroxy acid synthase
acetohydroxy acid synthetase
-
-
-
-
acetohydroxyacid synthase
acetolactate pyruvate-lyase (carboxylating)
-
-
-
-
acetolactate synthetase
-
-
-
-
acetolactic synthetase
-
-
-
-
AHAS
alpha-acetohydroxy acid synthetase
-
-
-
-
alpha-acetohydroxyacid synthase
-
-
-
-
alpha-acetolactate synthase
-
-
-
-
alpha-acetolactate synthetase
-
-
-
-
alpha-ALS
-
-
-
-
GST-mALS
-
-
-
-
GST-wALS
-
-
-
-
synthase, acetolactate
-
-
-
-
additional information
-
the enzyme belongs to the ThDP-dependent family of enzymes
acetohydroxy acid synthase
-
-
-
-
acetohydroxyacid synthase
-
-
-
-
AHAS
-
-
-
-
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
2 pyruvate = 2-acetolactate + CO2
specificity of carboligation and product liberation may be cumulative if the former is not completely committed
-
2 pyruvate = 2-acetolactate + CO2
catalytic mechanism via thiamine diphosphate-bound intermediates, structure-activity relationship of isozyme AHAS II
-
2 pyruvate = 2-acetolactate + CO2
catalytic mechanism, covalent intermediates
-
2 pyruvate = 2-acetolactate + CO2
the enzyme catalyzes the decarboxylation of bound pyruvate to form a hydroxyethyl-thiamine diphosphate anion/enamine intermediate, which normally reacts with a second molecule of an alpha-ketoacid to form an acetohydroxyacid, but can also perform several side reactions proceeding through the hydroxyethyl-thiamine diphosphate anion/enamine intermediate
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
C-C bond formation
-
-
-
-
decarboxylation
-
-
-
-
PATHWAY SOURCE
PATHWAYS
KEGG
-
-, -, -, -, -, -, -, -, -
SYSTEMATIC NAME
IUBMB Comments
pyruvate:pyruvate acetaldehydetransferase (decarboxylating)
This enzyme requires thiamine diphosphate. The reaction shown is in the pathway of biosynthesis of valine; the enzyme can also transfer the acetaldehyde from pyruvate to 2-oxobutanoate, forming 2-ethyl-2-hydroxy-3-oxobutanoate, also known as 2-aceto-2-hydroxybutanoate, a reaction in the biosynthesis of isoleucine.
CAS REGISTRY NUMBER
COMMENTARY
9027-45-6
-
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
2-oxobutanoate + pyruvate
2-propionyl-2-hydroxybutanoate + ?
-
reaction catalyzed by mutant V375A
-
-
?
2-oxobutyrate
2-ethyl-2-hydroxy-3-oxopentanoate + CO2
-
-
-
ir
pyruvate + 2-oxobutyrate
(S)-acetohydroxybutyrate + CO2
-
stereospecific reaction
-
-
?
pyruvate + O2
peracetate + CO2
-
isozymes AHAS II and AHAS III, oxygen-consuming side reaction
-
-
?
2 pyruvate
2-acetolactate + CO2
-
60fold higher specificity for 2-ketobutyrate over pyruvate as acceptor
-
-
?
2 pyruvate
2-acetolactate + CO2
irreversible decarboxylation of pyruvate
-
-
ir
2-oxobutanoate + pyruvate
2-hydroxy-2-methyl-3-oxopentanoate + CO2
-
-
-
-
?
2-oxobutanoate + pyruvate
2-hydroxy-2-methyl-3-oxopentanoate + CO2
-
60fold higher specificity for 2-ketobutyrate over pyruvate as acceptor
-
-
?
pyruvate
(S)-2-acetolactate + CO2
-
the enzyme is the first common enzyme in the pathway for the biosynthesis of branched-chain amino acids, overview
-
-
?
pyruvate
2-acetolactate + CO2
-
first step in the biosynthesis of valine, overview
-
-
r
pyruvate
2-acetolactate + CO2
-
the enzyme catalyzes the first committed step in the biosynthesis of valine, leucine, and isoleucine
-
-
?
pyruvate
?
-
production of isoenzyme AHS I is under multivalent control by Val and Leu, production of isoenzyme AHS II is under multivalent control by Ile, Val and Leu
-
-
?
pyruvate
?
-
isoenzyme AHAS I enables a bacterium to cope with poor carbon sources, which lead to low endogenous pyruvate concentrations
-
-
?
pyruvate
?
-
first enzyme unique to biosynthesis of the branched chain amino acids Val, Leu, and Ile
-
-
?
pyruvate + 2-oxobutanoate
acetohydroxybutanoate
-
isoenzyme I shows no product preference, isoenzymes II and III form acetohydroxybutanoate at 180fold and 60fold faster rates, respectively than acetolactate
-
?
pyruvate + 2-oxobutyrate
2-aceto-2-hydroxybutyrate + CO2
irreversible decarboxylation of pyruvate
-
-
ir
pyruvate + benzaldehyde
(R)-phenylacetylcarbinol + CO2
-
stereospecific reaction
-
-
?
pyruvate + benzaldehyde
(R)-phenylacetylcarbinol + CO2
-
stereospecific reaction, benzaldehyde is an artificial substrate, especially of mutants of isozyme AHAS II residues Phe109, Met250, Arg276 and Trp464
-
-
?
pyruvate + benzaldehyde
(R)-phenylacetylcarbinol + CO2
-
stereospecific reaction, isozymes AHAS I and II
-
-
?
additional information
?
-
-
mechanism of expression regulation, overview
-
-
?
additional information
?
-
-
acetohydroxybutyrate is preferably formed, isozyme AHAS I can also form peracetate from synthetic acetolactate
-
-
?
additional information
?
-
-
substrate specificity ratios of isozymes I-III, substrate recognition mechanism, overview
-
-
?
additional information
?
-
-
AHAS catalyses the first step leading to all three branched-chain amino acids, in the reactions, enzyme-bound thiamine diphosphate reacts with pyruvate, releasing CO2 and forming an acetaldehyde moiety as enzyme-bound hydroxyethyl-ThDP, resonating enamine/alpha-carbanion intermediate
-
-
?
additional information
?
-
-
the specificity of AHAS for 2-ketoacids as acceptor substrates is due to an arginine residue which probably interacts with the carboxylate of the second substrate, e.g., Arg276 in AHAS II. Mutants altered at this arginine can utilize aromatic aldehydes as second substrate and form chiral arylacyl carbinols. Mechanistically, carboligation occurs after rate-determining formation of hydroxyethyl-thiamine diphosphate. A faster rate constant for product release when the alkyl group derived from the acceptor substrate is ethyl compared to methyl plays a major role in product specificity. The crucial role of a Trp residue, i.e. Trp 464 in AHAS II, in determining specificity may be due to control of a conformational change involved in product release rather than to affinity for 2-ketobutyrate
-
-
?
additional information
?
-
-
a valine and a phenylalanine residue hydrophobically interact with the methyl substituent of pyruvate. A mutation of either Val375 or Phe109 is detrimental for unimolecular catalytic steps in which tetrahedral intermediates are involved, such as substrate addition to the cofactor and product liberation. Val375 and Phe109 to not only conjointly mediate substrate binding and specificity but moreover to ensure a proper orientation of the donor substrate and intermediates for correct orbital alignment in multiple transition states
-
-
?
additional information
?
-
-
isozyme I is not specific for 2-oxobutanoate over pyruvate as an acceptor substrate. Residues Gln480 and Met476 in AHAS I replace the Trp and Leu residues conserved in other acetohydroxyacid synthases and lead to accelerated ligation and product release steps. This difference in kinetics accounts for the unique specificity, reversibility and allosteric response of AHAS I
-
-
?
additional information
?
-
-
residue Glu47 has a crucial catalytic role for it in the carboligation of the acceptor and the hydroxyethyl-thiamine diphosphate enamine intermediate. The Glu47-cofactor proton shuttle acts in concert with Gln110 in the carboligation. Either the transient oxyanion on the acceptor carbonyl is stabilized by H-bonding to the glutamine side chain, or carboligation involves glutamine tautomerization and the elementary reactions of addition and protonation occur in a concerted manner. Gln110 and Glu47 have global catalytic roles, being engaged in all major bond-breaking and bond-making steps. Lys159 has a minor effect on the kinetics and specificity of isoform AHAS II, far less than does Arg276,which influences the specificity for a 2-ketoacid as a second substrate. His251 has a large effect on donor substrate binding, but this effect masks any other effects of replacement of His251
-
-
?
additional information
?
-
P00892; P0ADG1
the product of this enzyme-catalyzed reaction is either 2-acetolactate or 2-aceto-2-hydroxybutyrate obtained from self-condensation of pyruvate or condensation of pyruvate and 2-oxobutyrate, respectively. Substrate specificities of isozymes: isozymes AHAS II and AHAS III prefer 2-oxobutyrate as the second substrate whereas such selectivity is not observed in case of isozyme AHAS I. Isozymes AHAS I and AHAS II are capable of self condensing 2-oxobutyrate to form 2-ethyl-2-hydroxy-3-oxopentanoate
-
-
?
additional information
?
-
the product of this enzyme-catalyzed reaction is either 2-acetolactate or 2-aceto-2-hydroxybutyrate obtained from self-condensation of pyruvate or condensation of pyruvate and 2-oxobutyrate, respectively. Substrate specificities of isozymes: isozymes AHAS II and AHAS III prefer 2-oxobutyrate as the second substrate whereas such selectivity is not observed in case of isozyme AHAS I. Isozymes AHAS I and AHAS II are capable of self condensing 2-oxobutyrate to form 2-ethyl-2-hydroxy-3-oxopentanoate
-
-
?
additional information
?
-
the product of this enzyme-catalyzed reaction is either 2-acetolactate or 2-aceto-2-hydroxybutyrate obtained from self-condensation of pyruvate or condensation of pyruvate and 2-oxobutyrate, respectively. Substrate specificities of isozymes: isozymes AHAS II and AHAS III prefer 2-oxobutyrate as the second substrate whereas such selectivity is not observed in case of isozyme AHAS I. Isozymes AHAS I and AHAS II are capable of self condensing 2-oxobutyrate to form 2-ethyl-2-hydroxy-3-oxopentanoate
-
-
?
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
2-oxobutyrate
2-ethyl-2-hydroxy-3-oxopentanoate + CO2
-
-
-
ir
pyruvate
(S)-2-acetolactate + CO2
-
the enzyme is the first common enzyme in the pathway for the biosynthesis of branched-chain amino acids, overview
-
-
?
pyruvate + 2-oxobutyrate
(S)-acetohydroxybutyrate + CO2
-
stereospecific reaction
-
-
?
2 pyruvate
2-acetolactate + CO2
irreversible decarboxylation of pyruvate
-
-
ir
pyruvate
2-acetolactate + CO2
-
first step in the biosynthesis of valine, overview
-
-
r
pyruvate
2-acetolactate + CO2
-
the enzyme catalyzes the first committed step in the biosynthesis of valine, leucine, and isoleucine
-
-
?
pyruvate
?
-
production of isoenzyme AHS I is under multivalent control by Val and Leu, production of isoenzyme AHS II is under multivalent control by Ile, Val and Leu
-
-
?
pyruvate
?
-
isoenzyme AHAS I enables a bacterium to cope with poor carbon sources, which lead to low endogenous pyruvate concentrations
-
-
?
pyruvate
?
-
first enzyme unique to biosynthesis of the branched chain amino acids Val, Leu, and Ile
-
-
?
pyruvate + 2-oxobutyrate
2-aceto-2-hydroxybutyrate + CO2
irreversible decarboxylation of pyruvate
-
-
ir
additional information
?
-
-
mechanism of expression regulation, overview
-
-
?
additional information
?
-
-
AHAS catalyses the first step leading to all three branched-chain amino acids, in the reactions, enzyme-bound thiamine diphosphate reacts with pyruvate, releasing CO2 and forming an acetaldehyde moiety as enzyme-bound hydroxyethyl-ThDP, resonating enamine/alpha-carbanion intermediate
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
FAD
-
absolutly required for isoenzyme I and II, no requirement for isoenzyme III
FAD
-
the flavin plays a crucial role in the structural integrity, and is reduced in the course of catalysis as a result of an internal redox side reaction
FAD
-
required, presence of FAD in AHAS is an evolutionary relic of the ancestry of its sub-family of ThDP-dependent enzymes
FAD
-
the secondary structure of the FAD binding domain of large subunit ilvB is similar to the structure of this domain in the catalytic subunit of yeast AHAS. The regulatory subunit ilvN interacts with ilvBalpha and ilvBbeta domains of the catalytic subunit and not with the ilvBgamma domain. ilvN binds close to the FAD binding site in ilvBbeta and proximal to the intrasubunit ilvBalpha/ilvBbeta domain interface
FAD
the anabolic enzyme form is dependent on the presence of FAD, structure of the enamine-FAD adduct, reaction mechanism molecular modeling
thiamine diphosphate
-
Km: 0.0087 mM for isoenzyme I, 0.026 mM for isoenzyme III
thiamine diphosphate
-
dependent on, the bound cofactor adopts a V-conformation in the active site, fixing the 4'-NH2 group very close to the C2-H of the thiazolium group
thiamine diphosphate
-
required, ThDP is anchored in the active site by a divalent metal ion cofactor such as Mg2+
thiamine diphosphate
-
residue Glu47 is involved in cofactor activation, substrate binding, and product elimination and plays a crucial catalytic role in the carboligation of the acceptor and the hydroxyethyl-thiamine diphosphate enamine intermediate. The Glu47-cofactor proton shuttle acts in concert with Gln110 in the carboligation
thiamine diphosphate
dependent on, upon removal of the cofactor, the activity of the enzyme is completely abolished and again restored by readdition of thiamine diphosphate. ThDP has a central role in the enzymes catalytic mechanism. In the active site of enzyme, it is located at its centre with a unique V-conformation at the dimer interface. Decarboxylation of pyruvate is carried out by ThDP
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Mg2+
additional information
Mg2+
-
wild-type, Km-value 0.01 mM, mutant D428N, Km-value 0.21 mM, mutant D428E, Km-value 0.36 mM
Mg2+
-
the enzyme requires a divalent metal ion, involved in anchoring the thiamine diphosphate cofactor in the active site
Mg2+
a bivalent metal cation is required
additional information
P00892; P0ADG1
enzyme AHAS is not specific as far as metal ions are concerned. It is active in presence of any metal ion like Mn2+, Mg2+, Ca2+, Cd2+. Modeling of the activity of the metal ions in the catalytic mechanism of isozyme AHAS II
additional information
enzyme AHAS is not specific as far as metal ions are concerned. It is active in presence of any metal ion like Mn2+, Mg2+, Ca2+, Cd2+. Modeling of the activity of the metal ions in the catalytic mechanism of isozyme AHAS II
additional information
enzyme AHAS is not specific as far as metal ions are concerned. It is active in presence of any metal ion like Mn2+, Mg2+, Ca2+, Cd2+. Modeling of the activity of the metal ions in the catalytic mechanism of isozyme AHAS II
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(5-bromo-2-[[([2-[(2-chloroethoxy)methyl]phenyl]sulfonyl)carbamoyl]amino]pyrimidin-4-yl)methyl benzoate
-
-
(5-bromo-2-[[([2-[(2-chloroethoxy)methyl]phenyl]sulfonyl)carbamoyl]amino]pyrimidin-4-yl)methyl phenylacetate
-
-
(5-bromo-2-[[([2-[(2-chloroethoxy)methyl]phenyl]sulfonyl)carbamoyl]amino]pyrimidin-4-yl)methyl prop-2-enoate
-
-
1-(4,6-dimethoxypyrimidin-2-yl)-5-methoxymethyl-N-(2-isopropyl-6-nitrophenyl)-1H-1,2,4-triazole-3-sulfonamide
-
-
1-(4,6-dimethoxypyrimidin-2-yl)-5-methyl-N-(2-isopropyl-6-nitrophenyl)-1H-1,2,4-triazole-3-sulfonamide
-
-
1-(4,6-dimethoxypyrimidin-2-yl)-5-methylthio-N-(2-chloro-6-fluorophenyl)-1H-1,2,4-triazole-3-sulfonamide
-
-
1-(4-chloro-6-methoxypyrimidin-2-yl)-5-methoxy-N-(2-methyl-6-nitrophenyl)-1H-1,2,4-triazole-3-sulfonamide
-
-
2-(2-chloroethoxy)-N-[(4,6-dimethoxypyrimidin-2-yl)carbamoyl]benzenesulfonamide
-
-
2-(2-chloroethoxy)-N-[(4,6-dimethylpyrimidin-2-yl)carbamoyl]benzenesulfonamide
-
-
2-chloro-3-oxocyclohex-1-en-1-yl-3-(trifluoromethyl)benzoate
-
2-chloro-5,5-dimethyl-3-oxocyclohex-1-en-1-yl 4-chlorobenzoic acid ester
-
2-chloro-6-methoxycarbonyl-5,5-dimethyl-3-oxocyclohex-1-en-1-yl 4-chlorobenzoate
-
2-chloro-N-([4-(methylamino)-6-[(1-methylethyl)sulfanyl]-1,3,5-triazin-2-yl]carbamoyl)benzenesulfonamide
-
-
2-chloro-N-[(4-methoxy-6-methyl-1,3,5-triazin-2-yl)carbamoyl]benzenesulfonamide
-
-
2-chloro-N-[[4-(ethylsulfanyl)-6-(methylamino)-1,3,5-triazin-2-yl]carbamoyl]benzenesulfonamide
-
-
2-chloro-N-[[4-(ethylsulfanyl)-6-methoxy-1,3,5-triazin-2-yl]carbamoyl]benzenesulfonamide
-
-
2-chloro-N-[[4-(ethylsulfanyl)-6-methylpyrimidin-2-yl]carbamoyl]benzenesulfonamide
-
-
2-chloro-N-[[4-(methylamino)-6-(methylsulfanyl)-1,3,5-triazin-2-yl]carbamoyl]benzenesulfonamide
-
-
2-chloro-N-[[4-methoxy-6-(methylsulfanyl)pyrimidin-2-yl]carbamoyl]benzenesulfonamide
-
-
2-chloro-N-[[4-methoxy-6-(propylsulfanyl)-1,3,5-triazin-2-yl]carbamoyl]benzenesulfonamide
-
-
2-chloro-N-[[4-methyl-6-(propylsulfanyl)pyrimidin-2-yl]carbamoyl]benzenesulfonamide
-
-
2-oxobutanoate
-
isoenzyme I has lower sensitivity to inhibition than isoenzyme III
2-phenyl-3-{[3-(trifluoromethyl)benzoyl]oxy}quinazolin-4-one
-
2-[(2-chloroethoxy)methyl]-N-[(4-chloropyrimidin-2-yl)carbamoyl]benzenesulfonamide
-
-
2-[(2-chloroethoxy)methyl]-N-[(4-methylpyrimidin-2-yl)carbamoyl]benzenesulfonamide
-
-
2-[[(4-chloro-6-methoxypyrimidin-2-yl)carbamoyl]sulfamoyl]-N,N-dimethylbenzamide
-
-
3-[(3-bromobenzoyl)oxy]-2-phenylquinazolin-4-one
-
3-[(4-nitrobenzoyl)oxy]quinazolin-4-one
-
5-bromo-2-([[(2-chlorophenyl)sulfonyl]carbamoyl]amino)pyrimidin-4-yl benzoate
-
-
branched-chain amino acids
-
feedback inhibition, differential inhibition of isozymes, overview
-
ethyl 2-([(4,6-dimethoxypyrimidin-2-yl)carbamoyl]sulfamoyl)benzoate
-
compound binds within a pocket of the enzyme formed by amino acid residues Met351, Asp375, Arg377, Gly509, Met570 and Val571
ethyl 2-([(4-chloro-6-methoxypyrimidin-2-yl)carbamoyl]sulfamoyl)benzoate
-
compound binds within a pocket of the enzyme formed by amino acid residues Met351, Asp375, Arg377, Gly509, Met570 and Val571
ethyl 2-([[5-bromo-4-(bromomethyl)pyrimidin-2-yl]carbamoyl]sulfamoyl)benzoate
-
-
ethyl 2-([[5-bromo-4-(ethoxymethyl)pyrimidin-2-yl]carbamoyl]sulfamoyl)benzoate
-
-
ethyl 2-([[5-bromo-4-(methoxymethyl)pyrimidin-2-yl]carbamoyl]sulfamoyl)benzoate
-
-
ethyl 2-[([4-[(acryloyloxy)methyl]-5-bromopyrimidin-2-yl]carbamoyl)sulfamoyl]benzoate
-
-
ethyl 2-[[(4-chloro-6-methoxypyrimidin-2-yl)carbamoyl]sulfamoyl]benzoate
-
-
ethyl 2-[[(5-bromo-4,6-dimethoxypyrimidin-2-yl)carbamoyl]sulfamoyl]benzoate
-
-
ethyl 2-[[(5-bromo-4,6-dimethylpyrimidin-2-yl)carbamoyl]sulfamoyl]benzoate
-
-
ethyl 2-[[(5-bromo-4-chloro-6-methoxypyrimidin-2-yl)carbamoyl]sulfamoyl]benzoate
-
-
Hydroxypyruvate
-
progressive inactivation of enzyme with kinetics of suicide inhibition, mechanism
imidazolinones
-
the imidazolinones behave as non-competitive or uncompetitive inhibitors
isoleucine
feedback inhibition; feedback inhibition; feedback inhibition
methyl 2-([[4-(ethylsulfanyl)-6-methoxypyrimidin-2-yl]carbamoyl]sulfamoyl)benzoate
-
-
methyl 2-([[4-(methylamino)-6-(propylsulfanyl)-1,3,5-triazin-2-yl]carbamoyl]sulfamoyl)benzoate
-
-
methyl 2-([[4-chloro-6-(methylamino)-1,3,5-triazin-2-yl]carbamoyl]sulfamoyl)benzoate
-
-
methyl 2-([[4-chloro-6-(methylsulfanyl)pyrimidin-2-yl]carbamoyl]sulfamoyl)benzoate
-
-
methyl 2-([[4-ethoxy-6-(methylamino)-1,3,5-triazin-2-yl]carbamoyl]sulfamoyl)benzoate
-
-
methyl 2-([[4-methoxy-6-(methylsulfanyl)pyrimidin-2-yl]carbamoyl]sulfamoyl)benzoate
-
-
methyl 2-([[4-methoxy-6-(propylsulfanyl)-1,3,5-triazin-2-yl]carbamoyl]sulfamoyl)benzoate
-
-
methyl 2-([[5-bromo-4-(bromomethyl)pyrimidin-2-yl]carbamoyl]sulfamoyl)benzoate
-
-
methyl 2-([[5-bromo-4-(dibromomethyl)pyrimidin-2-yl]carbamoyl]sulfamoyl)benzoate
-
-
methyl 2-([[5-bromo-4-(ethoxymethyl)pyrimidin-2-yl]carbamoyl]sulfamoyl)benzoate
-
-
methyl 2-([[5-bromo-4-(methoxymethyl)pyrimidin-2-yl]carbamoyl]sulfamoyl)benzoate
-
-
methyl 2-[[(4-methoxy-6-methyl-1,3,5-triazin-2-yl)carbamoyl]sulfamoyl]benzoate
-
-
N-([4-[(benzyloxy)methyl]-5-bromopyrimidin-2-yl]carbamoyl)-2-chlorobenzenesulfonamide
-
-
N-([5-bromo-4-[(prop-2-en-1-yloxy)methyl]pyrimidin-2-yl]carbamoyl)-2-(2-chloroethoxy)benzenesulfonamide
-
-
N-[(4-chloro-6-methoxypyrimidin-2-yl)carbamoyl]-2-nitrobenzenesulfonamide
-
-
N-[(5-bromo-4,6-dimethoxypyrimidin-2-yl)carbamoyl]-2-chlorobenzenesulfonamide
-
-
N-[(5-bromo-4,6-dimethoxypyrimidin-2-yl)carbamoyl]-2-nitrobenzenesulfonamide
-
-
N-[(5-bromo-4,6-dimethoxypyrimidin-2-yl)carbamoyl]-2-[(2-chloroethoxy)methyl]benzenesulfonamide
-
-
N-[(5-bromo-4,6-dimethylpyrimidin-2-yl)carbamoyl]-2-nitrobenzenesulfonamide
-
-
N-[(5-bromo-4,6-dimethylpyrimidin-2-yl)carbamoyl]-2-[(2-chloroethoxy)methyl]benzenesulfonamide
-
-
N-[(5-bromo-4-chloro-6-methoxypyrimidin-2-yl)carbamoyl]-2-chlorobenzenesulfonamide
-
-
N-[(5-bromo-4-chloro-6-methoxypyrimidin-2-yl)carbamoyl]-2-[(2-chloroethoxy)methyl]benzenesulfonamide
-
-
N-[(5-bromo-4-methoxypyrimidin-2-yl)carbamoyl]-2-nitrobenzenesulfonamide
-
-
N-[[5-bromo-4-(1-methylethoxy)pyrimidin-2-yl]carbamoyl]-2-nitrobenzenesulfonamide
-
-
N-[[5-bromo-4-(bromomethyl)pyrimidin-2-yl]carbamoyl]-2-nitrobenzenesulfonamide
-
-
N-[[5-bromo-4-(bromomethyl)pyrimidin-2-yl]carbamoyl]-2-[(2-chloroethoxy)methyl]benzenesulfonamide
-
-
N-[[5-bromo-4-(dibromomethyl)pyrimidin-2-yl]carbamoyl]-2-nitrobenzenesulfonamide
-
-
N-[[5-bromo-4-(dibromomethyl)pyrimidin-2-yl]carbamoyl]-2-[(2-chloroethoxy)methyl]benzenesulfonamide
-
-
N-[[5-bromo-4-(ethenyloxy)pyrimidin-2-yl]carbamoyl]-2-nitrobenzenesulfonamide
-
-
N-[[5-bromo-4-(ethoxymethyl)pyrimidin-2-yl]carbamoyl]-2-chlorobenzenesulfonamide
-
-
N-[[5-bromo-4-(ethoxymethyl)pyrimidin-2-yl]carbamoyl]-2-[(2-chloroethoxy)methyl]benzenesulfonamide
-
-
N-[[5-bromo-4-(methoxymethyl)pyrimidin-2-yl]carbamoyl]-2-chlorobenzenesulfonamide
-
-
N-[[5-bromo-4-(methoxymethyl)pyrimidin-2-yl]carbamoyl]-2-[(2-chloroethoxy)methyl]benzenesulfonamide
-
-
N-[[5-bromo-4-(tribromomethyl)pyrimidin-2-yl]carbamoyl]-2-nitrobenzenesulfonamide
-
-
sulfonylurea
-
the inhibition by sulfonylurea is non-competitive or nearly competitive with respect to pyruvate
[5-bromo-2-[([[2-(1-methoxyethenyl)phenyl]sulfonyl]carbamoyl)amino]pyrimidin-4-yl]methyl prop-2-enoate
-
-
Ile
-
isoenzyme AHS I is sensitive to feed-back inhibition, isoenzyme AHS II is insensitive
Leu
-
mixed noncompetitive inhibition of isoenzyme, pH-independent inhibition of isoenzyme III
Leu
-
isoenzyme AHS I is sensitive to feed-back inhibition, isoenzyme AHS II is insensitive
leucine
feedback inhibition; feedback inhibition; feedback inhibition
Val
-
isoenzyme AHS I is sensitive to feed-back inhibition, isoenzyme AHS II is insensitive
valine
feedback inhibition; feedback inhibition; feedback inhibition
additional information
-
inhibition kinetics or recombinant wild.type and reconstituted isozymes AHAS I
-
additional information
-
inhibitor synthesis, overview. Determination of ligand-receptor interaction and resistance mechanism in AHAS-sulfonylurea herbicide system, molecular modeling, overview
-
additional information
-
bulky substitutions in ortho-position of the sulfamoyl group in N-[(4-chloropyrimidin-2-yl)carbamoyl]benzenesulfonamide may enhance inhibitory activity. Negative charge distributed over a large surface area may enhance this activity. For better activity, the number of electronegative atoms present in the molecule should be high
-
additional information
P00892; P0ADG1
feedback inhibition takes place in the holoenzyme containing the regulatory and the catalytic subunits. The branched-chain amino acids are believed to bind only to the regulatory subunit and inhibit the enzyme. Certain imidazolinones show significant activity against the bacterial enzyme with Ki values of below 0.11 mM. Molecular docking of benzoyl ester compounds. AHAS-inhibitors and the probable binding pattern; feedback inhibition takes place in the holoenzyme containing the regulatory and the catalytic subunits. The branched-chain amino acids are believed to bind only to the regulatory subunit and inhibit the enzyme. Certain imidazolinones show significant activity against the bacterial enzyme with Ki values of below 0.11 mM. Molecular docking of benzoyl ester compounds. AHAS-inhibitors and the probable binding pattern; feedback inhibition takes place in the holoenzyme containing the regulatory and the catalytic subunits. The branched-chain amino acids are believed to bind only to the regulatory subunit and inhibit the enzyme. Certain imidazolinones show significant activity against the bacterial enzyme with Ki values of below 0.11 mM. Molecular docking of benzoyl ester compounds. AHAS-inhibitors and the probable binding pattern
-
additional information
feedback inhibition takes place in the holoenzyme containing the regulatory and the catalytic subunits. The branched-chain amino acids are believed to bind only to the regulatory subunit and inhibit the enzyme. Certain imidazolinones show significant activity against the bacterial enzyme with Ki values of below 0.11 mM. Molecular docking of benzoyl ester compounds. AHAS-inhibitors and the probable binding pattern; feedback inhibition takes place in the holoenzyme containing the regulatory and the catalytic subunits. The branched-chain amino acids are believed to bind only to the regulatory subunit and inhibit the enzyme. Certain imidazolinones show significant activity against the bacterial enzyme with Ki values of below 0.11 mM. Molecular docking of benzoyl ester compounds. AHAS-inhibitors and the probable binding pattern; feedback inhibition takes place in the holoenzyme containing the regulatory and the catalytic subunits. The branched-chain amino acids are believed to bind only to the regulatory subunit and inhibit the enzyme. Certain imidazolinones show significant activity against the bacterial enzyme with Ki values of below 0.11 mM. Molecular docking of benzoyl ester compounds. AHAS-inhibitors and the probable binding pattern
-
additional information
feedback inhibition takes place in the holoenzyme containing the regulatory and the catalytic subunits. The branched-chain amino acids are believed to bind only to the regulatory subunit and inhibit the enzyme. Certain imidazolinones show significant activity against the bacterial enzyme with Ki values of below 0.11 mM. Molecular docking of benzoyl ester compounds. AHAS-inhibitors and the probable binding pattern; feedback inhibition takes place in the holoenzyme containing the regulatory and the catalytic subunits. The branched-chain amino acids are believed to bind only to the regulatory subunit and inhibit the enzyme. Certain imidazolinones show significant activity against the bacterial enzyme with Ki values of below 0.11 mM. Molecular docking of benzoyl ester compounds. AHAS-inhibitors and the probable binding pattern; feedback inhibition takes place in the holoenzyme containing the regulatory and the catalytic subunits. The branched-chain amino acids are believed to bind only to the regulatory subunit and inhibit the enzyme. Certain imidazolinones show significant activity against the bacterial enzyme with Ki values of below 0.11 mM. Molecular docking of benzoyl ester compounds. AHAS-inhibitors and the probable binding pattern
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
2.9
pyruvate
-
fusion protein containing an N-terminal oligohistidine sequence on the large subunit
additional information
additional information
-
kinetics or recombinant wild-type and reconstituted isozymes AHAS I, exclusive binding model
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
47.4
pyruvate
-
fusion protein containing an N-terminal oligohistidine sequence on the large subunit
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.006
(5-bromo-2-[[([2-[(2-chloroethoxy)methyl]phenyl]sulfonyl)carbamoyl]amino]pyrimidin-4-yl)methyl benzoate
Escherichia coli
-
pH 7.5, 22°C
0.00484
(5-bromo-2-[[([2-[(2-chloroethoxy)methyl]phenyl]sulfonyl)carbamoyl]amino]pyrimidin-4-yl)methyl phenylacetate
Escherichia coli
-
pH 7.5, 22°C
0.00584
(5-bromo-2-[[([2-[(2-chloroethoxy)methyl]phenyl]sulfonyl)carbamoyl]amino]pyrimidin-4-yl)methyl prop-2-enoate
Escherichia coli
-
pH 7.5, 22°C
0.021
1-(4,6-dimethoxypyrimidin-2-yl)-5-methoxymethyl-N-(2-isopropyl-6-nitrophenyl)-1H-1,2,4-triazole-3-sulfonamide
Escherichia coli
-
pH 7.6, 37°C
0.022
1-(4,6-dimethoxypyrimidin-2-yl)-5-methyl-N-(2-isopropyl-6-nitrophenyl)-1H-1,2,4-triazole-3-sulfonamide
Escherichia coli
-
pH 7.6, 37°C
0.032
1-(4,6-dimethoxypyrimidin-2-yl)-5-methylthio-N-(2-chloro-6-fluorophenyl)-1H-1,2,4-triazole-3-sulfonamide
Escherichia coli
-
pH 7.6, 37°C
0.03
1-(4-chloro-6-methoxypyrimidin-2-yl)-5-methoxy-N-(2-methyl-6-nitrophenyl)-1H-1,2,4-triazole-3-sulfonamide
Escherichia coli
-
pH 7.6, 37°C
0.00746
2-(2-chloroethoxy)-N-[(4,6-dimethoxypyrimidin-2-yl)carbamoyl]benzenesulfonamide
Escherichia coli
-
pH 7.5, 22°C
0.00452
2-(2-chloroethoxy)-N-[(4,6-dimethylpyrimidin-2-yl)carbamoyl]benzenesulfonamide
Escherichia coli
-
pH 7.5, 22°C
0.00529
2-chloro-N-([4-(methylamino)-6-[(1-methylethyl)sulfanyl]-1,3,5-triazin-2-yl]carbamoyl)benzenesulfonamide
Escherichia coli
-
pH 7.5, 22°C
0.00693
2-chloro-N-[(4,6-dimethoxypyrimidin-2-yl)carbamoyl]benzenesulfonamide
Escherichia coli
-
pH 7.5, 22°C
0.00471
2-chloro-N-[(4,6-dimethylpyrimidin-2-yl)carbamoyl]benzenesulfonamide
Escherichia coli
-
pH 7.5, 22°C
0.00649
2-chloro-N-[(4-methoxy-6-methyl-1,3,5-triazin-2-yl)carbamoyl]benzenesulfonamide
Escherichia coli
-
pH 7.5, 22°C
0.00541
2-chloro-N-[[4-(ethylsulfanyl)-6-(methylamino)-1,3,5-triazin-2-yl]carbamoyl]benzenesulfonamide
Escherichia coli
-
pH 7.5, 22°C
0.00369
2-chloro-N-[[4-(ethylsulfanyl)-6-methoxy-1,3,5-triazin-2-yl]carbamoyl]benzenesulfonamide
Escherichia coli
-
pH 7.5, 22°C
0.00442
2-chloro-N-[[4-(ethylsulfanyl)-6-methylpyrimidin-2-yl]carbamoyl]benzenesulfonamide
Escherichia coli
-
pH 7.5, 22°C
0.00525
2-chloro-N-[[4-(methylamino)-6-(methylsulfanyl)-1,3,5-triazin-2-yl]carbamoyl]benzenesulfonamide
Escherichia coli
-
pH 7.5, 22°C
0.00556
2-chloro-N-[[4-methoxy-6-(methylsulfanyl)pyrimidin-2-yl]carbamoyl]benzenesulfonamide
Escherichia coli
-
pH 7.5, 22°C
0.00355
2-chloro-N-[[4-methoxy-6-(propylsulfanyl)-1,3,5-triazin-2-yl]carbamoyl]benzenesulfonamide
Escherichia coli
-
pH 7.5, 22°C
0.00352
2-chloro-N-[[4-methyl-6-(propylsulfanyl)pyrimidin-2-yl]carbamoyl]benzenesulfonamide
Escherichia coli
-
pH 7.5, 22°C
0.00531
2-[(2-chloroethoxy)methyl]-N-[(4-chloropyrimidin-2-yl)carbamoyl]benzenesulfonamide
Escherichia coli
-
pH 7.5, 22°C
0.00533
2-[(2-chloroethoxy)methyl]-N-[(4-methylpyrimidin-2-yl)carbamoyl]benzenesulfonamide
Escherichia coli
-
pH 7.5, 22°C
0.00712
2-[[(4-chloro-6-methoxypyrimidin-2-yl)carbamoyl]sulfamoyl]-N,N-dimethylbenzamide
Escherichia coli
-
pH 7.5, 22°C
0.00571
5-bromo-2-([[(2-chlorophenyl)sulfonyl]carbamoyl]amino)pyrimidin-4-yl benzoate
Escherichia coli
-
pH 7.5, 22°C
0.0078
ethyl 2-([[5-bromo-4-(bromomethyl)pyrimidin-2-yl]carbamoyl]sulfamoyl)benzoate
Escherichia coli
-
pH 7.5, 22°C
0.00651
ethyl 2-([[5-bromo-4-(ethoxymethyl)pyrimidin-2-yl]carbamoyl]sulfamoyl)benzoate
Escherichia coli
-
pH 7.5, 22°C
0.0067
ethyl 2-([[5-bromo-4-(methoxymethyl)pyrimidin-2-yl]carbamoyl]sulfamoyl)benzoate
Escherichia coli
-
pH 7.5, 22°C
0.00711
ethyl 2-[([4-[(acryloyloxy)methyl]-5-bromopyrimidin-2-yl]carbamoyl)sulfamoyl]benzoate
Escherichia coli
-
pH 7.5, 22°C
0.0092
ethyl 2-[[(4,6-dimethoxypyrimidin-2-yl)carbamoyl]sulfamoyl]benzoate
Escherichia coli
-
pH 7.5, 22°C
0.0061
ethyl 2-[[(4,6-dimethylpyrimidin-2-yl)carbamoyl]sulfamoyl]benzoate
Escherichia coli
-
pH 7.5, 22°C
0.00834
ethyl 2-[[(4-chloro-6-methoxypyrimidin-2-yl)carbamoyl]sulfamoyl]benzoate
Escherichia coli
-
pH 7.5, 22°C
0.00709
ethyl 2-[[(4-chloro-6-methylpyrimidin-2-yl)carbamoyl]sulfamoyl]benzoate
Escherichia coli
-
pH 7.5, 22°C
0.00669
ethyl 2-[[(4-methylpyrimidin-2-yl)carbamoyl]sulfamoyl]benzoate
Escherichia coli
-
pH 7.5, 22°C
0.00703
ethyl 2-[[(5-bromo-4,6-dimethoxypyrimidin-2-yl)carbamoyl]sulfamoyl]benzoate
Escherichia coli
-
pH 7.5, 22°C
0.00678
ethyl 2-[[(5-bromo-4,6-dimethylpyrimidin-2-yl)carbamoyl]sulfamoyl]benzoate
Escherichia coli
-
pH 7.5, 22°C
0.0068
ethyl 2-[[(5-bromo-4-chloro-6-methoxypyrimidin-2-yl)carbamoyl]sulfamoyl]benzoate
Escherichia coli
-
pH 7.5, 22°C
0.00458
methyl 2-([[4-(ethylsulfanyl)-6-methoxypyrimidin-2-yl]carbamoyl]sulfamoyl)benzoate
Escherichia coli
-
pH 7.5, 22°C
0.00733
methyl 2-([[4-(methylamino)-6-(propylsulfanyl)-1,3,5-triazin-2-yl]carbamoyl]sulfamoyl)benzoate
Escherichia coli
-
pH 7.5, 22°C
0.00686
methyl 2-([[4-chloro-6-(methylamino)-1,3,5-triazin-2-yl]carbamoyl]sulfamoyl)benzoate
Escherichia coli
-
pH 7.5, 22°C
0.00631
methyl 2-([[4-chloro-6-(methylsulfanyl)pyrimidin-2-yl]carbamoyl]sulfamoyl)benzoate
Escherichia coli
-
pH 7.5, 22°C
0.00786
methyl 2-([[4-ethoxy-6-(methylamino)-1,3,5-triazin-2-yl]carbamoyl]sulfamoyl)benzoate
Escherichia coli
-
pH 7.5, 22°C
0.00646
methyl 2-([[4-methoxy-6-(methylsulfanyl)pyrimidin-2-yl]carbamoyl]sulfamoyl)benzoate
Escherichia coli
-
pH 7.5, 22°C
0.00474
methyl 2-([[4-methoxy-6-(propylsulfanyl)-1,3,5-triazin-2-yl]carbamoyl]sulfamoyl)benzoate
Escherichia coli
-
pH 7.5, 22°C
0.00415
methyl 2-([[5-bromo-4-(bromomethyl)pyrimidin-2-yl]carbamoyl]sulfamoyl)benzoate
Escherichia coli
-
pH 7.5, 22°C
0.00482
methyl 2-([[5-bromo-4-(dibromomethyl)pyrimidin-2-yl]carbamoyl]sulfamoyl)benzoate
Escherichia coli
-
pH 7.5, 22°C
0.00461
methyl 2-([[5-bromo-4-(ethoxymethyl)pyrimidin-2-yl]carbamoyl]sulfamoyl)benzoate
Escherichia coli
-
pH 7.5, 22°C
0.00605
methyl 2-([[5-bromo-4-(methoxymethyl)pyrimidin-2-yl]carbamoyl]sulfamoyl)benzoate
Escherichia coli
-
pH 7.5, 22°C
0.0071
methyl 2-[[(4-methoxy-6-methyl-1,3,5-triazin-2-yl)carbamoyl]sulfamoyl]benzoate
Escherichia coli
-
pH 7.5, 22°C
0.00571
methyl 2-[[(4-methylpyrimidin-2-yl)carbamoyl]sulfamoyl]benzoate
Escherichia coli
-
pH 7.5, 22°C
0.00453
methyl 2-[[(5-bromo-4-methylpyrimidin-2-yl)carbamoyl]sulfamoyl]benzoate
Escherichia coli
-
pH 7.5, 22°C
0.0046
N-([4-[(benzyloxy)methyl]-5-bromopyrimidin-2-yl]carbamoyl)-2-chlorobenzenesulfonamide
Escherichia coli
-
pH 7.5, 22°C
0.00531
N-([5-bromo-4-[(prop-2-en-1-yloxy)methyl]pyrimidin-2-yl]carbamoyl)-2-(2-chloroethoxy)benzenesulfonamide
Escherichia coli
-
pH 7.5, 22°C
0.008
N-[(4,6-dimethoxypyrimidin-2-yl)carbamoyl]-2-nitrobenzenesulfonamide
Escherichia coli
-
pH 7.5, 22°C
0.00769
N-[(4-chloro-6-methoxypyrimidin-2-yl)carbamoyl]-2-nitrobenzenesulfonamide
Escherichia coli
-
pH 7.5, 22°C
0.00523
N-[(4-methylpyrimidin-2-yl)carbamoyl]-2-nitrobenzenesulfonamide
Escherichia coli
-
pH 7.5, 22°C
0.00552
N-[(5-bromo-4,6-dimethoxypyrimidin-2-yl)carbamoyl]-2-chlorobenzenesulfonamide
Escherichia coli
-
pH 7.5, 22°C
0.0053
N-[(5-bromo-4,6-dimethoxypyrimidin-2-yl)carbamoyl]-2-nitrobenzenesulfonamide
Escherichia coli
-
pH 7.5, 22°C
0.00545
N-[(5-bromo-4,6-dimethoxypyrimidin-2-yl)carbamoyl]-2-[(2-chloroethoxy)methyl]benzenesulfonamide
Escherichia coli
-
pH 7.5, 22°C
0.0048
N-[(5-bromo-4,6-dimethylpyrimidin-2-yl)carbamoyl]-2-nitrobenzenesulfonamide
Escherichia coli
-
pH 7.5, 22°C
0.00488
N-[(5-bromo-4,6-dimethylpyrimidin-2-yl)carbamoyl]-2-[(2-chloroethoxy)methyl]benzenesulfonamide
Escherichia coli
-
pH 7.5, 22°C
0.00478
N-[(5-bromo-4-chloro-6-methoxypyrimidin-2-yl)carbamoyl]-2-chlorobenzenesulfonamide
Escherichia coli
-
pH 7.5, 22°C
0.00477
N-[(5-bromo-4-chloro-6-methoxypyrimidin-2-yl)carbamoyl]-2-[(2-chloroethoxy)methyl]benzenesulfonamide
Escherichia coli
-
pH 7.5, 22°C
0.00508
N-[(5-bromo-4-methoxypyrimidin-2-yl)carbamoyl]-2-nitrobenzenesulfonamide
Escherichia coli
-
pH 7.5, 22°C
0.00553
N-[(5-bromo-4-methylpyrimidin-2-yl)carbamoyl]-2-nitrobenzenesulfonamide
Escherichia coli
-
pH 7.5, 22°C
0.00388
N-[(5-bromopyrimidin-2-yl)carbamoyl]-2-chlorobenzenesulfonamide
Escherichia coli
-
pH 7.5, 22°C
0.0044
N-[[5-bromo-4-(1-methylethoxy)pyrimidin-2-yl]carbamoyl]-2-nitrobenzenesulfonamide
Escherichia coli
-
pH 7.5, 22°C
0.00516
N-[[5-bromo-4-(bromomethyl)pyrimidin-2-yl]carbamoyl]-2-nitrobenzenesulfonamide
Escherichia coli
-
pH 7.5, 22°C
0.00669
N-[[5-bromo-4-(bromomethyl)pyrimidin-2-yl]carbamoyl]-2-[(2-chloroethoxy)methyl]benzenesulfonamide
Escherichia coli
-
pH 7.5, 22°C
0.00503
N-[[5-bromo-4-(dibromomethyl)pyrimidin-2-yl]carbamoyl]-2-nitrobenzenesulfonamide
Escherichia coli
-
pH 7.5, 22°C
0.00697
N-[[5-bromo-4-(dibromomethyl)pyrimidin-2-yl]carbamoyl]-2-[(2-chloroethoxy)methyl]benzenesulfonamide
Escherichia coli
-
pH 7.5, 22°C
0.0036
N-[[5-bromo-4-(ethenyloxy)pyrimidin-2-yl]carbamoyl]-2-nitrobenzenesulfonamide
Escherichia coli
-
pH 7.5, 22°C
0.00427
N-[[5-bromo-4-(ethoxymethyl)pyrimidin-2-yl]carbamoyl]-2-chlorobenzenesulfonamide
Escherichia coli
-
pH 7.5, 22°C
0.00514
N-[[5-bromo-4-(ethoxymethyl)pyrimidin-2-yl]carbamoyl]-2-[(2-chloroethoxy)methyl]benzenesulfonamide
Escherichia coli
-
pH 7.5, 22°C
0.00566
N-[[5-bromo-4-(methoxymethyl)pyrimidin-2-yl]carbamoyl]-2-chlorobenzenesulfonamide
Escherichia coli
-
pH 7.5, 22°C
0.00617
N-[[5-bromo-4-(methoxymethyl)pyrimidin-2-yl]carbamoyl]-2-[(2-chloroethoxy)methyl]benzenesulfonamide
Escherichia coli
-
pH 7.5, 22°C
0.0058
N-[[5-bromo-4-(tribromomethyl)pyrimidin-2-yl]carbamoyl]-2-nitrobenzenesulfonamide
Escherichia coli
-
pH 7.5, 22°C
0.00503
[5-bromo-2-[([[2-(1-methoxyethenyl)phenyl]sulfonyl]carbamoyl)amino]pyrimidin-4-yl]methyl prop-2-enoate
Escherichia coli
-
pH 7.5, 22°C
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
20
20.9
-
wild-type AHAS III, truncated regulatory subunit ilvH-DELTA 86, pH 7.6, 37°C
32
-
catalytic subunit ilvB, truncated regulatory subunit ilvB-DELTA86, 37°C, pH 7.6
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.5
7.6
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
isoenzyme I and III are expressed in wild type cells, isoenzyme II is cryptic
-
-
large and small subunit of isozyme 1 encoded by genes ilvB and ilvN; isozyme AHAS I, Escherichia coli wild-type does not contain AHAS II as result of a frameshift mutation, leading to a premature stop codon in the centre of the catalytic subunit of gene ilvG, which results into a cryptic form of AHAS II found in strain K-12, normal expression can be restored by gene ilvO mutation
UniProt
large and small subunit of isozyme 2 encoded by genes ilvG and ilvM; isozyme AHAS I, Escherichia coli wild-type does not contain AHAS II as result of a frameshift mutation, leading to a premature stop codon in the centre of the catalytic subunit of gene ilvG, which results into a cryptic form of AHAS II found in strain K-12, normal expression can be restored by gene ilvO mutation
P00892; P0ADG1
UniProt
large and small subunit of isozyme 3 encoded by genes ilvI and ilvH; isozyme AHAS I, Escherichia coli wild-type does not contain AHAS II as result of a frameshift mutation, leading to a premature stop codon in the centre of the catalytic subunit of gene ilvG, which results into a cryptic form of AHAS II found in strain K-12, normal expression can be restored by gene ilvO mutation
UniProt
wild type and two isogenic strains PS1035, containing only acetohydroxy acid synthase III, and strain PS1036, containing only acetohydroxy acid synthase I
-
-
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
three types of isozymes, AHAS I, II, III, are found in Enterobacteria encoded by ilvBN, ilvGMEDA, ilvIH operons, respectively. Bacterial AHAS consists of a regulatory and a catalytic subunit
malfunction
enzyme inhibition abolishes biosynthesis of brachend chain amino acids and leads to bacteriostasis
metabolism
the bacterial anabolic enzyme form catalyzes the first step in biosynthesis of branched amino acids isoleucine, leucine and valine. It catalyzes the first and the most crucial step which is either the self condensation of pyruvate to form 2-acetolactate or the condensation between lactate and 2-oxobutyrate to form 2-aceto-2-hydroxybutyrate. 2-acetolactate and 2-aceto-2-hydroxybutyrate serve as the precursors for the synthesis of leucine and valine while latter serves as the precursor for the synthesis of isoleucine. In some bacteria, the enzyme is responsible for the formation of butanediol and other products of fermentation
additional information
additional information
P00892; P0ADG1
there exist two types of the enzyme, catabolic and anabolic AHAS. The anabolic form of the enzyme consists of two subunits out of which one is catalytic while the other is regulatory in nature. The regulatory subunit acts via feedback inhibition
additional information
there exist two types of the enzyme, catabolic and anabolic AHAS. The anabolic form of the enzyme consists of two subunits out of which one is catalytic while the other is regulatory in nature. The regulatory subunit acts via feedback inhibition
additional information
there exist two types of the enzyme, catabolic and anabolic AHAS. The anabolic form of the enzyme consists of two subunits out of which one is catalytic while the other is regulatory in nature. The regulatory subunit acts via feedback inhibition
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). PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
130000
-
sucrose density gradient sedimentation, glycerol density gradient sedimentation
60000
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
tetramer
the enzyme consists of a large catalytic and a small regulatory subunit, two copies of which form the enzyme tetramer
additional information
dimer
-
1 * 59000-66000, catalytic subunit + 1 * 10000-20000, above, regulatory subunit
additional information
-
enzymes in the AHAS family generally consist of regulatory and catalytic subunits, subunit composition, dimeric structure analysis of the regulatory subunit of isozyme AHAS III, overview
additional information
-
pairs of catalytic subunits form an intimate dimer containing two active sites, each of which lies across a dimer interface and involves both monomers, the catalytic subunit of AHAS II is not active alone
additional information
-
by mapping the 3D contour maps of CoMFA and CoMSIA models into the possible inhibitory active site in the crystal structure of catalytic subunit of yeast AHAS, a plausible binding model for AHAS, with best fit QSAR in the literature so far, is proposed
additional information
-
isozyme AHAS I, catalytic subunit ilvB, regulatory subunit ilvN. AHAS II, catalytic subunit ilvG, regulatory subunit ilvM. Isozyme AHAS III, catalytic subunit ilvI, regulatory subunit ilvH. AHAS II regulatory subunit ilvM is able to activate the catalytic subunits of all three of the isozymes, and the truncated AHAS III regulatory subunits ilvH-DELTA80, ilvH-DELTA86 and ilvH-DELTA89 are able to activate the catalytic subunits of both AHAS I and AHAS III. Contrary to wild-type, none of the heterologously activated enzymes have any feedback sensitivity
additional information
-
the regulatory subunit possesses no AHAS activity but greatly stimulates the activity of the catalytic subunit, it is necessary for AHAS to be inhibited by branched-chain amino acids, structures of catalytic and regulatory subunits, sequence comparisons, overview
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
purified recombinant wild-type and selenomethionine-labeled isozyme AHAS III in complex with valine, hanging drop vapour diffusion method, room temperature, 0.0036 ml of protein solution containing 10-25 mg/ml protein and 0.5 M MgCl2, is mixed with reservoir solution containing 30-40% PEG 400, 0.4-0.6 M MgCl2, 100 mM Tris-HCl, pH 8.5, tetragonal or orthorhombic crystals, X-ray diffraction structure determination and analysis at 1.75-2.5 A resolution
-
solution NMR studies. The secondary structure of the FAD binding domain of large subunit ilvB is similar to the structure of this domain in the catalytic subunit of yeast AHAS. The regulatory subunit ilvN interacts with ilvBalpha and ilvBbeta domains of the catalytic subunit and not with the ilvBgamma domain. ilvN binds close to the FAD binding site in ilvBbeta and proximal to the intrasubunit ilvBalpha/ilvBbeta domain interface
-
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
A36V
-
site-directed mutagenesis of the regulatory subunit, the mutant is resistant to inhibition by valine
E47A
E47Q
F109M
-
both substrate affinity and kcat are significantly compromised. The specificity for 2-ketobutyrate as acceptor is not altered
G14A
-
site-directed mutagenesis of the regulatory subunit, the mutant is resistant to inhibition by valine
G14D
-
site-directed mutagenesis of the regulatory subunit, the mutant is resistant to inhibition by valine
L131R
-
site-directed mutagenesis of the regulatory subunit, the mutant is resistant to inhibition by valine
L16A
-
site-directed mutagenesis of the regulatory subunit, the mutant shows increased sensitivity to valine inhibition compared to the wild-type subunit
L9A
-
site-directed mutagenesis of the regulatory subunit, the mutant shows slightly decreased sensitivity to valine inhibition compared to the wild-type subunit
L9H
-
site-directed mutagenesis of the regulatory subunit, the mutant is resistant to inhibition by valine
L9V
-
site-directed mutagenesis of the regulatory subunit, the mutant shows slightly decreased sensitivity to valine inhibition compared to the wild-type subunit
N11A
-
site-directed mutagenesis of the regulatory subunit, the mutant is resistant to inhibition by valine
N11D
-
site-directed mutagenesis of the regulatory subunit, the mutant shows highly decreased sensitivity to valine inhibition compared to the wild-type subunit
N11H
-
site-directed mutagenesis of the regulatory subunit, the mutant shows highly decreased sensitivity to valine inhibition compared to the wild-type subunit
N29D
-
site-directed mutagenesis of the regulatory subunit, the mutant shows highly decreased sensitivity to valine inhibition compared to the wild-type subunit
N29H
-
site-directed mutagenesis of the regulatory subunit, the mutant shows highly decreased sensitivity to valine inhibition compared to the wild-type subunit
T34C
-
site-directed mutagenesis of the regulatory subunit, the mutant shows decreased sensitivity to valine inhibition compared to the wild-type subunit
T34I
-
site-directed mutagenesis of the regulatory subunit, the mutant shows highly decreased sensitivity to valine inhibition compared to the wild-type subunit
T47C
-
site-directed mutagenesis of the regulatory subunit, the mutant shows decreased sensitivity to valine inhibition compared to the wild-type subunit
V153D
-
site-directed mutagenesis of the regulatory subunit, the mutant is resistant to inhibition by valine
V35A
-
site-directed mutagenesis of the regulatory subunit, the mutant shows decreased sensitivity to valine inhibition compared to the wild-type subunit
V375A
V375I
-
slightly reduced kcat value with a moderate increase of the apparent KM of pyruvate. The specificity for 2-ketobutyrate as acceptor is not altered
W464L
additional information
V375A
-
mutation in isozyme AHAS II, allows 2-oxo-butanoate to be a good first substrate and the mutant enzyme can synthesize 2-propionyl-2-hydroxybutanoate
V375A
-
slightly reduced kcat value with a moderate increase of the apparent KM of pyruvate. The specificity for 2-ketobutyrate as acceptor is not altered
W464L
-
the mutant of isozyme AHAS II has lost the preference for 2-ketobutyrate as second substrate
additional information
-
isozyme AHAS II mutants of residues Phe109, Met250, Arg276 and Trp464 are nearly inactive in (S)-2-acetolactate formation, but show increased activity with pyruvate and benzaldehyde compared to the wild-type isozyme
additional information
-
the truncated mutant DELTA80 is resistant to inhibition by valine
additional information
-
identification and phenotypes of herbicide-resistant mutant enzymes, overview
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
45
-
15 min, 69% loss of activity, isoenzyme I, slight stimulation of activity of isoenzyme III
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
dialysis causes 38% loss of activity of isoenzyme I, stimulates activity of isoenzyme III
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant His-tagged isozyme I holoenzyme or individual subunits from strain BL21 by affinity chromatography
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression is considerably higher from a vector that introduces a 50 residue N-terminal fusion containing an oligohistidine sequence on the large subunit
-
gene ilvH, encoding the regulatory subunit SSU, expression of wild-type and mutants, and of the selenomethionine variant
-
isozyme I subunit-encoding genes ilvB and ilvN, DNA and amino acid sequence determination and analysis, expression of His-tagged holoenzyme or individual subunits in strain BL21
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
RENATURED/Commentary
ORGANISM
UNIPROT
LITERATURE
reconstitution of the holoenzyme from recombinant small and large subunits, not highly dependent on MgCl2, but when no extraneous magnesium is added the enzyme does not reach its full potential for activity
-
reconstitution of the holoenzyme from recombinantly expressed, purified subunits encoded by genes ilvB and ilvN
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
drug development
drug development
the enzyme is a target for drug development
drug development
-
AHAS is the target of the sulfonylurea and imidazolinone herbicides
drug development
-
the enzyme is the target of several herbicides, sulfonylureas, imidazolinones and other herbicides, structures of inhibitor-enzyme complexes explain the herbicide-enzyme interaction
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Barak, Z.; Chipman, D.M.; Gollop, N.
Physiological implications of the specificity of acetohydroxy acid synthase isozymes of enteric bacteria
J. Bacteriol.
169
3750-3756
1987
Escherichia coli, Salmonella enterica subsp. enterica serovar Typhimurium
Eoyang, L.; Silverman, P.M.
Purification and subunit composition of acetohydroxyacid synthase I from Escherichia coli K-12
J. Bacteriol.
157
184-189
1984
Escherichia coli
Gollop, N.; Chipman, D.M.; Barak, Z.
Inhibition of acetohydroxy acid synthase by leucine
Biochim. Biophys. Acta
748
34-39
1983
Escherichia coli
DeFelice, M.; Lago, C.T.; Squires, C.H.; Calvo, J.M.
Acetohydroxy acid synthase isoenzymes of Escherichia coli K12 and Salmonella typhimurium
Ann. Microbiol.
133A
251-256
1982
Escherichia coli, Salmonella enterica subsp. enterica serovar Typhimurium
-
Grimminger, H.; Umbarger, H.E.
Acetohydroxy acid synthase I of Escherichia coli: purification and properties
J. Bacteriol.
137
846-853
1979
Escherichia coli
DeFelice, M.; Squires, C.; Levinthal, M.
A comparative study of the acetohydroxy acid synthase isoenzymes of Escherichia coli K-12
Biochim. Biophys. Acta
541
9-17
1978
Escherichia coli
-
Blatt, J.M.; Pledger, W.J.; Umbarger, H.E.
Isoleucine and valine metabolism in Escherichia coli. XX. Multiple forms of acetohydroxy acid synthetase
Biochem. Biophys. Res. Commun.
48
444-450
1972
Escherichia coli
Squires, C.H.; DeFelice, M.; Devereux, J.; Calvo, J.M.
Molecular structure of ilvIH and its evolutionary relationship to ilvG in Escherichia coli K12
Nucleic Acids Res.
11
5299-5313
1983
Escherichia coli
Hill, C.H.; Pang, S.S.; Duggleby, R.G.
Purification of Escherichia coli acetohydroxyacid synthase isoenzyme II and reconstitution of active enzyme from its individual pure subunits
Biochem. J.
327
891-898
1997
Escherichia coli
Eoyang, L.; Silverman, P.M.
Purification and assays of acetolactate synthase I from Escherichia coli K-12
Methods Enzymol.
166
435-445
1988
Escherichia coli
Bar-Ilan, A.; Balan, V.; Tittmann, K.; Golbik, R.; Vyazmensky, M.; Hubner, G.; Barak, Z.; Chipman, D.M.
Binding and activation of thiamin diphosphate in acetohydroxyacid synthase
Biochemistry
40
11946-11954
2001
Escherichia coli
Duggleby, R.G.
Suicide inhibition of acetohydroxyacid synthase by hydroxypyruvate
J. Enzyme Inhib. Med. Chem.
20
1-4
2005
Escherichia coli
Tittmann, K.; Vyazmensky, M.; Hubner, G.; Barak, Z.; Chipman, D.M.
The carboligation reaction of acetohydroxyacid synthase II: steady-state intermediate distributions in wild type and mutants by NMR
Proc. Natl. Acad. Sci. USA
102
553-558
2005
Escherichia coli
Vinogradov, M.; Kaplun, A.; Vyazmensky, M.; Engel, S.; Golbik, R.; Tittmann, K.; Uhlemann, K.; Meshalkina, L.; Barak, Z.; Huebner, G.; Chipman, D.M.
Monitoring the acetohydroxy acid synthase reaction and related carboligations by circular dichroism spectroscopy
Anal. Biochem.
342
126-133
2005
Escherichia coli
Vinogradov, V.; Vyazmensky, M.; Engel, S.; Belenky, I.; Kaplun, A.; Kryukov, O.; Barak, Z.; Chipman, D.M.
Acetohydroxyacid synthase isozyme I from Escherichia coli has unique catalytic and regulatory properties
Biochim. Biophys. Acta
1760
356-363
2006
Escherichia coli
Chipman, D.M.; Duggleby, R.G.; Tittmann, K.
Mechanisms of acetohydroxyacid synthases
Curr. Opin. Chem. Biol.
10
88
2006
Escherichia coli
-
Kaplun, A.; Vyazmensky, M.; Zherdev, Y.; Belenky, I.; Slutzker, A.; Mendel, S.; Barak, Z.; Chipman, D.M.; Shaanan, B.
Structure of the regulatory subunit of acetohydroxyacid synthase isozyme III from Escherichia coli
J. Mol. Biol.
357
951-963
2006
Escherichia coli
McCourt, J.A.; Duggleby, R.G.
How an enzyme answers multiple-choice questions
Trends Biochem. Sci.
30
222-225
2005
Escherichia coli, Saccharomyces cerevisiae (P07342)
Vyazmensky, M.; Zherdev, Y.; Slutzker, A.; Belenky, I.; Kryukov, O.; Barak, Z.; Chipman, D.M.
Interactions between large and small subunits of different acetohydroxyacid synthase isozymes of Escherichia coli
Biochemistry
48
8731-8737
2009
Escherichia coli
Yu, Z.; Niu, C.; Ban, S.; Wen, X.; Xi, Z.
Study on structure-activity relationship of mutation-dependent herbicide resistance acetohydroxyacid synthase through 3D-QSAR and mutation
Chin. Sci. Bull.
52
1929-1941
2007
Escherichia coli
-
Chipman, D.; Barak, Z.; Shaanan, B.; Vyazmensky, M.; Binshtein, E.; Belenky, I.; Temam, V.; Steinmetz, A.; Golbik, R.; Tittmann, K.
Origin of the specificities of acetohydroxyacid synthases and glyoxylate carboligase
J. Mol. Catal. B
61
50-55
2009
Escherichia coli
-
Megha Karanth, N.; Mitra, A.; Sarma, S.
Solution NMR studies of acetohydroxy acid synthase I: Identification of the sites of inter-subunit interactions using multidimensional NMR methods
J. Mol. Catal. B
61
7-13
2009
Escherichia coli
-
Roy, K.; Paul, S.
Docking and 3D-QSAR studies of acetohydroxy acid synthase inhibitor sulfonylurea derivatives
J. Mol. Model.
16
951-964
2009
Escherichia coli
Duggleby, R.G.; McCourt, J.A.; Guddat, L.W.
Structure and mechanism of inhibition of plant acetohydroxyacid synthase
Plant Physiol. Biochem.
46
309-324
2008
Arabidopsis thaliana, Brassica napus, Escherichia coli, Helianthus annuus, Nicotiana tabacum, Nitrosomonas europaea, Salmonella enterica subsp. enterica serovar Typhimurium, Thermotoga maritima, Saccharomyces cerevisiae (P07342), Gossypium hirsutum (Q42768)
Steinmetz, A.; Vyazmensky, M.; Meyer, D.; Barak, Z.E.; Golbik, R.; Chipman, D.M.; Tittmann, K.
Valine 375 and phenylalanine 109 confer affinity and specificity for pyruvate as donor substrate in acetohydroxy acid synthase isozyme II from Escherichia coli
Biochemistry
49
5188-5199
2010
Escherichia coli
Vyazmensky, M.; Steinmetz, A.; Meyer, D.; Golbik, R.; Barak, Z.; Tittmann, K.; Chipman, D.M.
Significant catalytic roles for Glu47 and Gln 110 in all four of the C-C bond-making and -breaking steps of the reactions of acetohydroxyacid synthase II
Biochemistry
50
3250-3260
2011
Escherichia coli
Pham, N.C.; Moon, J.Y.; Cho, J.H.; Lee, S.J.; Park, J.S.; Kim, D.E.; Park, Y.; Yoon, M.Y.
Characterization of acetohydroxyacid synthase I from Escherichia coli K-12 and identification of its inhibitors
Biosci. Biotechnol. Biochem.
74
2281-2286
2010
Escherichia coli
Belenky, I.; Steinmetz, A.; Vyazmensky, M.; Barak, Z.; Tittmann, K.; Chipman, D.M.
Many of the functional differences between acetohydroxyacid synthase (AHAS) isozyme I and other AHASs are a result of the rapid formation and breakdown of the covalent acetolactate-thiamin diphosphate adduct in AHAS I
FEBS J.
279
1967-1979
2012
Escherichia coli
Gokhale, K.; Tilak, B.
Mechanisms of bacterial acetohydroxyacid synthase (AHAS) and specific inhibitors of Mycobacterium tuberculosis AHAS as potential drug candidates against tuberculosis
Curr. Drug Targets
16
689-699
2015
Saccharomyces cerevisiae, Mycobacterium tuberculosis, Mycobacterium tuberculosis (P9WG41 and P9WKJ3), Pseudomonas aeruginosa, Salmonella enterica subsp. enterica serovar Typhimurium, Escherichia coli (P00892 and P0ADG1), Escherichia coli (P00893 and P00894), Escherichia coli (P08142 and P0ADF8), Mycobacterium tuberculosis H37Rv (P9WG41 and P9WKJ3)
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