2.3.3.13: 2-isopropylmalate synthase
This is an abbreviated version!
For detailed information about 2-isopropylmalate synthase, go to the full flat file.
Word Map on EC 2.3.3.13
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2.3.3.13
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l-leucine
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4.1.3.12
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alpha-ketoisovalerate
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homocitrate
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beta-isopropylmalate
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citramalate
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methylthioalkylmalate
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alpha-ketobutyrate
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alpha-ketoisocaproate
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feedback-resistant
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acetohydroxyacid
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acetohydroxy
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accoa
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medicine
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agriculture
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drug development
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food industry
- 2.3.3.13
- l-leucine
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4.1.3.12
- alpha-ketoisovalerate
- homocitrate
- beta-isopropylmalate
- citramalate
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methylthioalkylmalate
- alpha-ketobutyrate
- alpha-ketoisocaproate
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feedback-resistant
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acetohydroxyacid
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acetohydroxy
- accoa
- medicine
- agriculture
- drug development
- food industry
Reaction
Synonyms
2-isopropylmalate synthase 1, chloroplastic, 2-isopropylmalate synthase 2, chloroplastic, 3-hydroxy-4-methyl-3-carboxy-pentanoate 2-oxo-3-methyl-butanoate lyase (CoA-acetylating), 3-hydroxy-4-methyl-3-carboxyvalerate 2-oxo-3-methyl-butyrate lyase (CoA-acetylating), alpha-IPM synthase, Alpha-IPM synthetase, alpha-IPMS, alpha-IPMS-14CR, alpha-IPMS-2CR, Alpha-isopropylmalate synthase, alpha-isopropylmalate synthase I, alpha-isopropylmalate synthase II, alpha-isopropylmalate synthetase, alpha-isopropylmalic synthetase, BatIMS, EC 4.1.3.12, IPM synthase, IPM-synthase, IPMS, IPMS1, IPMS2, IPMS3, isopropylmalate synthase, isopropylmalate synthase 1, isopropylmalate synthetase, LEU4, LEU9, leuA, Mj1195, MtalphaIPMS, MtIPMS, NmeIPMS, Os11g04670, Os12g04440, OsIPMS1, OsIPMS2, ROL17, synthase, 2-isopropylmalate, synthase, alpha-isopropylmalate, TT_C0849
ECTree
2.3.3.13 2-isopropylmalate synthaseAdvanced search results
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results (Inhibitors
Inhibitors on EC 2.3.3.13 - 2-isopropylmalate synthase
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INHIBITOR 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
IMAGE
isoleucine
inhibited by leucine and isoleucine. Leucine is a more effective inhibitor
isopropylmalate
-
competitive against both 2-oxo-3-methylbutanoate and acetyl-CoA
Leu
inhibition of both enzymes reaches a maximum of 30% to 35% around 1 mM Leu; inhibition of both enzymes reaches a maximum of 30% to 35% around 1 mM Leu
Cd2+
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the ion interacts directly with the catalytic domain of the enzyme and induce unfolding/denaturation of the domain
CoA
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in presence of Zn2+, protection by high concentrations of ATP, and to a much lesser extent, ADP, by a high adenylate charge, by chelators, and by 3'-dephospho-CoA
CoA
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two distinct CoA sites on each enzyme subunit: the first site interacts with CoA an desulfo-CoA, the second site is absolutely specific for CoA. Binding of CoA to this site occurs only when Zn2+ is present, is independent of the specific activity of the enzyme and does not eliminate CoA binding at the product site; Zn2+-dependent reversible inactivation
EDTA
10 mM, complete loss of activity; 10 mM, complete loss of activity
EDTA
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time-dependent inactivation is not reversible by intensive dialysis
EDTA
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Mn2+ plus dithiothreitol restores activity, 2-oxo-3-methylbutanoate prevents inactivation
EDTA
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dialysis at an initial concentration of 50 mM reduces the zinc content by more than 80%, complete loss of activity, restored by addition of Zn2+, Mn2+, Fe2+, Co2+, or Cd2+
L-leucine
partially inhibited by L-leucine in a V-type manner
L-leucine
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noncompetitive inhibitor versus 2-oxo-3-methylbutanoate
L-leucine
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the enzyme retains approximately 10% activity in the presence of saturating concentrations of L-leucine
L-leucine
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isoform Leu4, but not Leu9, is feedback inhibited by L-leucine
leucine
1 mM, 30-35% inhibition, both isoforms IPMS1 and IPMS2
leucine
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competitive with respect to 2-oxo-3-methylbutanoate, non-competitive with respect to acetyl-CoA
leucine
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at low concentrations of Leu the inhibition mechanism is of the competitive type with respect to substrate acetyl-CoA and of the non-competitive type with respect to 2-oxo-3-methylbutanoate; L-Leu
leucine
Hydrogenomonas sp.
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non-competitive, sensitivity is maximal at pH 7.2 and negligible at pH 8.4
leucine
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both Fe2+ and Co2+ lower the inhibition by Leu; D-Leu, weak; mixed-type inhibition, strongly pH-dependent, Leu concentration necessary for half-maximal inhibition increases about 10fold as the pH increases from 7.5 to 8.5
leucine
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pH: 7.2, complete inhibition, pH: 8.0, 70% inhibition, pH: 8.8, 15% inhibition
leucine
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the enzyme from the mutant strain CV241 is insensitive to feedback inhibition by Leu due to a mutation at the extreme operator-distal end of leuA
leucine
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end-product inhibition, non-competitive with respect to 2-oxo-3-methylbutanoate and competitive with respect to acetyl-CoA, more sensitive at pH 6.5 than pH 8.5
leucine
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mechanism of feedback inhibition by Leu, binding of Leu to wild-type and feedback-resistant enzyme and its structural consequences
leucine
inhibited by leucine and isoleucine. Leucine is a more effective inhibitor
Mg2+
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hydrolysis activity of the wild type enzyme is inhibited by increasing concentrations of Mg2+ with IC50 values in the low millimolar range
Zn2+
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the ion interacts directly with the catalytic domain of the enzyme and induce unfolding/denaturation of the domain
additional information
in silico identification of putative inhibitors against alpha-isopropylmalate synthetase exploring three chemical databases i.e. NCI, DrugBank and ChEMBL is reported through structure based drug design and filtering of ligands based on the pharmacophore feature of the actives. The generation of focused library can help in reducing computational time for virtual screening. Altogether, from DrugBank and ChEMBL, eight potential inhibitors have been found which have relatively better binding affinity than known active compounds, out of which CHEMBL404748 and CHEMBL1159999 are suggested to be the most potent against alpha-isopropylmalate synthetase
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additional information
isoform IPMS3 is not subject to L-leucine feedback inhibition; isoform IPMS3 is not subject to L-leucine feedback inhibition
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additional information
isoform IPMS3 is not subject to L-leucine feedback inhibition; isoform IPMS3 is not subject to L-leucine feedback inhibition
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additional information
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isoform IPMS3 is not subject to L-leucine feedback inhibition; isoform IPMS3 is not subject to L-leucine feedback inhibition
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