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Literature summary extracted from

  • de Carvalho, L.P.; Frantom, P.A.; Argyrou, A.; Blanchard, J.S.
    Kinetic evidence for interdomain communication in the allosteric regulation of alpha-isopropylmalate synthase from Mycobacterium tuberculosis (2009), Biochemistry, 48, 1996-2004.
    View publication on PubMedView publication on EuropePMC

Application

EC Number Application Comment Organism
2.3.3.13 medicine alpha-isopropylmalate synthase is a target for the design of new antitubercular therapeutics Mycobacterium tuberculosis

Cloned(Commentary)

EC Number Cloned (Comment) Organism
2.3.3.13 into the vector pET28a for expression in Escherichia coli BL21DE3 pLysS cells Mycobacterium tuberculosis

Protein Variants

EC Number Protein Variants Comment Organism
2.3.3.13 E218A mutant, substitution at phylogenetically conserved active site residue near the interface of the catalytic and linker domains Mycobacterium tuberculosis
2.3.3.13 H379A mutant, substitution at phylogenetically conserved active site residue near the interface of the catalytic and linker domains Mycobacterium tuberculosis
2.3.3.13 Y169F mutant, substitution at phylogenetically conserved active site residue near the interface of the catalytic and linker domains Mycobacterium tuberculosis
2.3.3.13 Y410F mutant, insensitive to L-leucine inhibition Mycobacterium tuberculosis

Inhibitors

EC Number Inhibitors Comment Organism Structure
2.3.3.13 L-leucine feedback inhibition Mycobacterium tuberculosis

KM Value [mM]

EC Number KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
2.3.3.13 0.0005
-
alpha-ketoisovalerate mutant Y410F Mycobacterium tuberculosis
2.3.3.13 0.0011
-
acetyl-CoA mutant Y410F Mycobacterium tuberculosis
2.3.3.13 0.0016
-
alpha-ketoisovalerate mutant E218A, enzyme displays substrate activation, unactivated form Mycobacterium tuberculosis
2.3.3.13 0.0016
-
alpha-ketoisovalerate mutant H379A, enzyme displays substrate activation, unactivated form Mycobacterium tuberculosis
2.3.3.13 0.0023
-
acetyl-CoA mutant H379A Mycobacterium tuberculosis
2.3.3.13 0.0071
-
alpha-ketoisovalerate wild-type Mycobacterium tuberculosis
2.3.3.13 0.0095
-
acetyl-CoA mutant E218A, enzyme displays substrate activation, unactivated form Mycobacterium tuberculosis
2.3.3.13 0.0134
-
alpha-ketoisovalerate mutant Y169F Mycobacterium tuberculosis
2.3.3.13 0.019
-
alpha-ketoisovalerate mutant H379A, enzyme displays substrate activation, activated form Mycobacterium tuberculosis
2.3.3.13 0.024
-
acetyl-CoA wild-type Mycobacterium tuberculosis
2.3.3.13 0.039
-
alpha-ketoisovalerate mutant E218A, enzyme displays substrate activation, activated form Mycobacterium tuberculosis
2.3.3.13 0.04
-
acetyl-CoA mutant Y169F Mycobacterium tuberculosis
2.3.3.13 0.697
-
acetyl-CoA mutant E218A, enzyme displays substrate activation, activated form Mycobacterium tuberculosis

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
2.3.3.13 acetyl-CoA + 3-methyl-2-oxobutanoate + H2O Mycobacterium tuberculosis
-
(2S)-2-isopropylmalate + CoA
-
?
2.3.3.13 acetyl-CoA + 3-methyl-2-oxobutanoate + H2O Mycobacterium tuberculosis H37Rv
-
(2S)-2-isopropylmalate + CoA
-
?

Organism

EC Number Organism UniProt Comment Textmining
2.3.3.13 Mycobacterium tuberculosis P9WQB3
-
-
2.3.3.13 Mycobacterium tuberculosis H37Rv P9WQB3
-
-

Purification (Commentary)

EC Number Purification (Comment) Organism
2.3.3.13 on a nickel-NTA, a Mono-Q and a Phenyl Sepharose column Mycobacterium tuberculosis

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
2.3.3.13 acetyl-CoA + 3-methyl-2-oxobutanoate + H2O
-
Mycobacterium tuberculosis (2S)-2-isopropylmalate + CoA
-
?
2.3.3.13 acetyl-CoA + 3-methyl-2-oxobutanoate + H2O
-
Mycobacterium tuberculosis H37Rv (2S)-2-isopropylmalate + CoA
-
?
2.3.3.13 alpha-ketoisovalerate + H2O + acetyl-CoA
-
Mycobacterium tuberculosis ? + CoA
-
?
2.3.3.13 alpha-ketoisovalerate + H2O + acetyl-CoA
-
Mycobacterium tuberculosis H37Rv ? + CoA
-
?

Synonyms

EC Number Synonyms Comment Organism
2.3.3.13 Alpha-isopropylmalate synthase
-
Mycobacterium tuberculosis
2.3.3.13 MtIPMS
-
Mycobacterium tuberculosis

Temperature Optimum [°C]

EC Number Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
2.3.3.13 25
-
activity assay Mycobacterium tuberculosis

Turnover Number [1/s]

EC Number Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
2.3.3.13 0.022
-
alpha-ketoisovalerate mutant E218A, enzyme displays substrate activation, activated form Mycobacterium tuberculosis
2.3.3.13 0.037
-
alpha-ketoisovalerate mutant E218A, enzyme displays substrate activation, unactivated form Mycobacterium tuberculosis
2.3.3.13 0.058
-
acetyl-CoA mutant E218A, enzyme displays substrate activation, unactivated form Mycobacterium tuberculosis
2.3.3.13 0.075
-
alpha-ketoisovalerate mutant Y410F Mycobacterium tuberculosis
2.3.3.13 0.093
-
acetyl-CoA mutant E218A, enzyme displays substrate activation, activated form Mycobacterium tuberculosis
2.3.3.13 0.093
-
acetyl-CoA mutant Y410F Mycobacterium tuberculosis
2.3.3.13 0.7
-
alpha-ketoisovalerate mutant H379A, enzyme displays substrate activation, unactivated form Mycobacterium tuberculosis
2.3.3.13 1.483
-
alpha-ketoisovalerate mutant H379A, enzyme displays substrate activation, activated form Mycobacterium tuberculosis
2.3.3.13 2.53
-
alpha-ketoisovalerate wild-type Mycobacterium tuberculosis
2.3.3.13 2.55
-
acetyl-CoA mutant H379A Mycobacterium tuberculosis
2.3.3.13 2.717
-
acetyl-CoA wild-type Mycobacterium tuberculosis
2.3.3.13 4.75
-
alpha-ketoisovalerate mutant Y169F Mycobacterium tuberculosis
2.3.3.13 5.667
-
acetyl-CoA mutant Y169F Mycobacterium tuberculosis

pH Optimum

EC Number pH Optimum Minimum pH Optimum Maximum Comment Organism
2.3.3.13 7.5
-
activity assay Mycobacterium tuberculosis

Cofactor

EC Number Cofactor Comment Organism Structure
2.3.3.13 acetyl-CoA
-
Mycobacterium tuberculosis

Ki Value [mM]

EC Number Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
2.3.3.13 0.012
-
L-leucine wild-type Mycobacterium tuberculosis
2.3.3.13 0.018
-
L-leucine mutant Y169F Mycobacterium tuberculosis
2.3.3.13 0.019
-
L-leucine mutant H379A Mycobacterium tuberculosis
2.3.3.13 0.139
-
L-leucine mutant E218A Mycobacterium tuberculosis