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Literature summary extracted from

  • Huisman, F.H.; Squire, C.J.; Parker, E.J.
    Amino-acid substitutions at the domain interface affect substrate and allosteric inhibitor binding in alpha-isopropylmalate synthase from Mycobacterium tuberculosis (2013), Biochem. Biophys. Res. Commun., 433, 249-254.
    View publication on PubMed

Protein Variants

EC Number Protein Variants Comment Organism
2.3.3.13 D444A the mutant shows increased catalytic efficiency compared to the wild type enzyme Mycobacterium tuberculosis
2.3.3.13 D444R the mutant shows increased catalytic efficiency compared to the wild type enzyme Mycobacterium tuberculosis
2.3.3.13 D444Y the mutant shows decreased catalytic efficiency compared to the wild type enzyme Mycobacterium tuberculosis
2.3.3.13 R97A the mutant shows increased catalytic efficiency compared to the wild type enzyme Mycobacterium tuberculosis

Inhibitors

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

KM Value [mM]

EC Number KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
2.3.3.13 0.005
-
 3-methyl-2-oxobutanoate mutant enzyme D444A, at pH 7.5 and 25°C Mycobacterium tuberculosis
2.3.3.13 0.008
-
 3-methyl-2-oxobutanoate mutant enzyme R97A, at pH 7.5 and 25°C Mycobacterium tuberculosis
2.3.3.13 0.009
-
 3-methyl-2-oxobutanoate mutant enzyme D444R, at pH 7.5 and 25°C Mycobacterium tuberculosis
2.3.3.13 0.015
-
 3-methyl-2-oxobutanoate wild type enzyme, at pH 7.5 and 25°C Mycobacterium tuberculosis
2.3.3.13 0.016
-
 3-methyl-2-oxobutanoate mutant enzyme D444Y, at pH 7.5 and 25°C Mycobacterium tuberculosis
2.3.3.13 0.027
-
 acetyl-CoA mutant enzyme D444R, at pH 7.5 and 25°C Mycobacterium tuberculosis
2.3.3.13 0.042
-
 acetyl-CoA mutant enzyme D444A, at pH 7.5 and 25°C Mycobacterium tuberculosis
2.3.3.13 0.042
-
 acetyl-CoA mutant enzyme D444Y, at pH 7.5 and 25°C Mycobacterium tuberculosis
2.3.3.13 0.14
-
 acetyl-CoA wild type enzyme, at pH 7.5 and 25°C Mycobacterium tuberculosis
2.3.3.13 0.21
-
 acetyl-CoA mutant enzyme R97A, at pH 7.5 and 25°C Mycobacterium tuberculosis

Metals/Ions

EC Number Metals/Ions Comment Organism Structure
2.3.3.13 Mg2+ activates 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
-
 ?

Organism

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

Purification (Commentary)

EC Number Purification (Comment) Organism
2.3.3.13 TALON affinity resin column chromatography 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
-
 ?

Subunits

EC Number Subunits Comment Organism
2.3.3.13 homodimer
-
 Mycobacterium tuberculosis

Synonyms

EC Number Synonyms Comment Organism
2.3.3.13 alpha-IPMS
-
 Mycobacterium tuberculosis
2.3.3.13 Alpha-isopropylmalate synthase
-
 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 3.1
-
 3-methyl-2-oxobutanoate mutant enzyme D444A, at pH 7.5 and 25°C Mycobacterium tuberculosis
2.3.3.13 3.4
-
 3-methyl-2-oxobutanoate mutant enzyme D444Y, at pH 7.5 and 25°C Mycobacterium tuberculosis
2.3.3.13 3.7
-
 3-methyl-2-oxobutanoate wild type enzyme, at pH 7.5 and 25°C Mycobacterium tuberculosis
2.3.3.13 5.7
-
 3-methyl-2-oxobutanoate mutant enzyme D444R, at pH 7.5 and 25°C Mycobacterium tuberculosis
2.3.3.13 7
-
 3-methyl-2-oxobutanoate mutant enzyme R97A, at pH 7.5 and 25°C Mycobacterium tuberculosis

kcat/KM [mM/s]

EC Number kcat/KM Value [1/mMs-1] kcat/KM Value Maximum [1/mMs-1] Substrate Comment Organism Structure
2.3.3.13 27
-
 acetyl-CoA wild type enzyme, at pH 7.5 and 25°C Mycobacterium tuberculosis
2.3.3.13 33
-
 acetyl-CoA mutant enzyme R97A, at pH 7.5 and 25°C Mycobacterium tuberculosis
2.3.3.13 70
-
 acetyl-CoA mutant enzyme D444A, at pH 7.5 and 25°C Mycobacterium tuberculosis
2.3.3.13 80
-
 acetyl-CoA mutant enzyme D444Y, at pH 7.5 and 25°C Mycobacterium tuberculosis
2.3.3.13 210
-
 acetyl-CoA mutant enzyme D444R, at pH 7.5 and 25°C Mycobacterium tuberculosis
2.3.3.13 210
-
 3-methyl-2-oxobutanoate mutant enzyme D444Y, at pH 7.5 and 25°C Mycobacterium tuberculosis
2.3.3.13 250
-
 3-methyl-2-oxobutanoate wild type enzyme, at pH 7.5 and 25°C Mycobacterium tuberculosis
2.3.3.13 600
-
 3-methyl-2-oxobutanoate mutant enzyme D444A, at pH 7.5 and 25°C Mycobacterium tuberculosis
2.3.3.13 630
-
 3-methyl-2-oxobutanoate mutant enzyme D444R, at pH 7.5 and 25°C Mycobacterium tuberculosis
2.3.3.13 900
-
 3-methyl-2-oxobutanoate mutant enzyme R97A, at pH 7.5 and 25°C Mycobacterium tuberculosis