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Literature summary extracted from

  • Schlachter, C.R.; Klapper, V.; Radford, T.; Chruszcz, M.
    Comparative studies of Aspergillus fumigatus 2-methylcitrate synthase and human citrate synthase (2019), Biol. Chem., 400, 1567-1581 .
    View publication on PubMed

Application

EC Number Application Comment Organism
2.3.3.5 drug development the fungi-specific 2-methylcitrate cycle is responsible for detoxifying propionyl-CoA, a toxic metabolite produced as the fungus breaks down proteins and amino acids. The enzyme responsible for this detoxification is 2-methylcitrate synthase (mcsA) and is a potential candidate for the design of new anti-fungals Aspergillus fumigatus

Cloned(Commentary)

EC Number Cloned (Comment) Organism
2.3.3.1 expression in Escherichia coli Homo sapiens
2.3.3.5 expression in Escherichia coli Aspergillus fumigatus

Crystallization (Commentary)

EC Number Crystallization (Comment) Organism
2.3.3.1 comparison of crystal structures of human enzyme and Aspergillus fumigatus 2-methylcitrate synthase, EC 2.3.3.5, both wild-type and mutants A348G and G352A, respectively Homo sapiens
2.3.3.1 crystallization is performed at room temperature using the sitting-drop vapor diffusion method and MRC 2-drop 96-well crystallization plates Homo sapiens
2.3.3.5 crystallization is performed at room temperature using the sitting-drop vapor diffusion method and MRC 2-drop 96-well crystallization plates Aspergillus fumigatus

Protein Variants

EC Number Protein Variants Comment Organism
2.3.3.1 A348G mutation to the corresponding residue of Aspergillus fumigatus 2-methylcitrate synthase. Active site residues Arg448 (chain B) and His347 (chain A) are not in their normal positions for oxaloacetate binding Homo sapiens
2.3.3.1 G386A insoluble enzyme variant Homo sapiens
2.3.3.5 AW81Y no measurable activity Aspergillus fumigatus
2.3.3.5 G352A mutation does not appear to have an impact on positioning of active site residues Aspergillus fumigatus
2.3.3.5 G419A no measurable activity Aspergillus fumigatus

Inhibitors

EC Number Inhibitors Comment Organism Structure
2.3.3.1 3,3-thiodipropionate substrate acetyl-CoA, competitive; substrate oxaloacetate, competitive Homo sapiens
2.3.3.1 3,3-thiodipropionic acid competitive inhibition versus acetyl-CoA and versus oxaloacetate Homo sapiens
2.3.3.1 3-phosphonopropionic acid competitive inhibition versus acetyl-CoA and versus oxaloacetate Homo sapiens
2.3.3.1 3-phosphopropionate substrate acetyl-CoA, competitive; substrate oxaloacetate, competitive Homo sapiens
2.3.3.1 Dihydroxyfumarate substrate acetyl-CoA, competitive; substrate oxaloacetate, competitive Homo sapiens
2.3.3.1 dihydroxyfumaric acid competitive inhibition versus acetyl-CoA and versus oxaloacetate Homo sapiens
2.3.3.1 DL-malate substrate acetyl-CoA, mixed type inhibition; substrate oxaloacetate, mixed type inhibition Homo sapiens
2.3.3.1 DL-malic acid mixed type inhibition versus acetyl-CoA and versus oxaloacetate Homo sapiens
2.3.3.1 Maleate substrate acetyl-CoA, mixed type inhibition; substrate oxaloacetate, mixed type inhibition Homo sapiens
2.3.3.1 Maleic acid mixed type inhibition versus acetyl-CoA and versus oxaloacetate Homo sapiens
2.3.3.1 potassium hydroxycitrate competitive inhibition versus acetyl-CoA and versus oxaloacetate; substrate acetyl-CoA, competitive; substrate oxaloacetate, competitive Homo sapiens
2.3.3.1 propionate competitive inhibition versus oxaloacetate, mixed type inhibition versus acetyl-CoA; substrate acetyl-CoA, competitive; substrate oxaloacetate, competitive Homo sapiens
2.3.3.5 3,3-thiodipropionic acid competitive inhibition versus propionyl-CoA and versus oxaloacetate Aspergillus fumigatus
2.3.3.5 3-phosphonopropionic acid competitive inhibition versus propionyl-CoA, mixed type inhibition versus oxaloacetate Aspergillus fumigatus
2.3.3.5 dihydroxyfumaric acid competitive inhibition versus propionyl-CoA, mixed type inhibition versus oxaloacetate Aspergillus fumigatus
2.3.3.5 DL-malic acid noncompetitive inhibition versus propionyl-CoA and versus oxaloacetate Aspergillus fumigatus
2.3.3.5 Maleic acid noncompetitive inhibition versus propionyl-CoA, competitive inhibition versus oxaloacetate Aspergillus fumigatus
2.3.3.5 potassium hydroxycitrate competitive inhibition versus propionyl-CoA, noncompetitive inhibition versus oxaloacetate Aspergillus fumigatus
2.3.3.5 propionate competitive inhibition versus propionyl-CoA, noncompetitive inhibition versus oxaloacetate Aspergillus fumigatus

KM Value [mM]

EC Number KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
2.3.3.1 0.0036
-
 oxaloacetate wild-type, pH 8.0, temperature not specified in the publication Homo sapiens
2.3.3.1 0.0036
-
 oxaloacetate pH 8.0, temperature not specified in the publication, wild-type enzyme Homo sapiens
2.3.3.1 0.0057
-
 oxaloacetate mutant A348G, pH 8.0, temperature not specified in the publication Homo sapiens
2.3.3.1 0.0057
-
 oxaloacetate pH 8.0, temperature not specified in the publication, mutant enzyme G348G Homo sapiens
2.3.3.1 0.0077
-
 acetyl-CoA wild-type, pH 8.0, temperature not specified in the publication Homo sapiens
2.3.3.1 0.0077
-
 acetyl-CoA pH 8.0, temperature not specified in the publication, wild-type enzyme Homo sapiens
2.3.3.1 0.0104
-
 acetyl-CoA mutant A348G, pH 8.0, temperature not specified in the publication Homo sapiens
2.3.3.1 0.0104
-
 acetyl-CoA pH 8.0, temperature not specified in the publication, mutant enzyme G348G Homo sapiens
2.3.3.5 0.0035
-
 oxaloacetate pH 8.0, temperature not specified in the publication, mutant enzyme G352A Aspergillus fumigatus
2.3.3.5 0.0036
-
 acetyl-CoA pH 8.0, temperature not specified in the publication, mutant enzyme G352A Aspergillus fumigatus
2.3.3.5 0.0039
-
 propanoyl-CoA pH 8.0, temperature not specified in the publication, mutant enzyme G352A Aspergillus fumigatus
2.3.3.5 0.0047
-
 propanoyl-CoA pH 8.0, temperature not specified in the publication, wild-type enzyme Aspergillus fumigatus
2.3.3.5 0.0049
-
 oxaloacetate pH 8.0, temperature not specified in the publication, wild-type enzyme Aspergillus fumigatus
2.3.3.5 0.005
-
 acetyl-CoA pH 8.0, temperature not specified in the publication, wild-type enzyme Aspergillus fumigatus

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
2.3.3.5 propanoyl-CoA + H2O + oxaloacetate Aspergillus fumigatus the fungi-specific 2-methylcitrate cycle is responsible for detoxifying propionyl-CoA, a toxic metabolite produced as the fungus breaks down proteins and amino acids. The enzyme responsible for this detoxification is 2-methylcitrate synthase (mcsA) and is a potential candidate for the design of new anti-fungals (2S,3S)-2-hydroxybutane-1,2,3-tricarboxylate + CoA
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
2.3.3.1 Homo sapiens O75390
-
-
2.3.3.5 Aspergillus fumigatus Q50I20 i.e. Aspergillus fumigatus
-

Purification (Commentary)

EC Number Purification (Comment) Organism
2.3.3.1
-
 Homo sapiens
2.3.3.5
-
 Aspergillus fumigatus

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
2.3.3.1 acetyl-CoA + H2O + oxaloacetate
-
 Homo sapiens citrate + CoA
-
 ?
2.3.3.5 acetyl-CoA + H2O + oxaloacetate
-
 Aspergillus fumigatus citrate + CoA
-
 ?
2.3.3.5 propanoyl-CoA + H2O + oxaloacetate
-
 Aspergillus fumigatus (2S,3S)-2-hydroxybutane-1,2,3-tricarboxylate + CoA
-
 ?
2.3.3.5 propanoyl-CoA + H2O + oxaloacetate the fungi-specific 2-methylcitrate cycle is responsible for detoxifying propionyl-CoA, a toxic metabolite produced as the fungus breaks down proteins and amino acids. The enzyme responsible for this detoxification is 2-methylcitrate synthase (mcsA) and is a potential candidate for the design of new anti-fungals Aspergillus fumigatus (2S,3S)-2-hydroxybutane-1,2,3-tricarboxylate + CoA
-
 ?

Synonyms

EC Number Synonyms Comment Organism
2.3.3.1 HCS
-
 Homo sapiens
2.3.3.5 mcsA
-
 Aspergillus fumigatus

Turnover Number [1/s]

EC Number Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
2.3.3.1 111
-
 oxaloacetate mutant A348G, pH 8.0, temperature not specified in the publication Homo sapiens
2.3.3.1 111
-
 oxaloacetate pH 8.0, temperature not specified in the publication, mutant enzyme G348G Homo sapiens
2.3.3.1 117
-
 acetyl-CoA mutant A348G, pH 8.0, temperature not specified in the publication Homo sapiens
2.3.3.1 117
-
 acetyl-CoA pH 8.0, temperature not specified in the publication, mutant enzyme G348G Homo sapiens
2.3.3.1 208
-
 oxaloacetate wild-type, pH 8.0, temperature not specified in the publication Homo sapiens
2.3.3.1 208
-
 oxaloacetate pH 8.0, temperature not specified in the publication, wild-type enzyme Homo sapiens
2.3.3.1 260
-
 acetyl-CoA wild-type, pH 8.0, temperature not specified in the publication Homo sapiens
2.3.3.1 260
-
 acetyl-CoA pH 8.0, temperature not specified in the publication, wild-type enzyme Homo sapiens
2.3.3.5 10.4
-
 acetyl-CoA pH 8.0, temperature not specified in the publication, mutant enzyme G352A Aspergillus fumigatus
2.3.3.5 11.2
-
 oxaloacetate pH 8.0, temperature not specified in the publication, mutant enzyme G352A Aspergillus fumigatus
2.3.3.5 12.2
-
 propanoyl-CoA pH 8.0, temperature not specified in the publication, mutant enzyme G352A Aspergillus fumigatus
2.3.3.5 29.2
-
 oxaloacetate pH 8.0, temperature not specified in the publication, wild-type enzyme Aspergillus fumigatus
2.3.3.5 30.1
-
 propanoyl-CoA pH 8.0, temperature not specified in the publication, wild-type enzyme Aspergillus fumigatus
2.3.3.5 32.7
-
 acetyl-CoA pH 8.0, temperature not specified in the publication, wild-type enzyme Aspergillus fumigatus

pH Optimum

EC Number pH Optimum Minimum pH Optimum Maximum Comment Organism
2.3.3.1 8
-
 assay at Homo sapiens
2.3.3.5 8
-
 assay at Aspergillus fumigatus

Ki Value [mM]

EC Number Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
2.3.3.1 6.5
-
 DL-malic acid pH 8.0, temperature not specified in the publication, substrate: propionyl-CoA Homo sapiens
2.3.3.1 6.5
-
 DL-malate substrate acetyl-CoA, pH 8.0, temperature not specified in the publication Homo sapiens
2.3.3.1 8
-
 potassium hydroxycitrate pH 8.0, temperature not specified in the publication, substrate: oxaloacetate Homo sapiens
2.3.3.1 8
-
 potassium hydroxycitrate substrate oxaloacetate, pH 8.0, temperature not specified in the publication Homo sapiens
2.3.3.1 14.2
-
 DL-malic acid pH 8.0, temperature not specified in the publication, substrate: oxaloacetate Homo sapiens
2.3.3.1 14.2
-
 DL-malate substrate oxaloacetate, pH 8.0, temperature not specified in the publication Homo sapiens
2.3.3.1 14.6
-
 potassium hydroxycitrate pH 8.0, temperature not specified in the publication, substrate: propionyl-CoA Homo sapiens
2.3.3.1 14.6
-
 potassium hydroxycitrate substrate acetyl-CoA, pH 8.0, temperature not specified in the publication Homo sapiens
2.3.3.1 17.5
-
 Maleic acid pH 8.0, temperature not specified in the publication, substrate: propionyl-CoA Homo sapiens
2.3.3.1 17.5
-
 Maleate substrate acetyl-CoA, pH 8.0, temperature not specified in the publication Homo sapiens
2.3.3.1 20
-
 Maleic acid pH 8.0, temperature not specified in the publication, substrate: oxaloacetate Homo sapiens
2.3.3.1 20
-
 Maleate substrate oxaloacetate, pH 8.0, temperature not specified in the publication Homo sapiens
2.3.3.1 21.2
-
 3-phosphonopropionic acid pH 8.0, temperature not specified in the publication, substrate: propionyl-CoA Homo sapiens
2.3.3.1 21.2
-
 3-phosphopropionate substrate acetyl-CoA, pH 8.0, temperature not specified in the publication Homo sapiens
2.3.3.1 22.3
-
 3,3-thiodipropionic acid pH 8.0, temperature not specified in the publication, substrate: propionyl-CoA Homo sapiens
2.3.3.1 22.3
-
 3,3-thiodipropionate substrate acetyl-CoA, pH 8.0, temperature not specified in the publication Homo sapiens
2.3.3.1 24.2
-
 3,3-thiodipropionic acid pH 8.0, temperature not specified in the publication, substrate: oxaloacetate Homo sapiens
2.3.3.1 24.2
-
 3,3-thiodipropionate substrate oxaloacetate, pH 8.0, temperature not specified in the publication Homo sapiens
2.3.3.1 25.1
-
 propionate pH 8.0, temperature not specified in the publication, substrate: propionyl-CoA Homo sapiens
2.3.3.1 25.1
-
 propionate substrate acetyl-CoA, pH 8.0, temperature not specified in the publication Homo sapiens
2.3.3.1 28.1
-
 propionate pH 8.0, temperature not specified in the publication, substrate: oxaloacetate Homo sapiens
2.3.3.1 28.1
-
 propionate substrate oxaloacetate, pH 8.0, temperature not specified in the publication Homo sapiens
2.3.3.1 71.7
-
 3-phosphonopropionic acid pH 8.0, temperature not specified in the publication, substrate: oxaloacetate Homo sapiens
2.3.3.1 71.7
-
 3-phosphopropionate substrate oxaloacetate, pH 8.0, temperature not specified in the publication Homo sapiens
2.3.3.1 73
-
 dihydroxyfumaric acid pH 8.0, temperature not specified in the publication, substrate: propionyl-CoA Homo sapiens
2.3.3.1 73
-
 Dihydroxyfumarate substrate acetyl-CoA, pH 8.0, temperature not specified in the publication Homo sapiens
2.3.3.1 90.5
-
 dihydroxyfumaric acid pH 8.0, temperature not specified in the publication, substrate: oxaloacetate Homo sapiens
2.3.3.1 90.5
-
 Dihydroxyfumarate substrate oxaloacetate, pH 8.0, temperature not specified in the publication Homo sapiens
2.3.3.5 6.9
-
 potassium hydroxycitrate pH 8.0, temperature not specified in the publication, substrate: propionyl-CoA Aspergillus fumigatus
2.3.3.5 16.6
-
 potassium hydroxycitrate pH 8.0, temperature not specified in the publication, substrate: oxaloacetate Aspergillus fumigatus
2.3.3.5 17.1
-
 dihydroxyfumaric acid pH 8.0, temperature not specified in the publication, substrate: propionyl-CoA Aspergillus fumigatus
2.3.3.5 18
-
 propionate pH 8.0, temperature not specified in the publication, substrate: propionyl-CoA Aspergillus fumigatus
2.3.3.5 23.1
-
 3-phosphonopropionic acid pH 8.0, temperature not specified in the publication, substrate: propionyl-CoA Aspergillus fumigatus
2.3.3.5 23.6
-
 dihydroxyfumaric acid pH 8.0, temperature not specified in the publication, substrate: oxaloacetate Aspergillus fumigatus
2.3.3.5 30.9
-
 Maleic acid pH 8.0, temperature not specified in the publication, substrate: oxaloacetate Aspergillus fumigatus
2.3.3.5 34.4
-
 3-phosphonopropionic acid pH 8.0, temperature not specified in the publication, substrate: oxaloacetate Aspergillus fumigatus
2.3.3.5 45.1
-
 3,3-thiodipropionic acid pH 8.0, temperature not specified in the publication, substrate: propionyl-CoA Aspergillus fumigatus
2.3.3.5 52.1
-
 3,3-thiodipropionic acid pH 8.0, temperature not specified in the publication, substrate: oxaloacetate Aspergillus fumigatus
2.3.3.5 62.1
-
 DL-malic acid pH 8.0, temperature not specified in the publication, substrate: propionyl-CoA Aspergillus fumigatus
2.3.3.5 67.5
-
 DL-malic acid pH 8.0, temperature not specified in the publication, substrate: oxaloacetate Aspergillus fumigatus
2.3.3.5 74.6
-
 propionate pH 8.0, temperature not specified in the publication, substrate: oxaloacetate Aspergillus fumigatus
2.3.3.5 97.3
-
 Maleic acid pH 8.0, temperature not specified in the publication, substrate: propionyl-CoA Aspergillus fumigatus

General Information

EC Number General Information Comment Organism
2.3.3.5 metabolism the fungi-specific 2-methylcitrate cycle is responsible for detoxifying propionyl-CoA, a toxic metabolite produced as the fungus breaks down proteins and amino acids. The enzyme responsible for this detoxification is 2-methylcitrate synthase (mcsA) and is a potential candidate for the design of new anti-fungals Aspergillus fumigatus

kcat/KM [mM/s]

EC Number kcat/KM Value [1/mMs-1] kcat/KM Value Maximum [1/mMs-1] Substrate Comment Organism Structure
2.3.3.1 11000
-
 acetyl-CoA mutant A348G, pH 8.0, temperature not specified in the publication Homo sapiens
2.3.3.1 11000
-
 acetyl-CoA pH 8.0, temperature not specified in the publication, mutant enzyme G348G Homo sapiens
2.3.3.1 19000
-
 oxaloacetate mutant A348G, pH 8.0, temperature not specified in the publication Homo sapiens
2.3.3.1 19000
-
 oxaloacetate pH 8.0, temperature not specified in the publication, mutant enzyme G348G Homo sapiens
2.3.3.1 34000
-
 acetyl-CoA wild-type, pH 8.0, temperature not specified in the publication Homo sapiens
2.3.3.1 34000
-
 acetyl-CoA pH 8.0, temperature not specified in the publication, wild-type enzyme Homo sapiens
2.3.3.1 59000
-
 oxaloacetate wild-type, pH 8.0, temperature not specified in the publication Homo sapiens
2.3.3.1 59000
-
 oxaloacetate pH 8.0, temperature not specified in the publication, wild-type enzyme Homo sapiens
2.3.3.5 2900
-
 acetyl-CoA pH 8.0, temperature not specified in the publication, mutant enzyme G352A Aspergillus fumigatus
2.3.3.5 3200
-
 oxaloacetate pH 8.0, temperature not specified in the publication, mutant enzyme G352A Aspergillus fumigatus
2.3.3.5 3200
-
 propanoyl-CoA pH 8.0, temperature not specified in the publication, mutant enzyme G352A Aspergillus fumigatus
2.3.3.5 6000
-
 oxaloacetate pH 8.0, temperature not specified in the publication, wild-type enzyme Aspergillus fumigatus
2.3.3.5 6500
-
 propanoyl-CoA pH 8.0, temperature not specified in the publication, wild-type enzyme Aspergillus fumigatus
2.3.3.5 6600
-
 acetyl-CoA pH 8.0, temperature not specified in the publication, wild-type enzyme Aspergillus fumigatus