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Literature summary extracted from

  • Teuscher, F.; Lowther, J.; Skinner-Adams, T.S.; Spielmann, T.; Dixon, M.W.; Stack, C.M.; Donnelly, S.; Mucha, A.; Kafarski, P.; Vassiliou, S.; Gardiner, D.L.; Dalton, J.P.; Trenholme, K.R.
    The M18 aspartyl aminopeptidase of the human malaria parasite Plasmodium falciparum (2007), J. Biol. Chem., 282, 30817-30826.
    View publication on PubMed

Application

EC Number Application Comment Organism
3.4.11.7 medicine enzyme is a promising target for new anti-malarial drug development Plasmodium falciparum

Cloned(Commentary)

EC Number Cloned (Comment) Organism
3.4.11.7 using codons for optimized gene expression in the yeast Pichia pastoris, for protein expression Sf9 insect cells are infected with PfM18AAP recombinant Baculovirus, furthermore pGEM, pHGFPB and pHcmycB are used Plasmodium falciparum
3.4.11.21 expressed in Sf9 insect cells Plasmodium falciparum

Inhibitors

EC Number Inhibitors Comment Organism Structure
3.4.11.7 (1-aminopropane-1,3-diyl)bis(phosphonic acid)
-
 Plasmodium falciparum
3.4.11.7 (3R)-3-amino-3-phosphonopropanoic acid
-
 Plasmodium falciparum
3.4.11.7 3-amino-3-[hydroxy(phenyl)phosphoryl]propanoic acid
-
 Plasmodium falciparum
3.4.11.7 3-[(1-amino-2-carboxyethyl)(hydroxy)phosphoryl]-2-methylpropanoic acid
-
 Plasmodium falciparum
3.4.11.7 3-[[amino(carboxy)methyl](hydroxy)phosphoryl]-2-methylpropanoic acid
-
 Plasmodium falciparum
3.4.11.7 5-amino-5-phosphonopentanoic acid
-
 Plasmodium falciparum
3.4.11.7 amino(phosphono)acetic acid
-
 Plasmodium falciparum
3.4.11.7 amino[hydroxy(methyl)phosphoryl]acetic acid
-
 Plasmodium falciparum
3.4.11.7 EDTA activity is reduced to 14% after incubating with 10 mM EDTA Plasmodium falciparum
3.4.11.7 o-phenanthroline activity is reduced to 8.3% after incubating with 20 mM o-phenanthroline Plasmodium falciparum
3.4.11.7 Zn2+ Zn2+ abolishes enzyme activity at a concentration of 1 mM Plasmodium falciparum
3.4.11.21 1-amino-1,3-propanediphosphonic acid
-
 Plasmodium falciparum
3.4.11.21 3-amino-3-(P-methylphosphinyl)propionic acid
-
 Plasmodium falciparum
3.4.11.21 3-amino-3-phosphonopropionic acid
-
 Plasmodium falciparum
3.4.11.21 3-amino-3-[P-(2-carboxypropyl)phosphinyl]propionic acid
-
 Plasmodium falciparum
3.4.11.21 4-amino-4-(P-phenylphosphinyl)butyric acid 20% inhibition at 1.83 mM Plasmodium falciparum
3.4.11.21 4-amino-4-phosphonobutyric acid
-
 Plasmodium falciparum
3.4.11.21 4-amino-4-[P-(2-carboxypropyl)phosphinyl]butyric acid
-
 Plasmodium falciparum
3.4.11.21 5-amino-5-phosphonopentanoic acid
-
 Plasmodium falciparum
3.4.11.21 EDTA activity is reduced to 14% after incubating with 10 mM EDTA Plasmodium falciparum
3.4.11.21 o-phenanthroline activity is reduced to 8.3% after incubating with 20 mM o-phenanthroline Plasmodium falciparum
3.4.11.21 Zn2+ Zn2+ abolishes activity at 1 mM Plasmodium falciparum

KM Value [mM]

EC Number KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
3.4.11.7 0.1351
-
 Glu-7-amido-4-methylcoumarin in the absence of cobalt Plasmodium falciparum
3.4.11.7 0.1363
-
 Glu-7-amido-4-methylcoumarin in the presence of 1 mM cobalt Plasmodium falciparum
3.4.11.7 0.3273
-
 Asp-7-amido-4-methylcoumarin in the presence of 1 mM cobalt Plasmodium falciparum
3.4.11.7 0.3848
-
 Asp-7-amido-4-methylcoumarin in the absence of cobalt Plasmodium falciparum
3.4.11.21 0.135
-
 Glu-7-amido-4-methylcoumarin
-
 Plasmodium falciparum
3.4.11.21 0.136
-
 Glu-7-amido-4-methylcoumarin in the presence of 1 mM Co2+ Plasmodium falciparum
3.4.11.21 0.327
-
 Asp-7-amido-4-methylcoumarin in the presence of 1 mM Co2+ Plasmodium falciparum
3.4.11.21 0.385
-
 Asp-7-amido-4-methylcoumarin
-
 Plasmodium falciparum

Localization

EC Number Localization Comment Organism GeneOntology No. Textmining
3.4.11.7 cytosol
-
 Plasmodium falciparum 5829
-
3.4.11.7 vacuole
-
 Plasmodium falciparum 5773
-
3.4.11.21 cytosol
-
 Plasmodium falciparum 5829
-

Metals/Ions

EC Number Metals/Ions Comment Organism Structure
3.4.11.7 Co2+
-
 Plasmodium falciparum
3.4.11.21 Co2+ enhanced activity Plasmodium falciparum
3.4.11.21 additional information activity is not enhanced by Ca2+, Fe2+, Mg2+, Mn2+, and Ni2+ Plasmodium falciparum

Molecular Weight [Da]

EC Number Molecular Weight [Da] Molecular Weight Maximum [Da] Comment Organism
3.4.11.7 65000
-
 determined by reducing SDS-PAGE Plasmodium falciparum
3.4.11.7 560000
-
 octamer, determined by gel filtration HPLC on a Superdex-200 column Plasmodium falciparum
3.4.11.21 65000
-
 8 * 65000, SDS-PAGE Plasmodium falciparum
3.4.11.21 70000
-
 8 * 70000, high performance liquid chromatography Plasmodium falciparum
3.4.11.21 520000
-
 SDS-PAGE Plasmodium falciparum
3.4.11.21 560000
-
 high performance liquid chromatography Plasmodium falciparum

Organism

EC Number Organism UniProt Comment Textmining
3.4.11.7 Plasmodium falciparum Q8I2J3
-
-
3.4.11.21 Plasmodium falciparum
-
-
-

Purification (Commentary)

EC Number Purification (Comment) Organism
3.4.11.7 by affinity chromatography on a Ni-NTA column Plasmodium falciparum
3.4.11.21 Ni-NTA-agarose column chromatography and Superdex-200 gel filtration Plasmodium falciparum

Source Tissue

EC Number Source Tissue Comment Organism Textmining
3.4.11.7 ring stage
-
 Plasmodium falciparum
-

Specific Activity [micromol/min/mg]

EC Number Specific Activity Minimum [µmol/min/mg] Specific Activity Maximum [µmol/min/mg] Comment Organism
3.4.11.7 607
-
 Glu-7-amido-4-methylcoumarin Plasmodium falciparum
3.4.11.7 662.5
-
 Asp-7-amido-4-methylcoumarin Plasmodium falciparum

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
3.4.11.7 Asp-7-amido-4-methylcoumarin + H2O assay for measuring aspartyl aminopeptidase activity Plasmodium falciparum Asp + 7-amino-4-methylcoumarin
-
 ?
3.4.11.7 Glu-7-amido-4-methylcoumarin + H2O assay for measuring aspartyl aminopeptidase activity Plasmodium falciparum Glu + 7-amino-4-methylcoumarin
-
 ?
3.4.11.7 Leu-7-amido-4-methylcoumarin + H2O assay for measuring aspartyl aminopeptidase activity Plasmodium falciparum Leu + 7-amino-4-methylcoumarin
-
 ?
3.4.11.21 Asp-7-amido-4-methylcoumarin + H2O
-
 Plasmodium falciparum Asp + 7-amino-4-methylcoumarin
-
 ?
3.4.11.21 Glu-7-amido-4-methylcoumarin + H2O
-
 Plasmodium falciparum Glu + 7-amino-4-methylcoumarin
-
 ?
3.4.11.21 additional information no hydrolysis is observed against Leu-7-amido-4-methylcoumarin, Phe-7-amido-4-methylcoumarin, Ala-7-amido-4-methylcoumarin, Pro-7-amido-4-methylcoumarin, Gly-7-amido-4-methylcoumarin, Val-7-amido-4-methylcoumarin, Arg-7-amido-4-methylcoumarin, and Ile-7-amido-4-methylcoumarin Plasmodium falciparum ?
-
 ?

Subunits

EC Number Subunits Comment Organism
3.4.11.7 octamer
-
 Plasmodium falciparum
3.4.11.21 homooctamer 8 * 65000, SDS-PAGE Plasmodium falciparum
3.4.11.21 homooctamer 8 * 70000, high performance liquid chromatography Plasmodium falciparum

Synonyms

EC Number Synonyms Comment Organism
3.4.11.7 Aminopeptidase
-
 Plasmodium falciparum
3.4.11.7 aspartyl aminopeptidase
-
 Plasmodium falciparum
3.4.11.7 M18 aspartyl aminopeptidase
-
 Plasmodium falciparum
3.4.11.21 M18 aspartyl aminopeptidase
-
 Plasmodium falciparum
3.4.11.21 M18AAP
-
 Plasmodium falciparum

Temperature Optimum [°C]

EC Number Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
3.4.11.7 37
-
 activity assay Plasmodium falciparum

Temperature Stability [°C]

EC Number Temperature Stability Minimum [°C] Temperature Stability Maximum [°C] Comment Organism
3.4.11.21 37
-
 stable when stored for 1 h at 37°C over the pH range 6 to 11 Plasmodium falciparum

Turnover Number [1/s]

EC Number Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
3.4.11.7 0.011
-
 Glu-7-amido-4-methylcoumarin in the absence of cobalt Plasmodium falciparum
3.4.11.7 0.05
-
 Asp-7-amido-4-methylcoumarin in the absence of cobalt Plasmodium falciparum
3.4.11.7 0.33
-
 Glu-7-amido-4-methylcoumarin in the presence of 1 mM cobalt Plasmodium falciparum
3.4.11.7 0.354
-
 Asp-7-amido-4-methylcoumarin in the presence of 1 mM cobalt Plasmodium falciparum
3.4.11.21 0.011
-
 Glu-7-amido-4-methylcoumarin at pH 7.5, in the absesence of Co2+ Plasmodium falciparum
3.4.11.21 0.05
-
 Asp-7-amido-4-methylcoumarin at pH 7.5, in the absence of Co2+ Plasmodium falciparum
3.4.11.21 0.33
-
 Glu-7-amido-4-methylcoumarin at pH 7.5, in the presence of 1 mM Co2+ Plasmodium falciparum
3.4.11.21 0.354
-
 Asp-7-amido-4-methylcoumarin at pH 7.5, in the presence of 1 mM Co2+ Plasmodium falciparum

pH Optimum

EC Number pH Optimum Minimum pH Optimum Maximum Comment Organism
3.4.11.7 7.5
-
 activity assay Plasmodium falciparum
3.4.11.21 7.5
-
-
 Plasmodium falciparum

pH Range

EC Number pH Minimum pH Maximum Comment Organism
3.4.11.7 6 9
-
 Plasmodium falciparum
3.4.11.21 6 9
-
 Plasmodium falciparum

pH Stability

EC Number pH Stability pH Stability Maximum Comment Organism
3.4.11.21 6 11 stable when stored for 1 h at 37°C over the pH range 6 to 11 Plasmodium falciparum

Ki Value [mM]

EC Number Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
3.4.11.7 0.00034
-
 (3R)-3-amino-3-phosphonopropanoic acid
-
 Plasmodium falciparum
3.4.11.7 0.0044
-
 (1-aminopropane-1,3-diyl)bis(phosphonic acid)
-
 Plasmodium falciparum
3.4.11.7 0.0271
-
 amino(phosphono)acetic acid
-
 Plasmodium falciparum
3.4.11.7 0.0427
-
 3-[(1-amino-2-carboxyethyl)(hydroxy)phosphoryl]-2-methylpropanoic acid
-
 Plasmodium falciparum
3.4.11.7 0.105
-
 5-amino-5-phosphonopentanoic acid
-
 Plasmodium falciparum
3.4.11.7 0.1831
-
 3-[[amino(carboxy)methyl](hydroxy)phosphoryl]-2-methylpropanoic acid
-
 Plasmodium falciparum
3.4.11.7 0.395
-
 amino[hydroxy(methyl)phosphoryl]acetic acid
-
 Plasmodium falciparum
3.4.11.7 2
-
 3-amino-3-[hydroxy(phenyl)phosphoryl]propanoic acid
-
 Plasmodium falciparum
3.4.11.21 0.00034
-
 4-amino-4-phosphonobutyric acid at pH 7.5 Plasmodium falciparum
3.4.11.21 0.0044
-
 1-amino-1,3-propanediphosphonic acid at pH 7.5 Plasmodium falciparum
3.4.11.21 0.0271
-
 3-amino-3-phosphonopropionic acid at pH 7.5 Plasmodium falciparum
3.4.11.21 0.0427
-
 4-amino-4-[P-(2-carboxypropyl)phosphinyl]butyric acid at pH 7.5 Plasmodium falciparum
3.4.11.21 0.105
-
 5-amino-5-phosphonopentanoic acid at pH 7.5 Plasmodium falciparum
3.4.11.21 0.183
-
 3-amino-3-[P-(2-carboxypropyl)phosphinyl]propionic acid at pH 7.5 Plasmodium falciparum
3.4.11.21 0.395
-
 3-amino-3-(P-methylphosphinyl)propionic acid at pH 7.5 Plasmodium falciparum