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Literature summary for 3.4.11.1 extracted from

  • Maric, S.; Donnelly, S.M.; Robinson, M.W.; Skinner-Adams, T.; Trenholme, K.R.; Gardiner, D.L.; Dalton, J.P.; Stack, C.M.; Lowther, J.
    The M17 leucine aminopeptidase of the malaria parasite Plasmodium falciparum: importance of active site metal ions in the binding of substrates and inhibitors (2009), Biochemistry, 48, 5435-5439.
    View publication on PubMed
Search for more literature for 3.4.11.1

Application

Application Comment Organism
drug development the enzyme represents a target for which antimalarials can be designed since metalloaminopeptidase inhibitors prevent the growth of the parasites in vitro and in vivo Plasmodium falciparum

Cloned(Commentary)

Cloned (Comment) Organism
His-tagged LAP expression in insect cells Plasmodium falciparum

Inhibitors

Inhibitors Comment Organism Structure
bestatin a metal-chelating inhibitor of M17 aminopeptidases with antimalarial activity, the type of metal ion present at site 1 influences the mode of binding by bestatin Plasmodium falciparum
EDTA
-
 Plasmodium falciparum

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
additional information
-
 additional information metal ion binding kinetics to the recombinant enzyme, metal ion occupying site 1 can influence enzyme substrate kinetics, overview Plasmodium falciparum
0.35
-
 L-leucine-4-methylcoumaryl-7-amide pH 8.0, 37°C, recombinant enzyme in presence of Zn2+ and Mg2+, best ion combination at metal binding sites 1 and 2 Plasmodium falciparum

Localization

Localization Comment Organism GeneOntology No. Textmining
cytosol
-
 Plasmodium falciparum 5829
-

Metals/Ions

Metals/Ions Comment Organism Structure
Co2+ binds at metal site 1 Plasmodium falciparum
Mg2+ binds at metal site 1 Plasmodium falciparum
Mn2+ binds at metal site 1 Plasmodium falciparum
additional information the exopeptidase contains two metal-binding sites, a readily exchangeable site and a tight binding site. The enzyme retains activity when the metal ion is removed from site 1, while removal of metal ions from both sites results in an inactive apoenzyme that cannot be reactivated by the addition of divalent metal cations. The metal ion at site 1 is readily exchangeable with several divalent metal ions and displays a preference in the order of preference Zn2+, Mn2+, Co2+, Mg2+. While it is likely that native PfLAP contains a Zn2+ in site 2. the type of metal ion present at site 1 influences not only the catalytic efficiency of the enzyme for peptide substrates but also the mode of binding by bestatin, a metal-chelating inhibitor of M17 aminopeptidases with antimalarial activity Plasmodium falciparum
Zn2+ binds at metal sites 1 and 2 Plasmodium falciparum

Organism

Organism UniProt Comment Textmining
Plasmodium falciparum
-
-
-

Purification (Commentary)

Purification (Comment) Organism
recombinant His-tagged LAP from insect cells by nickel affinity chromatography Plasmodium falciparum

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
L-leucine-4-methylcoumaryl-7-amide + H2O
-
 Plasmodium falciparum L-leucine + 7-amino-4-methylcoumarine
-
 ?
additional information the type of metal ion present at site 1 influences the catalytic efficiency of the enzyme for peptide substrates Plasmodium falciparum ?
-
 ?

Synonyms

Synonyms Comment Organism
LAP
-
 Plasmodium falciparum
M17 leucine aminopeptidase
-
 Plasmodium falciparum

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
37
-
 assay at Plasmodium falciparum

Turnover Number [1/s]

Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
0.0094
-
 L-leucine-4-methylcoumaryl-7-amide pH 8.0, 37°C, recombinant enzyme in presence of Zn2+ and Mg2+, best ion combination at metal binding sites 1 and 2 Plasmodium falciparum

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
8
-
 assay at Plasmodium falciparum

General Information

General Information Comment Organism
physiological function the M17 leucine aminopeptidase of the intraerythrocytic stages of the malaria parasite Plasmodium falciparum plays a role in releasing amino acids from host hemoglobin that are used for parasite protein synthesis, growth, and development Plasmodium falciparum

kcat/KM [mM/s]

kcat/KM Value [1/mMs-1] kcat/KM Value Maximum [1/mMs-1] Substrate Comment Organism Structure
0.0027
-
 L-leucine-4-methylcoumaryl-7-amide pH 8.0, 37°C, recombinant enzyme in presence of Zn2+ and Mg2+, best ion combination at metal binding sites 1 and 2 Plasmodium falciparum