Literature summary for 3.4.11.1 extracted from

Stack, C.M.; Lowther, J.; Cunningham, E.; Donnelly, S.; Gardiner, D.L.; Trenholme, K.R.; Skinner-Adams, T.S.; Teuscher, F.; Grembecka, J.; Mucha, A.; Kafarski, P.; Lua, L.; Bell, A.; Dalton, J.P.
Characterization of the Plasmodium falciparum M17 leucyl aminopeptidase. A protease involved in amino acid regulation with potential for antimalarial drug development (2007), J. Biol. Chem., 282, 2069-2080.

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Application

Application	Comment	Organism
medicine	antimalarial activity of aminopeptidase inhibitors	Plasmodium falciparum

Cloned(Commentary)

Cloned (Comment)	Organism
expression in Sf9 cells	Plasmodium falciparum

Inhibitors

Inhibitors	Comment	Organism	Structure
bestatin	antimalarial activity of aminopeptidase inhibitors	Plasmodium falciparum
bestatin methyl ester	-	Plasmodium falciparum
Cu2+	1.0 mM	Plasmodium falciparum
EDTA	10 mM inhibition	Plasmodium falciparum
nitrobestatin	-	Plasmodium falciparum
o-phenanthroline	10 mM, abolishes enzyme activity in presence or absence of Co2+	Plasmodium falciparum

KM Value [mM]

KM Value [mM]	KM Value Maximum [mM]	Substrate	Comment	Organism	Structure
0.00792	-	Phe-4-methylcoumaryl-7-amide	-	Plasmodium falciparum
0.01212	-	Leu-4-methylcoumaryl-7-amide	-	Plasmodium falciparum
0.0529	-	Ala-4-methylcoumaryl-7-amide	-	Plasmodium falciparum
0.2349	-	Pro-4-methylcoumaryl-7-amide	-	Plasmodium falciparum

Metals/Ions

Metals/Ions	Comment	Organism	Structure
Co2+	addition of the ion prior to mixing with substrate increases activity up to 24fold	Plasmodium falciparum
Mg2+	addition of the ion prior to mixing with substrate increases activity up to 8fold	Plasmodium falciparum
Mn2+	addition of the ion prior to mixing with substrate increases activity up to 24fold	Plasmodium falciparum
Ni2+	addition of the ion prior to mixing with substrate increases activity up to 10fold	Plasmodium falciparum
Zn2+	addition of the ion prior to mixing with substrate increases activity up to 4fold	Plasmodium falciparum

Molecular Weight [Da]

Molecular Weight [Da]	Molecular Weight Maximum [Da]	Comment	Organism
60000	-	6 * 60000, SDS-PAGE	Plasmodium falciparum
320000	-	gel filtration	Plasmodium falciparum

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.	Reac.
additional information	Plasmodium falciparum	the enzyme generates and regulates the internal pool of free amino acids and therefore represents a target for antimalarial drugs	?	-	?
additional information	Plasmodium falciparum M17	the enzyme generates and regulates the internal pool of free amino acids and therefore represents a target for antimalarial drugs	?	-	?

Organism

Organism	UniProt	Comment	Textmining
Plasmodium falciparum	Q8IL11	-	-
Plasmodium falciparum M17	Q8IL11	-	-

Purification (Commentary)

Purification (Comment)	Organism
-	Plasmodium falciparum

Source Tissue

Source Tissue	Comment	Organism	Textmining
trophozoite	PfLAP is produced by all stages in the intra-erythrocytic developmental cycle of malaria but is most highly expressed by trophozoites	Plasmodium falciparum	-

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
Ala-4-methylcoumaryl-7-amide + H2O	-	Plasmodium falciparum	Ala + 7-amino-4-methylcoumarin	-	?
Ala-4-methylcoumaryl-7-amide + H2O	-	Plasmodium falciparum M17	Ala + 7-amino-4-methylcoumarin	-	?
Leu-4-methylcoumaryl-7-amide + H2O	-	Plasmodium falciparum	Leu + 7-amino-4-methylcoumarin	-	?
Leu-4-methylcoumaryl-7-amide + H2O	-	Plasmodium falciparum M17	Leu + 7-amino-4-methylcoumarin	-	?
additional information	the enzyme generates and regulates the internal pool of free amino acids and therefore represents a target for antimalarial drugs	Plasmodium falciparum	?	-	?
additional information	the enzyme generates and regulates the internal pool of free amino acids and therefore represents a target for antimalarial drugs	Plasmodium falciparum M17	?	-	?
Phe-4-methylcoumaryl-7-amide + H2O	-	Plasmodium falciparum	Phe + 7-amino-4-methylcoumarin	-	?
Phe-4-methylcoumaryl-7-amide + H2O	-	Plasmodium falciparum M17	Phe + 7-amino-4-methylcoumarin	-	?
Pro-4-methylcoumaryl-7-amide + H2O	-	Plasmodium falciparum	Pro + 7-amino-4-methylcoumarin	-	?
Pro-4-methylcoumaryl-7-amide + H2O	-	Plasmodium falciparum M17	Pro + 7-amino-4-methylcoumarin	-	?

Subunits

Subunits	Comment	Organism
hexamer	6 * 60000, SDS-PAGE	Plasmodium falciparum

Synonyms

Synonyms	Comment	Organism
PfLAP	-	Plasmodium falciparum

Turnover Number [1/s]

Turnover Number Minimum [1/s]	Turnover Number Maximum [1/s]	Substrate	Comment	Organism	Structure
0.0002	-	Ala-4-methylcoumaryl-7-amide	-	Plasmodium falciparum
0.00059	-	Pro-4-methylcoumaryl-7-amide	-	Plasmodium falciparum
0.00145	-	Phe-4-methylcoumaryl-7-amide	-	Plasmodium falciparum
0.039	-	Leu-4-methylcoumaryl-7-amide	-	Plasmodium falciparum

pH Optimum

pH Optimum Minimum	pH Optimum Maximum	Comment	Organism
8.5	-	-	Plasmodium falciparum

Ki Value [mM]

Ki Value [mM]	Ki Value maximum [mM]	Inhibitor	Comment	Organism	Structure
0.0000027	-	nitrobestatin	inhibitory activity against recombinant enzyme	Plasmodium falciparum
0.000025	-	bestatin	inhibitory activity against recombinant enzyme	Plasmodium falciparum
0.000138	-	bestatin methyl ester	inhibitory activity against recombinant enzyme	Plasmodium falciparum

IC50 Value

IC50 Value	IC50 Value Maximum	Comment	Organism	Inhibitor	Structure
0.008	-	inhibitory activity against recombinant enzyme	Plasmodium falciparum	nitrobestatin
0.0149	-	inhibitory activity against recombinant enzyme	Plasmodium falciparum	bestatin
0.0205	-	inhibitory activity against recombinant enzyme	Plasmodium falciparum	bestatin methyl ester

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Release 2023.1 (January 2023)