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Information on EC 3.4.11.1 - leucyl aminopeptidase and Organism(s) Plasmodium falciparum and UniProt Accession Q8IL11
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3.4.11.1 leucyl aminopeptidaseSpecify your search results
Word Map
- 3.4.11.1
- aminopeptidases
- border
-
brush
- bestatin
- transpeptidase
-
gamma-glutamyl
- maltase
- carboxypeptidase
- sucrase
- urinary
- pregnancy
- bile
- urine
- esterase
- mucosa
-
trim
- chymotrypsin
- transaminase
-
dipeptidyl
- beta-glucuronidase
- 5'-nucleotidase
-
exopeptidase
-
brush-border
-
histocompatibility
- bilirubin
-
nephrotoxicity
- gamma-glutamyltransferase
-
alanyl
-
ankylosing
- spondylitis
- arylamidase
-
jaundice
- p-nitroanilide
-
canalicular
- hepatobiliary
- n-acetyl-beta-glucosaminidase
- gamma-glutamyltranspeptidase
- dipeptidase
- disaccharidase
- oxytocinase
- gamma-gtp
- cholinesterase
-
3.4.11.2
- amastatin
- trehalase
- hepatica
- cellobiohydrolase
-
peptidome
- fasciola
-
enzymuria
- medicine
- synthesis
- pharmacology
- food industry
- drug development
- diagnostics
The taxonomic range for the selected organisms is: Plasmodium falciparum
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
Reaction Schemes
release of an N-terminal amino acid, Xaa-/-Yaa-, in which Xaa is preferably Leu, but may be other amino acids including Pro although not Arg or Lys, and Yaa may be Pro. Amino acid amides and methyl esters are also readily hydrolysed, but rates on arylamides are exceedingly low
release of an N-terminal amino acid, Xaa-/-Yaa-, in which Xaa is preferably Leu, but may be other amino acids including Pro although not Arg or Lys, and Yaa may be Pro. Amino acid mides and methyl esters are also readily hydrolysed, but rates on arylamides are exceedingly low
Synonyms
leucine aminopeptidase, erap2, leucyl aminopeptidase, leucine amino peptidase, l-leucine aminopeptidase, leucinaminopeptidase, pilsap, leucine aminopeptidase 3, leucylaminopeptidase, adipocyte-derived leucine aminopeptidase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
Aminopeptidase A/I
-
-
-
-
cathepsin III
-
-
-
-
cytosol aminopeptidase
-
-
-
-
DR57
-
-
-
-
FTBL proteins
-
-
-
-
L-leucine aminopeptidase
-
-
-
-
LAP
leucinamide aminopeptidase
-
-
-
-
leucinaminopeptidase
-
-
-
-
leucine aminopeptidase
-
-
-
-
Leucyl aminopeptidase
-
-
-
-
leucyl peptidase
-
-
-
-
peptidase S
-
-
-
-
proline aminopeptidase
-
-
-
-
Prolyl aminopeptidase
-
-
-
-
proteins, specific or class, FTBL
-
-
-
-
additional information
-
the enzyme belongs to the peptidase family M17
LAP
-
-
-
-
PATHWAY SOURCE
PATHWAYS
CAS REGISTRY NUMBER
COMMENTARY
9001-61-0
-
90119-07-6
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
Ala-4-methylcoumaryl-7-amide + H2O
Ala + 7-amino-4-methylcoumarin
-
-
-
?
Leu-4-methylcoumaryl-7-amide + H2O
Leu + 7-amino-4-methylcoumarin
-
-
-
?
Phe-4-methylcoumaryl-7-amide + H2O
Phe + 7-amino-4-methylcoumarin
-
-
-
?
Pro-4-methylcoumaryl-7-amide + H2O
Pro + 7-amino-4-methylcoumarin
-
-
-
?
alanyl-7-amido-4-methylcoumarin + H2O
alanine + 7-amino-4-methylcoumarin
-
-
-
-
?
L-leucine-4-methylcoumaryl-7-amide + H2O
L-leucine + 7-amino-4-methylcoumarine
-
-
-
-
?
L-leucyl-7-amido-4-methylcoumarin + H2O
L-leucine + 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
-
-
?
additional information
?
-
-
the enzyme generates and regulates the internal pool of free amino acids and therefore represents a target for antimalarial drugs
-
-
?
additional information
?
-
-
the enzyme is important in the generation and regulation of free amino acids that are used in protein anabolism and for maintaining osmotic stability within the infected erythrocyte, enzyme inhibition, e.g. by bestatin, blocks intraerythrocytic development of malaria parasites
-
-
?
additional information
?
-
-
the enzyme functions in the terminal stages of hemoglobin digestion
-
-
?
additional information
?
-
-
the type of metal ion present at site 1 influences the catalytic efficiency of the enzyme for peptide substrates
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
additional information
?
-
the enzyme generates and regulates the internal pool of free amino acids and therefore represents a target for antimalarial drugs
-
-
?
additional information
?
-
-
the enzyme generates and regulates the internal pool of free amino acids and therefore represents a target for antimalarial drugs
-
-
?
additional information
?
-
-
the enzyme is important in the generation and regulation of free amino acids that are used in protein anabolism and for maintaining osmotic stability within the infected erythrocyte, enzyme inhibition, e.g. by bestatin, blocks intraerythrocytic development of malaria parasites
-
-
?
additional information
?
-
-
the enzyme functions in the terminal stages of hemoglobin digestion
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Co2+
addition of the ion prior to mixing with substrate increases activity up to 24fold
Mg2+
addition of the ion prior to mixing with substrate increases activity up to 8fold
Mn2+
addition of the ion prior to mixing with substrate increases activity up to 24fold
Ni2+
addition of the ion prior to mixing with substrate increases activity up to 10fold
Zn2+
addition of the ion prior to mixing with substrate increases activity up to 4fold
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
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
o-phenanthroline
10 mM, abolishes enzyme activity in presence or absence of Co2+
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
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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
additional information
additional information
-
metal ion binding kinetics to the recombinant enzyme, metal ion occupying site 1 can influence enzyme substrate kinetics, overview
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.000025
bestatin
inhibitory activity against recombinant enzyme
0.000138
bestatin methyl ester
inhibitory activity against recombinant enzyme
0.0000027
nitrobestatin
inhibitory activity against recombinant enzyme
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0205
bestatin methyl ester
Plasmodium falciparum
inhibitory activity against recombinant enzyme
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
PfLAP is produced by all stages in the intra-erythrocytic developmental cycle of malaria but is most highly expressed by trophozoites
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
65000
-
x * 65000, recombinant enzyme, SDS-PAGE, x * 67831, sequence calculation
67831
-
x * 65000, recombinant enzyme, SDS-PAGE, x * 67831, sequence calculation
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
?
-
x * 65000, recombinant enzyme, SDS-PAGE, x * 67831, sequence calculation
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant His-tagged LAP from insect cells by nickel affinity chromatography
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
DNA and amino acid sequence determination and analysis, overexpression of the full-length gene in parasite cytosol, transgenic parasites are more resistant to bestatin
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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
pharmacology
-
the enzyme is a target for the antimalarial activity of inhibitor bestatin
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Gardiner, D.L.; Trenholme, K.R.; Skinner-Adams, T.S.; Stack, C.M.; Dalton, J.P.
Overexpression of leucyl aminopeptidase in Plasmodium falciparum parasites. Target for the antimalarial activity of bestatin
J. Biol. Chem.
281
1741-1745
2006
Plasmodium falciparum
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
J. Biol. Chem.
282
2069-2080
2007
Plasmodium falciparum (Q8IL11), Plasmodium falciparum, Plasmodium falciparum M17 (Q8IL11), Plasmodium falciparum M17
Skinner-Adams, T.S.; Lowther, J.; Teuscher, F.; Stack, C.M.; Grembecka, J.; Mucha, A.; Kafarski, P.; Trenholme, K.R.; Dalton, J.P.; Gardiner, D.L.
Identification of phosphinate dipeptide analog inhibitors directed against the Plasmodium falciparum M17 leucine aminopeptidase as lead antimalarial compounds
J. Med. Chem.
50
6024-6031
2007
Plasmodium falciparum, Plasmodium falciparum M17
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
Biochemistry
48
5435-5439
2009
Plasmodium falciparum
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