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Information on EC 3.4.11.20 - aminopeptidase Ey
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3.4.11.20 aminopeptidase EySpecify your search results
Word Map
- 3.4.11.20
- plasmodium
- falciparum
-
antimalarial
- aminopeptidases
- bestatin
- hemoglobin
- dipeptide
-
malarial
-
subsite
-
metalloaminopeptidases
- yolk
-
hydroxamic
- gallus
-
leucyl
-
exopeptidases
- domesticus
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
Reaction Schemes
differs from other aminopeptidases in broad specificity for amino acids in the P1 position and the ability to hydrolyse peptides of four or five residues that contain Pro in the P1' position
Synonyms
pfa-m1, pfa-m17, aminopeptidase ey, pf-lap, m1-family aminopeptidase, pfa-m1 aminopeptidase, 
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
M1 aminopeptidase
PfA-M1
PfA-M1
-
belongs to the M1 family and displays a strict aminopeptidase activity at pH 7.4 and a broad substrate spectrum
PfA-M1
-
belongs to the M1 family and displays a strict aminopeptidase activity at pH 7.4 and a broad substrate spectrum
-
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
differs from other aminopeptidases in broad specificity for amino acids in the P1 position and the ability to hydrolyse peptides of four or five residues that contain Pro in the P1' position
differs from other aminopeptidases in broad specificity for amino acids in the P1 position and the ability to hydrolyse peptides of four or five residues that contain Pro in the P1' position
-
-
-
-
differs from other aminopeptidases in broad specificity for amino acids in the P1 position and the ability to hydrolyse peptides of four or five residues that contain Pro in the P1' position
Glu387 is an essential catalytic residue
-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of peptide bond
-
-
exopeptidase
-
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CAS REGISTRY NUMBER
COMMENTARY
9031-94-1
-
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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
(S)-2-amino-4-cyclohexylbutanoyl-7-amido-4-methylcoumarin + H2O
(S)-2-amino-4-cyclohexylbutanoic acid + 7-amino-4-methylcoumarin
-
-
-
?
Ala-7-amido-4-methylcoumarin + H2O
alanine + 7-amino-4-methylcoumarin
-
-
-
?
Arg-Pro-Pro-Gly-Phe + H2O
Arg + Pro-Pro-Gly-Phe
-
bradikinin fragment 1-5, no hydrolysis of bradikinin
-
?
cholecystokinin octapeptide + H2O
tyrosine sulfate + Asp + Met + Gly + Trp + Met-Asp-Phe-NH2
-
i.e. Asp-tyrosyl sulfate-Met-Gly-Trp-Met-Asp-Phe-NH2
-
-
?
Gly-p-nitroanilide + H2O
Gly + p-nitroaniline
-
58.5% activity compared to L-Pro-p-nitroanilide
-
-
?
homoargininyl-7-amido-4-methylcoumarin + H2O
homoarginine + 7-amino-4-methylcoumarin
-
-
-
?
homophenylalanyl-7-amido-4-methylcoumarin + H2O
homophenylalanine + 7-amino-4-methylcoumarin
-
-
-
?
L-Ala-p-nitroanilide + H2O
L-Ala + p-nitroaniline
-
55.4% activity compared to L-Pro-p-nitroanilide
-
-
?
L-alanyl-2-naphthylamide + H2O
L-alanine + 2-naphthylamine
-
-
-
?
L-arginyl-2-naphthylamide + H2O
L-arginine + 2-naphthylamine
-
-
-
?
L-His-2-naphthylamide + H2O
L-His + 2-naphthylamine
-
31.6% activity compared to L-Pro-p-nitroanilide
-
-
?
L-Ile-2-naphthylamide + H2O
L-Ile + 2-naphthylamine
-
4.6% activity compared to L-Pro-p-nitroanilide
-
-
?
L-Leu-7-amido-4-methyl-coumarin + H2O
L-leucine + 7-amino-4-methyl-coumarin
-
-
-
?
L-Leu-7-amido-4-methylcoumarin + H2O
L-leucine + 7-amino-4-methylcoumarin
-
-
-
?
L-Lys-p-nitroanilide + H2O
L-Lys + p-nitroaniline
-
13% activity compared to L-Pro-p-nitroanilide
-
-
?
L-Met-p-nitroanilide + H2O
L-Met + p-nitroaniline
-
11.5% activity compared to L-Pro-p-nitroanilide
-
-
?
L-methionyl-7-amido-4-methylcoumarin + H2O
L-methionine + 7-amino-4-methylcoumarin
-
-
-
?
L-Phe-p-nitroanilide + H2O
L-Phe + p-nitroaniline
-
1.1% activity compared to L-Pro-p-nitroanilide
-
-
?
L-Pro-2-naphthylamide + H2O
L-Pro + 2-naphthylamine
-
100% activity
-
-
?
L-Pro-p-nitroanilide + H2O
L-Pro + p-nitroaniline
-
100% activity
-
-
?
L-Ser-2-naphthylamide + H2O
L-Ser + 2-naphthylamine
-
64% activity compared to L-Pro-2-naphthylamide
-
-
?
L-Trp-2-naphthylamide + H2O
L-Trp + 2-naphthylamine
-
15.6% activity compared to L-Pro-p-nitroanilide
-
-
?
L-Tyr-2-naphthylamide + H2O
L-Tyr + 2-naphthylamine
-
30.3% activity compared to L-Pro-p-nitroanilide
-
-
?
L-Val-p-nitroanilide + H2O
L-Val + p-nitroaniline
-
5.3% activity compared to L-Pro-p-nitroanilide
-
-
?
Leu-enkephalin + H2O
?
-
i.e. Tyr-Gly-Gly-Phe-Met, stepwise degradation from the N-terminus
-
-
?
Leu-Pro-Leu-Arg-Phe-NH2 + H2O
Leu + Pro-Leu-Arg-Phe-NH2
-
a chicken brain pentapeptide
-
-
?
Leu-Pro-Leu-Arg-PheNH2 + H2O
Leu + Pro-Leu-Arg-PheNH2
-
i.e. chicken brain peptide
resistant to the enzyme
?
Lys-Phe-Ile-Gly-Leu-Met-NH2 + H2O
?
-
eledoisin-related peptide, lysine, phenylalanine, isoleucine, glycine and leucine are liberated from the aminoterminus, methionine is not released from Met-NH2 of the final product
-
-
?
norleucyl-7-amido-4-methylcoumarin + H2O
norleucine + 7-amino-4-methylcoumarin
-
-
-
?
norvalinyl-7-amido-4-methylcoumarin + H2O
norvaline + 7-amino-4-methylcoumarin
-
-
-
?
styryl-Ala-7-amido-4-methylcoumarin + H2O
styryl-alanine + 7-amino-4-methylcoumarin
-
-
-
?
Arg-Pro-Lys-Pro + H2O
Arg + Pro-Lys-Pro
-
i.e. , substance P fragment 1-4, hydrolysis of the N-terminal Xaa-bond, no hydrolysis of substance P
-
?
L-Leu-p-nitroanilide + H2O
L-Leu + p-nitroaniline
-
8.2% activity compared to L-Pro-p-nitroanilide
-
-
?
L-leucyl-7-amido-4-methylcoumarin + H2O
L-leucine + 7-amino-4-methylcoumarin
-
-
-
-
?
L-leucyl-7-amido-4-methylcoumarin + H2O
L-leucine + 7-amino-4-methylcoumarin
-
-
-
?
additional information
?
-
-
broad specificity for amino acid residues at P1 position, not: Pro-Leu-GlyNH2, schistoFMRF-amide (Pro-Asp-Val-Asp-His-Val-Phe-Leu-Arg-PheNH2), melanocyte-stimulating hormone release-inhibiting factor, Leu-Pro-Thr, Lys-Pro-Arg, Ala-Pro, Gly-Pro, Leu-Pro, Met-Pro, Phe-Pro, alpha-bag cell peptide (Ala-Pro-Arg-Leu-Arg-Phe-Tyr-Ser-Leu)
-
-
?
additional information
?
-
-
the enzyme functiones in regulation of hormone function and thus is involved in diverse biological processes, it offers a biodefense against the infectious microbial product N-formyl-peptide
-
-
?
additional information
?
-
-
the enzyme has a broad specificity for N-terminal amino acids residues at the P1 position of substrates, it degrades hydrophobic, basic, and acidic amino acids including proline, no activity with substance P and melanocyte-stimulating hormone release-inhibiting factor, i.e. Pro-Leu-Gly-NH2
-
-
?
additional information
?
-
-
both S1 and S1' subsite exhibit a preference for basic and hydrophobic side chains over polar and acidic side chains. The relative specificity of the S1 subsite is similar over the pH range 5.5-7.5. Substrate P1 and P1' residues affect both Km and kcat, revealing that side chain-subsite interactions not only drive the formation of the Michaelis complex but also influence the rates of ensuing chemical steps. There is no correlation between S1 and S1' specificities and amino acid abundance in hemoglobin. Interactions between PfA-M1 and the backbone atoms of the P1' and P2' residues as well as the P2' side chain further contribute to the catalytic efficiency of substrate hydrolysis
-
-
?
additional information
?
-
no substrates: Ile-4-nitroanilide, Val-4-nitroanilide, Gly-4-nitroanilide, Pro-4-nitroanilide
-
-
?
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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 functiones in regulation of hormone function and thus is involved in diverse biological processes, it offers a biodefense against the infectious microbial product N-formyl-peptide
-
-
?
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ca2+
Cd2+
Co2+
Cu2+
Mn2+
Ni2+
Zinc
Zn2+
additional information
Zn2+
treatment with 1,10-phenanthroline in order to deplete metal ions, results in a residual activity of about 8% compared to the initial activity. Activity is partially restored by the addition of divalent metal cations with Zn2+ being the most potent
Zn2+
-
activates, required for activity and stability, zinc is bound by residues His386, His390, and Glu409
additional information
-
no activation of the inactive, Zn2+-free apoenzyme by Mg2+ and Fe2+
additional information
-
the enzyme is a metalloenzyme, the apoenzyme is inactive
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(2S,17S,20S,21R)-21-amino-5-(4-benzoylbenzyl)-2-[4-(hex-5-ynoylamino)butyl]-20-hydroxy-17-(naphthalen-2-ylmethyl)-4,7,16,19-tetraoxo-22-phenyl-9,12-dioxa-3,6,15,18-tetraazadocosan-1-amide
-
1-hydroxy-2-oxo-1,2-dihydro-quinoline-3-carboxylic acid (4-phenyl-butyl)-amide
-
-
1-hydroxy-2-oxo-1,2-dihydro-quinoline-3-carboxylic acid 4-fluoro-benzylamide
-
-
2-(4-benzyl-piperidine-1-carbonyl)-4-methyl-pentanoic acid hydroxyamide
-
-
2-benzyl-3-(3,4-dihydro-1H-isoquinolin-2-yl)-N-hydroxy-3-oxo-propionamide
-
-
3-(3,4-dihydro-1H-isoquinolin-2-yl)-N-hydroxy-3-oxo-2-(3-phenoxy-benzyl)-propionamide
-
-
3-(4-benzyl-piperidin-1-yl)-N-hydroxy-3-oxo-2-(3-phenoxybenzyl)-propionamide
-
-
N-(1-(4-(1H-pyrazol-1-yl)phenyl)-2-(hydroxyamino)-2-oxoethyl)-3-aminobenzamide
highly effective against the malaria parasites, IC50 values of 233 nM; highly effective against the malaria parasites, IC50 values of 233 nM
N-(1-(4-(1H-pyrazol-1-yl)phenyl)-2-(hydroxyamino)-2-oxoethyl)-4-aminobenzamide
highly effective against the malaria parasites, IC50 values of 283 nM; highly effective against the malaria parasites, IC50 values of 283 nM
N-(1-(4-(1H-pyrazol-1-yl)phenyl)-2-(hydroxyamino)-2-oxoethyl)-pivalamide
most effective inhibitor of isoform M1 and one of the more potent inhibitors of isoform M17 tested, the most effective compound against 3D7 malaria parasites, with an IC50 of 227 nM; most effective inhibitor of isoform M1 and one of the more potent inhibitors of isoform M17 tested, the most effective compound against 3D7 malaria parasites, with an IC50 of 227 nM
N-(4-fluoro-benzyl)-N'-hydroxy-2-[1-phenyl-meth-(E)-ylidene]-malonamide
-
-
N-(4-fluoro-benzyl)-N'-hydroxy-2-[1-phenyl-meth-(Z)-ylidene]-malonamide
-
-
N-benzyl-N'-hydroxy-2-isobutyl-malonamide
-
in Tris-HCl buffer (25 mM, pH 7.4), at 25°C
N-hydroxy-2-(3-phenoxy-benzyl)-N'-(4-trifluoromethyl-benzyl)-malonamide
-
-
N-hydroxy-2-isobutyl-N'-(1,2,3,4-tetrahydro-naphthalen-1-yl)-malonamide
-
-
N-hydroxy-N'-(4-phenyl-butyl)-2-[1-phenyl-meth-(Z)-ylidene]-malonamide
-
-
N-[(2-[2-[(N-[(2S,3R)-3-amino-4-[4-(benzyloxy)phenyl]-2-hydroxybutanoyl]-L-alanyl)amino]ethoxy]ethoxy)acetyl]-4-benzoylphenylalanyl-N6-hex-5-ynoyl-L-lysinamide
-
N-[(2S,3R)-3-amino-2-hydroxy-4-(4-methoxyphenyl)butanoyl]-L-leucine
-
-
N-[(2S,3R)-3-amino-2-hydroxy-4-(naphthalen-2-yl)butanoyl]-L-leucine
-
-
N-[(2S,3R)-3-amino-4-[4-(benzyloxy)phenyl]-2-hydroxybutanoyl]-L-leucine
-
-
N2-[(2S,3R)-3-amino-2-hydroxy-4-phenylbutanoyl]-N6-[(benzyloxy)carbonyl]-L-lysine
-
-
tert-butyl (1-(4-(1H-Pyrazol-1-yl)phenyl)-2-(hydroxyamino)-2-oxoethyl)carbamate
compound shows good in vitro inhibitory properties, but IC50 for parasite growth is only 783 nM, suggesting that compounds substituted with the N-Boc group are either less capable of cellular penetration or less stable than the corresponding N-acyl derivatives; compound shows good in vitro inhibitory properties, but IC50 for parasite growth is only 783 nM, suggesting that compounds substituted with the N-Boc group are either less capable of cellular penetration or less stable than the corresponding N-acyl derivatives
tosedostat
i.e. (2S)-([(2R)-2-[(1S)-1-hydroxy-2-(hydroxyamino)-2-oxoethyl]-4-methylpentanoyl]amino)(phenyl)ethanoic acid, crystal structure; i.e. (2S)-({(2R)-2-[(1S)-1-hydroxy-2-(hydroxyamino)-2-oxoethyl]-4-methylpentanoyl}amino)(phenyl)ethanoic acid, crystal structure
1,10-phenanthroline
treatment with 1,10-ortho-phenanthroline in order to deplete metal ions, results in a residual activity of about 8% compared to the initial activity. Activity is partially restored by the addition of divalent metal cations with Zn2+ being the most potent
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DISEASE
TITLE OF PUBLICATION
LINK TO PUBMED
Anemia
IgG antibody response against Plasmodium falciparum aminopeptidase 1 antigen in Gabonese children living in Makokou and Franceville.
Infections
IgG antibody response against Plasmodium falciparum aminopeptidase 1 antigen in Gabonese children living in Makokou and Franceville.
Infections
Two-pronged attack: dual inhibition of Plasmodium falciparum M1 and M17 metalloaminopeptidases by a novel series of hydroxamic acid-based inhibitors.
Malaria
Distribution and Biochemical Properties of an M1-family Aminopeptidase in Plasmodium falciparum Indicate a Role in Vacuolar Hemoglobin Catabolism.
Malaria
KBE009: An antimalarial bestatin-like inhibitor of the Plasmodium falciparum M1 aminopeptidase discovered in an Ugi multicomponent reaction-derived peptidomimetic library.
Malaria
Selective inhibition of PfA-M1, over PfA-M17, by an amino-benzosuberone derivative blocks malaria parasites development in vitro and in vivo.
Malaria
Structure of the Plasmodium falciparum M17 aminopeptidase and significance for the design of drugs targeting the neutral exopeptidases.
Malaria
Synthesis and structure-activity relationships of phosphonic arginine mimetics as inhibitors of the M1 and M17 aminopeptidases from Plasmodium falciparum.
Malaria
Synthesis of new (-)-bestatin-based inhibitor libraries reveals a novel binding mode in the s1 pocket of the essential malaria m1 metalloaminopeptidase.
Malaria
Two cap residues in the S1 subsite of a Plasmodium falciparum M1-family aminopeptidase promote broad specificity and enhance catalysis.
Malaria
X-ray crystal structures of an orally available aminopeptidase inhibitor, Tosedostat, bound to anti-malarial drug targets PfA-M1 and PfA-M17.
Malaria, Falciparum
X-ray crystal structures of an orally available aminopeptidase inhibitor, Tosedostat, bound to anti-malarial drug targets PfA-M1 and PfA-M17.
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0236
(S)-2-amino-4-cyclohexylbutanoyl-7-amido-4-methylcoumarin
pH 7.4, 37°C
0.17
L-arginyl-2-naphthylamide
recombinant protein, pH 7.5, 37°C
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.737
(S)-2-amino-4-cyclohexylbutanoyl-7-amido-4-methylcoumarin
pH 7.4, 37°C