Information on EC 3.4.11.9 - Xaa-Pro aminopeptidase

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The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea

EC NUMBER
COMMENTARY
3.4.11.9
-
RECOMMENDED NAME
GeneOntology No.
Xaa-Pro aminopeptidase
-
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
release of any N-terminal amino acid, including proline, that is linked to proline, even from a dipeptide or tripeptide
show the reaction diagram
mechanism, cis-trans specificity
-
release of any N-terminal amino acid, including proline, that is linked to proline, even from a dipeptide or tripeptide
show the reaction diagram
-
-
-
-
release of any N-terminal amino acid, including proline, that is linked to proline, even from a dipeptide or tripeptide
show the reaction diagram
acive site configuration, modeling, Asp449, Asp460, His523, Glu554, and Glu568 are in volved in metal binding in the active site, His429 and His523 are involved in shuttling protons during catalysis
-
release of any N-terminal amino acid, including proline, that is linked to proline, even from a dipeptide or tripeptide
show the reaction diagram
isozyme APP-2 shows a preference for Arg-Pro-Pro-, Arg-Pro-Lys-, Pro-Pro-Gly-, -Phe-Gly- in descending order
release of any N-terminal amino acid, including proline, that is linked to proline, even from a dipeptide or tripeptide
show the reaction diagram
R404 participates in proton relay and in the hydrogen bond network
-
release of any N-terminal amino acid, including proline, that is linked to proline, even from a dipeptide or tripeptide
show the reaction diagram
H243 stabilizes substrate binding, H361 stabilizes substrate binding and the gem-diol catalytic intermediate. H350 forms part of a hydrophobic binding pocket that gives the enzyme its proline specificity
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of peptide bond
-
-
exopeptidase, N-terminus, amino acid
-
SYNONYMS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
aminoacylproline aminopeptidase
-
-
-
-
aminopeptidase P
-
-
-
-
aminopeptidase P
-
-
aminopeptidase P
-
-
aminopeptidase P
-
aminopeptidase P
-
-
aminopeptidase P
-
-
aminopeptidase P
-
-
aminopeptidase P
-
aminopeptidase P
-
-
aminopeptidase P
-
-
aminopeptidase P1
-
-
aminopeptidase, aminoacylproline
-
-
-
-
AP-P
-
-
-
-
AP-P
-
-
APP
-
-
-
-
APP1
-
-
dapUm
-
gene name
ecAPP
-
ortholog of human X-prolyl aminopeptidase 3 (xpnpep3)
hAPP1
-
-
mAmP
-
-
-
-
Membrane-bound AmP
-
-
-
-
proline aminopeptidase
-
-
-
-
X-Pro aminopeptidase
-
-
-
-
X-Pro aminopeptidase
-
-
X-Pro aminopeptidase
-
X-Pro aminopeptidase
-
-
X-prolyl aminopeptidase
-
-
X-prolyl aminopeptidase 3
-
-
X-prolyl aminopeptidase 3
-
X-prolyl-dipeptidyl aminopeptidase
-
-
Xaa-Pro aminopeptidase
-
-
-
-
Xaa-Pro dipeptidase
-
-
XPNPEP1
-
-
XPNPEP3
-
-
Membrane-bound APP
-
-
-
-
additional information
-
the enzyme belongs to the peptidase family M24
additional information
the enzyme belongs to the peptidase family M24
additional information
-
the enzyme belongs to the peptidase family M24
additional information
-
the enzyme belongs to the peptidase family M24
additional information
the enzyme belongs to the peptidase family M24
additional information
-
the enzyme belongs to the peptidase family M24
additional information
the enzyme belongs to the peptidase family M24
additional information
-
the enzyme belongs to the peptidase family M24
CAS REGISTRY NUMBER
COMMENTARY
37288-66-7
-
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
calf
-
-
Manually annotated by BRENDA team
cytosolic isoform
SwissProt
Manually annotated by BRENDA team
HB101, 2 types of enzyme: APP-I and APP-II
-
-
Manually annotated by BRENDA team
-
SwissProt
Manually annotated by BRENDA team
subsp. cremonis AM2
-
-
Manually annotated by BRENDA team
Fischer F344
-
-
Manually annotated by BRENDA team
wild type and mutant strain that lacks peptidase P
-
-
Manually annotated by BRENDA team
gene LeAPP1, isozyme APP1
SwissProt
Manually annotated by BRENDA team
gene LeAPP2, isozyme APP2
SwissProt
Manually annotated by BRENDA team
strain TH-4
SwissProt
Manually annotated by BRENDA team
Streptomyces costaricanus TH-4
strain TH-4
SwissProt
Manually annotated by BRENDA team
isoform APP II
-
-
Manually annotated by BRENDA team
strain NA1, expressed in Escherichia coli
SwissProt
Manually annotated by BRENDA team
Thermococcus sp. NA1
strain NA1, expressed in Escherichia coli
SwissProt
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
-
suppression of zebrafish xpnpep3 phenocopied the developmental phenotypes of ciliopathy morphants, and this effect is rescued by human XPNPEP3 that is devoid of a mitochondrial localization signal, suggesting that the protein might also have mitochondrial-independent activity
malfunction
in 2 families with an nephronophthisis-like phenotype, homozygous frameshift and splice-site mutations, respectively, are detected in the X-prolyl aminopeptidase 3 gene
malfunction
-
Xpnpep1 knockout mice display severe growth retardation, microcephaly, and modest lethality. Imino-oligopeptide excretion is observed in urine samples from APP1-deficient mice
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
(2-aminobenzoyl)-Lys-Pro-Pro-4-nitroanilide + H2O
?
show the reaction diagram
-
-
-
-
?
(4-nitro)Phe-Pro-HN-CH2-CH2-NH-o-aminobenzoyl + H2O
(4-nitro)Phe + Pro-HN-CH2-CH2-NH-o-aminobenzoyl
show the reaction diagram
-
-
-
?
(4-nitro)Phe-Pro-Pro-HN-CH2-CH2-NH-o-aminobenzoyl + H2O
(4-nitro)Phe + Pro-Pro-HN-CH2-CH2-NH-o-aminobenzoyl
show the reaction diagram
-
-
-
?
2-aminobenzoyl-L-Lys-L-Pro-L-Pro-4-nitroanilide + H2O
?
show the reaction diagram
-
-
-
-
?
Abz-L-Lys-L-Pro-L-Pro-4-nitroanilide + H2O
Abz-L-Lys + L-Pro-L-Pro-4-nitroanilide
show the reaction diagram
-
-
-
?
Abz-L-Lys-L-Pro-L-Pro-4-nitroanilide + H2O
Abz-L-Lys + L-Pro-L-Pro-4-nitroanilide
show the reaction diagram
Thermococcus sp., Thermococcus sp. NA1
-
-
?
Abz-L-Lys-L-Pro-L-Pro-p-nitroanilide + H2O
Abz-L-Lys + L-Pro-L-Pro-p-nitroanilide
show the reaction diagram
-
-
-
?
Ala-Pro + H2O
Ala + Pro
show the reaction diagram
-
-
-
?
Ala-Pro + H2O
Ala + Pro
show the reaction diagram
-
-
-
?
Ala-Pro + H2O
Ala + Pro
show the reaction diagram
-
-
-
?
Ala-Pro-4-nitroanilide + H2O
Ala + Pro-4-nitroanilide
show the reaction diagram
-
-
-
?
Ala-Pro-Gly + H2O
Ala + Pro-Gly
show the reaction diagram
-
-
-
?
Ala-Pro-Gly + H2O
Ala + Pro-Gly
show the reaction diagram
-
-
-
?
Ala-Pro-p-nitroanilide + H2O
Ala + Pro-p-nitroanilide
show the reaction diagram
-
-
-
?
allostatin 1 + H2O
Ala + ?
show the reaction diagram
-
-
cleavage of the Ala1-Pro2 bond
?
APKPKFIRF-amide + H2O
?
show the reaction diagram
-
-
-
-
?
Arg-homoPro-Pro-Ala-NH2 + H2O
?
show the reaction diagram
-
-
-
-
?
Arg-Pro + H2O
Arg + Pro
show the reaction diagram
-
-
-
?
Arg-Pro-Lys-Pro + H2O
?
show the reaction diagram
-
-
-
-
?
Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Leu-Gly-Met-NH2 + H2O
?
show the reaction diagram
-
-
-
-
?
Arg-Pro-Pro + H2O
Arg + Pro-Pro
show the reaction diagram
-
-
-
?
Arg-Pro-Pro + H2O
Arg + Pro-Pro
show the reaction diagram
-
-
-
?
Arg-Pro-Pro + H2O
Arg + Pro-Pro
show the reaction diagram
-
-
-
?
Arg-Pro-Pro + H2O
Arg + Pro-Pro
show the reaction diagram
-
-
-
?
Arg-Pro-Pro + H2O
Arg + Pro-Pro
show the reaction diagram
-
-
-
?
Arg-Pro-Pro + H2O
Arg + Pro-Pro
show the reaction diagram
-
-
-
?
Arg-Pro-Pro + H2O
Arg + Pro-Pro
show the reaction diagram
-
-
-
?
Arg-Pro-Pro-benzylamide + H2O
Arg + Pro-Pro-benzylamide
show the reaction diagram
-
-
-
?
Arg-Pro-Pro-Gly-Phe + H2O
?
show the reaction diagram
-
-
-
-
-
Arg-Pro-Pro-Gly-Phe + H2O
?
show the reaction diagram
-
-
-
-
?
Arg-Pro-Pro-Gly-Phe-Ser + H2O
?
show the reaction diagram
-
-
-
-
-
Arg-Pro-Pro-Gly-Phe-Ser + H2O
?
show the reaction diagram
-
-
-
-
?
Arg-Pro-Pro-Gly-Phe-Ser + H2O
?
show the reaction diagram
-
-
-
-
?
Arg-Pro-Pro-Gly-Phe-Ser-Pro + H2O
?
show the reaction diagram
-
-
-
-
-
Arg-Pro-Pro-Gly-Phe-Ser-Pro + H2O
?
show the reaction diagram
-
-
-
-
?
Arg-Pro-Pro-Gly-Phe-Ser-Pro + H2O
?
show the reaction diagram
-
-
-
-
?
Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe + H2O
?
show the reaction diagram
-
-
-
-
?
Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg + H2O
Arg + Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg
show the reaction diagram
-
-
-
?
Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg + H2O
Arg + Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg
show the reaction diagram
-
-
-
?
Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg + H2O
Arg + Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg
show the reaction diagram
-
-
-
?
Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg + H2O
Arg + Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg
show the reaction diagram
-
-
-
?
Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg + H2O
Arg + Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg
show the reaction diagram
-
-
-
?
Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg + H2O
Arg + Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg
show the reaction diagram
-
i.e. bradykinin
-
?
Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg + H2O
Arg + Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg
show the reaction diagram
-
i.e. bradykinin
one Arg is released per mol of bradykinin in less than 5 min, the following Pro residue is released within 1 h
?
Asp-Pro-Gly-Phe-Tyr + H2O
?
show the reaction diagram
-
-
-
-
?
beta-casomorphin + H2O
?
show the reaction diagram
-
-
-
-
?
Bradykinin + H2O
?
show the reaction diagram
-
-
-
-
?
Bradykinin + H2O
?
show the reaction diagram
-
potential natural substrate, efficiently hydrolyzed by PfAPP
-
-
?
bradykinin + H2O
Arg + des-Arg-bradykinin
show the reaction diagram
-
-
-
?
bradykinin + H2O
Arg + des-Arg-bradykinin
show the reaction diagram
-
-
-
?
bradykinin + H2O
Arg + des-Arg-bradykinin
show the reaction diagram
hydrolysis of the N-terminal Arg1-Pro bond
-
?
bradykinin + H2O
Arg + des-Arg-bradykinin
show the reaction diagram
-
hydrolysis of the N-terminal Arg1-Pro2 bond
-
?
bradykinin + H2O
Arg + des-Arg-bradykinin
show the reaction diagram
-
hydrolysis of the N-terminal Arg1-Pro2 bond
-
?
bradykinin + H2O
Arg + des-Arg-bradykinin
show the reaction diagram
-
hydrolysis of the N-terminal Arg1-Pro2 bond
-
?
bradykinin + H2O
Arg + des-Arg-bradykinin
show the reaction diagram
-
i.e. RPPGFSPFR, hydrolysis of the N-terminal Arg1-Pro2 bond
i.e. PPGFSPFR
?
bradykinin + H2O
Arg + des-Arg-bradykinin
show the reaction diagram
i.e. RPPGFSPFR, hydrolysis of the N-terminal Arg1-Pro2 bond
i.e. PPGFSPFR
?
bradykinin + H2O
Arg + des-Arg-bradykinin
show the reaction diagram
-
enzyme activity in plasma of humans with previous angio-oedema, a rare but potentially life-threatening side-effect of angiotensin-converting enzyme inhibitor treatment, is low compared to humans without this sensitivity and might be a predisposing factor for development of angio-oedema
-
?
bradykinin + H2O
Arg + des-Arg-bradykinin
show the reaction diagram
-
the enzyme contributes to the degradation of bradykinin in human skin, especially in case of angiotensin-converting enzyme inhibition
-
?
bradykinin + H2O
Arg + PPGFSPFR
show the reaction diagram
i.e. RPPGFSPFR, rapid hydrolysis of the N-terminal Arg1-Pro2 bond
-
?
bradykinin + H2O
des-Arg-bradykinin + L-Arg
show the reaction diagram
-
-
-
?
bradykinin + H2O
L-Arg + des-Arg-bradykinin
show the reaction diagram
-
-
-
?
bradykinin + H2O
L-Arg + des-Arg-bradykinin
show the reaction diagram
-
-
-
?
bradykinin + H2O
L-Arg + des-Arg-bradykinin
show the reaction diagram
-
-
-
?
bradykinin + H2O
L-Arg + des-Arg-bradykinin
show the reaction diagram
-
-
-
?
centrosomal protein 290 kDa/NPHP6 + H2O
?
show the reaction diagram
-
ciliary proteome is screened for proteins with a proline in the second position: 3 candidate substrates centrosomal protein 290 kDa/NPHP6 (CEP290/NPHP6), Alstrom syndrome 1 (ALMS1), and leucine rich repeat containing 50 (LRRC50), known to cause cystic renal disease are shown to be cleaved by ecAPP
-
-
?
des-Arg9-bradykinin + H2O
?
show the reaction diagram
-
-
-
-
?
FLRF-amide + H2O
?
show the reaction diagram
-
-
-
-
?
FMRF-amide + H2O
?
show the reaction diagram
-
-
-
-
?
FPHFD + H2O
?
show the reaction diagram
-
globin pentapeptide sequence, potential natural substrate, efficiently hydrolyzed by PfAPP
-
-
?
Glu-Pro-p-nitroanilide + H2O
Glu + Pro-p-nitroanilide
show the reaction diagram
-
-
-
?
Gly-Pro + H2O
Gly + Pro
show the reaction diagram
-
-
-
?
Gly-Pro + H2O
Gly + Pro
show the reaction diagram
-
-
-
?
Gly-Pro-2-naphthylamide + H2O
Gly + Pro-2-naphthylamide
show the reaction diagram
-
-
-
?
Gly-Pro-2-naphthylamide + H2O
Gly + Pro-2-naphthylamide
show the reaction diagram
-
-
-
?
Gly-Pro-4-methylcoumarin 7-amide + H2O
Gly + Pro-4-methylcoumarin 7-amide
show the reaction diagram
-
-
-
?
Gly-Pro-4-methylcoumarin 7-amide + H2O
Gly + Pro-4-methyl-7-coumarylamide
show the reaction diagram
-
-
-
?
Gly-Pro-4-nitroanilide + H2O
Gly + Pro-4-nitroanilide
show the reaction diagram
-
-
-
?
Gly-Pro-Ala + H2O
Gly + Pro-Ala
show the reaction diagram
-
-
-
?
Gly-Pro-Ala + H2O
Gly + Pro-Ala
show the reaction diagram
-
-
-
?
Gly-Pro-Arg-Pro + H2O
?
show the reaction diagram
-
-
-
-
?
Gly-Pro-Gly-Gly + H2O
?
show the reaction diagram
-
-
-
-
?
Gly-Pro-Gly-Gly + H2O
?
show the reaction diagram
-
-
-
-
?
Gly-Pro-Gly-Gly + H2O
Gly + Pro-Gly-Gly
show the reaction diagram
-
-
-
?
Gly-Pro-hydroxyPro + H2O
Gly + Pro-hydroxyPro
show the reaction diagram
-
-
-
?
Gly-Pro-Hyp + H2O
Gly + Pro-Hyp
show the reaction diagram
-
-
-
?
Gly-Pro-Hyp + H2O
Gly + Pro-Hyp
show the reaction diagram
-
-
-
?
Gly-Pro-Hyp + H2O
Gly + Pro-Hyp
show the reaction diagram
-
-
-
?
Gly-Pro-Hyp + H2O
Gly + Pro-Hyp
show the reaction diagram
-
-
-
?
Gly-Pro-Hyp + H2O
Gly + Pro-Hyp
show the reaction diagram
-
-
-
?
Gly-Pro-Hyp + H2O
Gly + Pro-Hyp
show the reaction diagram
-
-
-
?
Gly-Pro-p-nitroanilide + H2O
Gly + Pro-p-nitroanilide
show the reaction diagram
-
-
-
?
Gly-Pro-Pro-p-nitroanilide + H2O
Gly + Pro-Pro-p-nitroanilide
show the reaction diagram
-
-
-
?
His-Pro-p-nitroanilide + H2O
His + Pro-p-nitroanilide
show the reaction diagram
-
-
-
?
K(Dnp)PPGFSPK(Abz)NH2 + H2O
?
show the reaction diagram
-
-
-
-
?
K(Dnp)PPGK(Abz)NH2 + H2O
?
show the reaction diagram
-
-
-
-
?
K(Dnp)PPK(Abz)NH2 + H2O
?
show the reaction diagram
-
-
-
-
?
KHEYLRF-amide + H2O
?
show the reaction diagram
-
-
-
-
?
KNEFIRF-amide + H2O
?
show the reaction diagram
-
-
-
-
?
KPNFLRF-amide + H2O
?
show the reaction diagram
-
-
-
-
?
KPSFVRF-amide + H2O
?
show the reaction diagram
-
-
-
-
?
KPSFVRFamide + H2O
Lys + PSFVRFamide
show the reaction diagram
-
a neuropeptide
-
?
L-Ala-L-Pro-4-nitroanilide + H2O
L-Ala + L-Pro-4-nitroanilide
show the reaction diagram
-
best substrate
-
?
L-Ala-L-Pro-4-nitroanilide + H2O
L-Ala + L-Pro-4-nitroanilide
show the reaction diagram
Streptomyces costaricanus, Streptomyces costaricanus TH-4
best substrate
-
?
L-Ala-L-Pro-L-Ala
L-Ala + L-Pro-L-Ala
show the reaction diagram
-
-
-
?
L-Ala-L-Pro-L-Ala + H2O
L-Ala + L-Pro-L-Ala
show the reaction diagram
-
-
-
?
L-Ala-L-Pro-L-Ala + H2O
L-Ala + L-Pro-L-Ala
show the reaction diagram
-
-
-
?
L-Ala-L-Pro-L-Ala-2-naphthylamide + H2O
L-Ala-L-Pro-L-Ala + 2-naphthylamine
show the reaction diagram
-
-
?
L-Ala-L-Pro-p-nitroanilide + H2O
L-Ala-L-Pro + p-nitroaniline
show the reaction diagram
-
-
?
L-Arg-L-Pro-L-Pro + H2O
L-Arg + L-Pro-L-Pro
show the reaction diagram
-
-
-
?
L-Arg-L-Pro-L-Pro + H2O
L-Arg-L-Pro + L-Pro
show the reaction diagram
-
-
-
?
L-Asn-L-Pro-L-Thr-L-Asn-L-Leu-L-His + H2O
L-Asn + L-Pro-L-Thr-L-Asn-L-Leu-L-His
show the reaction diagram
-
-
-
?
L-Ile-L-Pro-L-Pro + H2O
L-Ile + L-Pro-L-Pro
show the reaction diagram
-
-
-
?
L-Leu-L-Pro-L-Pro + H2O
L-Leu + L-Pro-L-Pro
show the reaction diagram
-
-
-
?
L-Met-L-Ala-L-Ser + H2O
L-Met + L-Ala-L-Ser
show the reaction diagram
-
-
-
?
L-Met-L-Pro + H2O
L-Met + L-Pro
show the reaction diagram
-
-
?
L-Met-L-Pro + H2O
L-Met + L-Pro
show the reaction diagram
-
-
?
L-Met-L-Pro + H2O
L-Met + L-Pro
show the reaction diagram
Thermococcus sp. NA1
-
-
?
L-Met-L-Pro + H2O
L-Met + L-Pro
show the reaction diagram
Streptomyces costaricanus TH-4
-
-
?
L-Met-L-Pro-Gly + H2O
L-Met + L-Pro-Gly
show the reaction diagram
-
-
-
?
L-Met-L-Pro-Gly + H2O
L-Met + L-Pro-Gly
show the reaction diagram
Streptomyces costaricanus, Streptomyces costaricanus TH-4
-
-
?
L-Met-L-Ser-Gly + H2O
L-Met + L-Ser-Gly
show the reaction diagram
-
-
-
?
L-Phe-L-Pro-L-Ala + H2O
L-Phe + L-Pro-L-Ala
show the reaction diagram
Streptomyces costaricanus, Streptomyces costaricanus TH-4
-
-
?
L-Phe-L-Pro-L-Gly + H2O
L-Phe + L-Pro-Gly
show the reaction diagram
Streptomyces costaricanus, Streptomyces costaricanus TH-4
-
-
?
L-prolyl-peptide + H2O
L-proline + peptide
show the reaction diagram
-
X-prolyl aminopeptidase catalyzes the removal of a penultimate prolyl residue from the N-termini of peptides
-
?
L-Val-L-Pro-L-Leu + H2O
L-Val + L-Pro-L-Leu
show the reaction diagram
-
-
-
?
L-Val-L-Pro-L-Pro + H2O
L-Val + L-Pro-L-Pro
show the reaction diagram
-
-
-
?
LemTRP-1 + H2O
Ala + PSGFLGVRamide
show the reaction diagram
-
i.e. APSGFLGVRamide
-
?
Leu-4-nitroanilide + H2O
Leu + 4-nitroanilide
show the reaction diagram
-
-
-
?
Leu-Ala-Pro + H2O
Leu + Ala-Pro
show the reaction diagram
-
-
-
?
Leu-Pro + H2O
Leu + Pro
show the reaction diagram
-
-
-
?
Leu-Pro + H2O
Leu + Pro
show the reaction diagram
-
-
-
?
Leu-Pro-Gly-Gly + H2O
Leu + Pro-Gly-Gly
show the reaction diagram
-
-
-
?
Leu-Pro-Pro + H2O
Leu + Pro-Pro
show the reaction diagram
-
-
-
?
leucine rich repeat containing 50 + H2O
?
show the reaction diagram
-
ciliary proteome is screened for proteins with a proline in the second position: 3 candidate substrates centrosomal protein 290 kDa/NPHP6 (CEP290/NPHP6), Alstrom syndrome 1 (ALMS1), and leucine rich repeat containing 50 (LRRC50), known to cause cystic renal disease are shown to be cleaved by ecAPP
-
-
?
Lys(epsilon-dinitrophenol)-Pro-Pro-NH-CH3-CH2-NH-2-aminobenzoyl + H2O
Lys(epsilon-dinitrophenol) + Pro-Pro-NH-CH3-CH2-NH-2-aminobenzoyl
show the reaction diagram
-
-
-
?
Lys-Pro-Arg + H2O
Lys + Pro-Arg
show the reaction diagram
-
-
-
?
Lys-Pro-p-nitroanilide + H2O
Lys + Pro-p-nitroanilide
show the reaction diagram
-
-
-
?
Met-Pro + H2O
Met + Pro
show the reaction diagram
-
-
-
?
N-alpha-aminobenzyloxycarbonyl-Lys-Pro-Pro-4-nitroanilide + H2O
N-alpha-aminobenzyloxycarbonyl-Lys + Pro-Pro-4-nitroaniline
show the reaction diagram
-
-
?
Nepsilon-(2-aminobenzoyl)-Lys-Pro-Pro-4-nitroanilide + H2O
?
show the reaction diagram
-
-
-
-
?
neuropeptide Y + H2O
Tyr + ?
show the reaction diagram
-
-
cleavage of the Try1-Pro2 bond
?
papain + H2O
?
show the reaction diagram
-
reduced and carboxymethylated, with the N-terminal sequence Ile-Pro-Glu-Tyr-Val
-
-
?
Phe-Pro + H2O
Phe + Pro
show the reaction diagram
-
-
-
?
Phe-Pro + H2O
Phe + Pro
show the reaction diagram
-
-
-
?
PPGFSPFR + H2O
Pro + PGFSPFR
show the reaction diagram
low activity
-
?
Pro-Pro + H2O
Pro
show the reaction diagram
-
-
-
?
Pro-Pro + H2O
Pro
show the reaction diagram
-
-
-
?
Pro-Pro + H2O
Pro
show the reaction diagram
-
-
-
?
Pro-Pro-Ala + H2O
?
show the reaction diagram
-
-
-
-
?
Pro-Pro-Gly-(Pro-Pro-Gly)4 + H2O
?
show the reaction diagram
-
-
-
-
?
RNKFEFIRF-amide + H2O
?
show the reaction diagram
-
-
-
-
?
Ser-Pro + H2O
Ser + Pro
show the reaction diagram
-
-
-
?
Ser-Pro-p-nitroanilide + H2O
Ser + Pro-p-nitroanilide
show the reaction diagram
-
-
-
?
Substance P + H2O
?
show the reaction diagram
-
-
-
-
?
substance P + H2O
Arg + des-Arg-substance P
show the reaction diagram
-
-
?
substance P + H2O
Arg + des-Arg-substance P
show the reaction diagram
i.e. RPKPQQFFGLM, hydrolysis of the N-terminal Arg1-Pro2 bond
i.e. PKPQQFFGLM
?
substance P + H2O
Arg + PKPQQFFGLM
show the reaction diagram
i.e. RPKPQQFFGLM, hydrolysis of the N-terminal Arg1-Pro2 bond
-
?
Tyr-Pro-Leu-Gly-NH2 + H2O
?
show the reaction diagram
-
-
-
-
?
Tyr-Pro-Phe + H2O
?
show the reaction diagram
-
-
-
-
?
Tyr-Pro-Phe-Pro + H2O
?
show the reaction diagram
-
-
-
-
?
Tyr-Pro-Phe-Pro-Gly + H2O
?
show the reaction diagram
-
-
-
-
-
Tyr-Pro-Phe-Pro-Gly + H2O
?
show the reaction diagram
-
-
-
-
?
Tyr-Pro-Phe-Pro-Gly-Pro-Ile + H2O
?
show the reaction diagram
-
-
-
-
-
Tyr-Pro-Phe-Pro-Gly-Pro-Ile + H2O
?
show the reaction diagram
-
-
-
-
?
Val-Pro + H2O
Val + Pro
show the reaction diagram
-
-
-
?
Val-Pro + H2O
Val + Pro
show the reaction diagram
-
-
-
?
Val-Pro + H2O
Val + Pro
show the reaction diagram
-
-
-
?
YPWTQ + H2O
?
show the reaction diagram
-
globin pentapeptide sequence, potential natural substrate, efficiently hydrolyzed by PfAPP
-
-
?
Met-Pro + H2O
Met + Pro
show the reaction diagram
-
-
-
?
additional information
?
-
-
no cleavage of human erythropoietin
-
-
-
additional information
?
-
-
the enzyme can only hydrolyze the trans form of the X-L-Pro-peptide bond, the cis form has to isomerize before it can be cleaved
-
-
-
additional information
?
-
-
the enzyme favors peptides with 2 proline residues or proline analogs in position 2 and 3 of the substrate
-
-
-
additional information
?
-
-
the enzyme liberates all unblocked preferentially basic or hydrophobic ultimate amino acids from dipeptides, tripeptides and oligopeptides with N-terminal Xaa-Pro- sequences, overview
-
-
-
additional information
?
-
-
the enzyme removes the N-terminal amino acid from peptides only where Pro, and in one case Ala, is present in the penultimate position. No hydrolysis of dipeptides even when Pro is present in the C-terminal position or when either N-termial Pro or pyroglutamate is present preceeding a Pro residue in the penultimate position of longer peptides
-
-
-
additional information
?
-
-
the enzyme releases only amino acid X from the NH2-termini of peptides with the general structure X-Pro-Y-Z
-
-
-
additional information
?
-
-
no activity with angiotensin I, des-Arg-bradykinin, AF1, i.e. KNEFIRNRVYIHPFHL, and substance P
-
-
?
additional information
?
-
no activity with Gly-Pro-hydroxyPro
-
-
?
additional information
?
-
systemin, a peptide hormone-like signaling molecule from tomato plants, is no substrate
-
-
?
additional information
?
-
-
enzyme may be important for the modulation of the biological activity of neuropeptides
-
-
-
additional information
?
-
-
the enzyme is involved in the pulmonary inactivation of circulating bradykinin
-
-
-
additional information
?
-
-
the enzyme accounts for virtually all of the pulmonary inactivation of bradykinin injected in vitro
-
-
-
additional information
?
-
-
the enzyme probably plays an important role in conjunction with other intestinal prolyl peptidases in the digestion of proline containing peptides and proteins
-
-
-
additional information
?
-
-
aminopeptidase P appears to be an important enzyme for debittering of casein-derived peptides
-
-
-
additional information
?
-
-
the enzyme is involved in degradation of peptide intermediates
-
-
-
additional information
?
-
-
the enzyme plays an important role in hydrolysis of Xaa-Pro-Yaa peptides
-
-
-
additional information
?
-
-
the enzyme may have an important role in the pulmonary degradation of the potent vasoactive peptide, bradykinin
-
-
-
additional information
?
-
-
the enzyme participates in the myocardial kinin metabolism to the same extent as angiotensin-converting enzyme, APP inhibition leads to a reduction in myocardial infarct size by the bradykinin-dependent pathway, synergistic with inhibition of angiotensin-converting enzyme, overview
-
-
?
additional information
?
-
-
enzyme hydrolyzes the Xaa-Pro peptide bond when the first amino acid is Asn, Ala, or Met
-
-
-
additional information
?
-
specific role in the catabolism of proline-containing peptides in both the vacuole and the cytosol, enzyme is required for efficient parasite proliferation
-
-
-
additional information
?
-
-
peptides in which L-Pro is replaced by N-methyl-L-Ala or L-Ala are extremely poor substrates
-
-
-
additional information
?
-
-
ciliary proteome is screened for proteins with a proline in the second position: 3 candidate substrates centrosomal protein 290 kDa/NPHP6 (CEP290/NPHP6), Alstrom syndrome 1 (ALMS1), and leucine rich repeat containing 50 (LRRC50), known to cause cystic renal disease are shown to be cleaved by ecAPP
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
Bradykinin + H2O
?
show the reaction diagram
-
potential natural substrate, efficiently hydrolyzed by PfAPP
-
-
?
bradykinin + H2O
Arg + des-Arg-bradykinin
show the reaction diagram
-
enzyme activity in plasma of humans with previous angio-oedema, a rare but potentially life-threatening side-effect of angiotensin-converting enzyme inhibitor treatment, is low compared to humans without this sensitivity and might be a predisposing factor for development of angio-oedema
-
?
bradykinin + H2O
Arg + des-Arg-bradykinin
show the reaction diagram
-
the enzyme contributes to the degradation of bradykinin in human skin, especially in case of angiotensin-converting enzyme inhibition
-
?
YPWTQ + H2O
?
show the reaction diagram
-
globin pentapeptide sequence, potential natural substrate, efficiently hydrolyzed by PfAPP
-
-
?
FPHFD + H2O
?
show the reaction diagram
-
globin pentapeptide sequence, potential natural substrate, efficiently hydrolyzed by PfAPP
-
-
?
additional information
?
-
-
enzyme may be important for the modulation of the biological activity of neuropeptides
-
-
-
additional information
?
-
-
the enzyme is involved in the pulmonary inactivation of circulating bradykinin
-
-
-
additional information
?
-
-
the enzyme accounts for virtually all of the pulmonary inactivation of bradykinin injected in vitro
-
-
-
additional information
?
-
-
the enzyme probably plays an important role in conjunction with other intestinal prolyl peptidases in the digestion of proline containing peptides and proteins
-
-
-
additional information
?
-
-
aminopeptidase P appears to be an important enzyme for debittering of casein-derived peptides
-
-
-
additional information
?
-
-
the enzyme is involved in degradation of peptide intermediates
-
-
-
additional information
?
-
-
the enzyme plays an important role in hydrolysis of Xaa-Pro-Yaa peptides
-
-
-
additional information
?
-
-
the enzyme may have an important role in the pulmonary degradation of the potent vasoactive peptide, bradykinin
-
-
-
additional information
?
-
-
the enzyme participates in the myocardial kinin metabolism to the same extent as angiotensin-converting enzyme, APP inhibition leads to a reduction in myocardial infarct size by the bradykinin-dependent pathway, synergistic with inhibition of angiotensin-converting enzyme, overview
-
-
?
additional information
?
-
Q8IKT5
specific role in the catabolism of proline-containing peptides in both the vacuole and the cytosol, enzyme is required for efficient parasite proliferation
-
-
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ca2+
-
0.5-1.0 mM, slight activation
Ca2+
activates the enzyme at concentrations of 0.01-0.1 mM with substrate substance P, inhibits above 1 mM
Ca2+
stimulation of enzyme activity at 0.4 mM, inhibition at 4 mM
Cd2+
-
activates
Co2+
-
metal ion required, Co2+ is the best activator
Co2+
-
0.03 mM, activates
Co2+
-
stimulates
Co2+
-
activates
Co2+
-
stimulates
Co2+
in a metal:protein ratio of 0.11:1, slightly activates the enzyme at 0.01-0.1 mM, 2.8fold activation at 1 mM in presence of 1 mM glutathione
Co2+
-
stimulatory at 0.01 mM, inhibitory above 0.1 mM
Co2+
activates the enzyme at concentrations of 0.01-0.1 mM with substrate substance P, inhibits above 1 mM
Co2+
stimulation of enzyme activity at 0.4 mM, inhibition at 4 mM
Co2+
or Mn2+, Zn2+, required. Maximal activity at 3 mM
Co2+
-
required
Co2+
-
10 mM, moderate inhibitory effect
Co2+
-
enhances activity
Cu2+
-
0.1 mM, moderate inhibitory effect; 10 mM, strong inhibitory effect
Cu2+
-
enhances activity
Fe2+
in a metal:protein ratio of 0.07:1
Mg2+
-
1 mM, activates
Mg2+
activates the enzyme at concentrations of 0.01-0.1 mM with substrate substance P, inhibits above 1 mM
Mg2+
stimulation of the enzyme
Mg2+
-
enhances activity
Mn2+
-
activates
Mn2+
-
0.05 mM, 3-4fold activatiion
Mn2+
-
0.005 mM, 3fold activation
Mn2+
-
required, maximal activity at 0.05 mM
Mn2+
-
0.25-1 mM activates
Mn2+
-
1 mM, 6.8fold stimulates
Mn2+
-
activates, sharp optimum at 0.37 mM
Mn2+
-
0.3-0.4 mM, 4fold stimulation with Gly-Pro-Hyp as substrate
Mn2+
-
stimulates, optimal activity at 4 mM
Mn2+
-
4-10 mM, activates hydrolysis of Gly-Pro-Hyp, beta-casomorphin or substance P
Mn2+
-
2 ions per enzyme molecule, ligand binding structure determination
Mn2+
in a metal:protein ratio of 1:1, activates the enzyme 2.80fold at 0.1 mM with substrate substance P, maximal at 0.3 mM, 4.6fold activation at 1 mM in presence of 1 mM glutathione
Mn2+
activates the enzyme at concentrations of 0.01-0.1 mM with substrate substance P, inhibits above 1 mM with substrates substance P and bradykinin
Mn2+
stimulation of the enzyme, most effective at 4 mM
Mn2+
or Co2+, Zn2+, required. Maximal activity at 20 mM
Mn2+
-
required
Mn2+
-
wild-type and mutat R404A, binding of Mn2+ with a stoichiometry of 2 per monomer
Mn2+
-
2 mol of Mn2+ ions per mol of enzyme
Mn2+
-
may substitute for Co2+
Mn2+
-
the enzyme is double Mn2+-dependent for its activity
Mn2+
-
required
Mn2+
-
enhances activity, atomic absorption studies reveal the presence of Mn2+ in the protein as a co-factor
Ni2+
-
1 mM, 26% increase in activity
Ni2+
-
may substitute for Co2+
Sn2+
-
10 mM, strong inhibitory effect
Zn2+
-
1 mM, 2fold increase in activity
Zn2+
in a metal:protein ratio of 0.11:1
Zn2+
-
mono-zinc-containing enzyme, lacks any of the typical metal binding motifs found in other zinc metalloproteases
Zn2+
or Mn2+, Co2+, required. Maximal activity at 0.4 mM
Zn2+
-
0.01 mM, moderate inhibitory effect; 10 mM, strong inhibitory effect
Mn2+
-
using the QM/MM method it is shown that XPNPEP1 employs two divalent manganese atoms (Mn(II)-Mn(II)) in the active site. The possibility of a single Mn(II) atom or other combination of divalent metal ions: Ca(II), Fe(II), Mg(II) is excluded
additional information
-
the active site contains a dinuclear metal binding site, the enzyme contains 12 metal atoms per molecule, 2 of which are Mn2+ ions
additional information
-
metalloenzyme, enzyme which is free of metals due to EDTA-treatment cannot be reactivated by addition of Co2+, Zn2+, or Mn2+
additional information
metalloprotease
additional information
-
not activating: Mg2+, Zn2+, Na+, Ca2+
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(2R,3R)-(2-hydroxy-3-amino-4-phenyl-butanoic acid)-thiazolidide
-
-
(2R,3R)-3-amino-1-oxo-4-phenyl-1-(1,3-thiazolidin-3-yl)butan-2-ol
-
-
(2R,3R)-3-amino-2-hydroxy-4-phenylbutanoyl-L-Pro
-
-
(2R,3S)-(2-hydroxy-3-amino-4-phenyl-butanoic acid)-thiazolidide
-
-
-
(2R,3S)-3-amino-1-oxo-4-phenyl-1-(1,3-thiazolidin-3-yl)butan-2-ol
-
-
(2R,3S)-3-amino-2-hydroxy-4-phenylbutanoyl-L-Pro
-
-
(2S,3R)-(2-hydroxy-3-amino-4-phenyl-butanoic acid)-Pro-methyl ester
-
-
(2S,3R)-(2-hydroxy-3-amino-4-phenyl-butanoic acid)-Pro-Phe-methyl ester
-
-
(2S,3R)-(2-hydroxy-3-amino-4-phenyl-butanoic acid)-thiazolidide
-
-
(2S,3R)-(2-hydroxy-3-amino-5-methylhexanoic acid)-thiazolidide
-
-
(2S,3R)-2-hydroxy-3-amino-4-phenyl-butanoic acid pyrrolidide
-
-
(2S,3R)-3-amino-1-oxo-4-phenyl-1-(1,3-thiazolidin-3-yl)butan-2-ol
-
-
(2S,3R)-3-amino-2-hydroxy-4-phenylbutanoyl pyrrolidide
-
-
(2S,3R)-3-amino-2-hydroxy-4-phenylbutanoyl-L-Pro
-
-
(2S,3R)-3-amino-2-hydroxy-4-phenylbutanoyl-L-Pro-L-Phe-OMe
-
-
(2S,3R)-3-amino-2-hydroxy-4-phenylbutanoyl-L-Pro-OMe
-
-
(2S,3R)-3-amino-2-hydroxy-5-methylhexanoyl-thiazolidide
-
-
(2S,3R)-3-amino-5-methyl-1-oxo-1-(1,3-thiazolidin-3-yl)hexan-2-ol
-
-
(2S,3S)-(2-hydroxy-3-amino-4-phenyl-butanoic acid)-Pro-methyl ester
-
-
(2S,3S)-3-amino-2-hydroxy-4-phenylbutanoyl-L-Pro-OMe
-
-
1,10-phenanthroline
-
-
1,10-phenanthroline
-
-
1,10-phenanthroline
-
-
1,10-phenanthroline
-
-
1,10-phenanthroline
-
-
1,10-phenanthroline
complete inhibition at 0.1 mM
1,10-phenanthroline
-
-
1,10-phenanthroline
50% inhibition at 0.036 mM
1,10-phenanthroline
-
50% inhibition at 0.01 mM
1,10-phenanthroline
-
-
1,10-phenanthroline
-
-
2-hydroxy-3-aminoacyl-Pro-OH dipeptides
-
slow-binding inhibitors
-
2-mercaptoethanol
-
-
2-mercaptoethanol
-
-
2-mercaptoethanol
-
-
2-mercaptoethanol
-
-
2-mercaptoethanol
50% inhibition at 0.043 mM
2-mercaptomethyl-3-guanidinoethylthiopropanoic acid
-
-
2-mercaptomethyl-3-guanidinoethylthiopropanoic acid
-
-
4-chloromercuriphenyl sulfonic acid
-
-
4-chloromercuriphenyl sulfonic acid
-
-
4-chloromercuriphenyl sulfonic acid
-
inhibits hydrolysis of Gly-Pro-Hyp, activates hydrolysis of bradykinin
4-chloromercuriphenyl sulfonic acid
-
inhibits cleavage of Arg-Pro-Pro
4-hydroxymercuribenzenesulfonate
-
-
4-hydroxymercuribenzoate
-
partial
4-hydroxymercuribenzoate
-
-
4-hydroxymercuribenzoate
-
-
8-hydroxyquinoline
-
-
acetyl-Phe(NO2)-Pro-Pro-HN-CH2-CH2-NH-2-aminobenzoyl
-
0.5 mM, 30% inhibition of hydrolysis of (4-nitr)Phe-Pro-Pro-HN-CH2-CH2-NH-o-aminobenzoyl
amastatin
-
-
amastatin
-
-
amastatin
-
-
antipain
-
-
Aprotinin
-
-
Aprotinin
-
slight
apstatin
-
-
apstatin
complete inhibition at 0.1 mM
apstatin
-
selective for aminopeptidase P
apstatin
-
specific inhibitor, in vivo
apstatin
-
binds to the active site with its N-terminal amino group coordinated to one of the two Mn(II) ions at the metal center
apstatin
-
50% inhibition at 0.0023 mM
bestatin
-
competitive
bestatin
-
-
bestatin
-
-
bradykinin
-
-
bradykinin
-
hydrolysis of Gly-Pro-Hyp
Ca2+
-
1 mM CaCl2, 27% inhibition
Ca2+
-
only inhibits Mn2+-activated enzyme
Ca2+
83.1% inhibition at 1 mM
Ca2+
activates the enzyme at concentrations of 0.01-0.1 mM with substrate substance P, inhibits above 1 mM
Ca2+
stimulation of enzyme activity at 0.4 mM, inhibition at 4 mM
captopril
-
-
captopril
-
-
Cd2+
-
-
CH3HgCl
-
-
cilazaprilat
-
inhibits hydrolysis of Gly-Pro-Hyp, Gly-Pro-4-methyl-7-coumarylamide, substance P, and beta-casomorphin. Weak inhibition of hydrolysis of Arg-Pro-Pro. No effect on hydrolysis of bradykinin
Co2+
-
1.5 mM CoCl2, complete inhibition
Co2+
-
1 mM CoCl2, 90% inhibition
Co2+
-
only inhibits Mn2+-activated enzyme
Co2+
inhibitory at 1 mM
Co2+
-
stimulatory at 0.01 mM, inhibitory above 0.1 mM
Co2+
activates the enzyme at concentrations of 0.01-0.1 mM with substrate substance P, inhibits above 1 mM
Co2+
stimulation of enzyme activity at 0.4 mM, inhibition at 4 mM
Cu2+
-
0.04-4.0 mM 4CuCl2
Cu2+
-
-
Cu2+
complete inhibition at 1 mM
Cu2+
56% inhibition at 0.1 mM
Cu2+
complete inhibition at 4 mM
Cu2+
-
inhibitory effect at 1 mM
diethyldicarbonate
50% inhibition at 0.011 mM
diisopropylphosphofluoridate
-
-
dithioerythritol
-
-
dithiothreitol
-
-
dithiothreitol
-
-
dithiothreitol
-
EDTA
-
reactivation by Mn2+, Co2+, Cd2+, or Ni2+
EDTA
-
0.1-1 mM, completely
EDTA
-
-
EDTA
49% inhibition at 1 mM
EDTA
80% inhibition at 0.1 mM
EDTA
50% inhibition at 0.34 m
EDTA
-
the activity of the enzyme drops to 10% after treatment with 50 mM EDTA
EGTA
-
-
enalapril
-
significant inhibition after repeated oral dosage
enalaprilat
-
inhibition only in presence of Mn2+
enaprilat
-
inhibits hydrolysis of Gly-Pro-Hyp, Gly-Pro-4-methylcoumarin 7-amide, substance P, and beta-casomorphin. Weak inhibition of hydrolysis of Arg-Pro-Pro. No effect on hydrolysis of bradykinin
-
glutathione
10% inhibition at 1 mM in absence of cations
Hg2+
-
-
iodoacetate
-
-
L-Ala-(N-methyl)L-Ala-L-Ala
-
competitive
L-Ala-L-Ala-L-Ala
-
competitive
L-Ala-L-Pro-L-Ala
-
competitive; competitive, 50% inhibition at 0.22 mM
L-Pro-L-Leu
-
product inhibition, a third metal binding site is formed by two conserved His-residues and L-Pro-L-Leu
Mg2+
38.2% inhibition at 1 mM
Mg2+
activates the enzyme at concentrations of 0.01-0.1 mM with substrate substance P, inhibits above 1 mM
Mn2+
-
0.01 M
Mn2+
-
above 4 mM
Mn2+
-
above, 0.01 mM, hydrolysis of bradykinin and Arg-Pro-Pro
N-benzyloxycarbonyl-Pro-prolinal
-
-
N-[1-(R,S)-carboxy-(2-phenylethyl)]-thiopropanoic acid
-
-
NaCl
-
2 M, complete inhibition
NaCl
-
above 0.25 M
NEM
50% inhibition at 0.079 mM
Ni2+
-
0.04-4.0 mM NiCl2
Ni2+
93.5% inhibition at 1 mM
Ni2+
complete inhibition at 0.001 mM
Ni2+
-
inhibitory effect at 1 mM
nitrilotriacetic acid
-
-
PCMB
-
partial
PCMB
-
inhibits cleavage of Arg-Pro-Pro
PCMB
-
-
pefabloc
-
-
Peptides with N-terminal Pro
-
product inhibition
phenylmethylsulfonyl fluoride
-
-
phenylmethylsulfonyl fluoride
-
-
phenylmethylsulfonyl fluoride
-
-
phosphoramidon
-
-
Pro-Gly-Pro
-
-
Pro-HN-CH2-CH2-NH-2-aminobenzoyl
-
-
Pro-HN-CH2-CH2-NH-2-aminobenzoyl
-
0.01 mM, complete inhibition of hydrolysis of (4-nitro)Phe-Pro-Pro-HN-CH2-CH2-NH-2-aminobenzoyl
Pro-HN-CH2-CH2-NH-2-aminobenzoyl
-
-
Pro-Pro-Ala
-
-
puromycin
-
-
ramiprilat
-
inhibition only in presence of Mn2+
ramiprilat
-
inhibits hydrolysis of Gly-Pro-Hyp, Gly-Pro-4-methylcoumarin 7-amide, substance P or beta-casomorphin. Weak inhibition of hydrolysis of Arg-Pro-Pro. No effect on hydrolysis of bradykinin
Zn2+
-
10 mM, complete inhibition
Zn2+
-
0.04-4.0 mM ZnCl2
Zn2+
-
1 mM ZnSO4, 96% inhibition
Zn2+
-
-
Zn2+
complete inhibition at 0.1 mM
Zn2+
complete inhibition at 0.001 mM
Zn2+
complete inhibition at 4 mM
Zn2+
-
strong
Zn2+
-
inhibitory effect at 1 mM
Mn2+
activates the enzyme at concentrations of 0.01-0.1 mM with substrate substance P, inhibits above 1 mM with substrates substance P and bradykinin
additional information
no significant inhibition by amastatin and enalaprilat
-
additional information
-
not inhibitory: bestatin, phosphoamidon
-
additional information
-
not inhibitory: L-Ala-(N-methyl)-L-Ala-L-Ala, L-Ala-L-Ala-L-Ala
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
4-chloromercuriphenyl sulfonic acid
-
inhibits hydrolysis of Gly-Pro-Hyp, activates hydrolysis of bradykinin
progesterone
-
exposure of HepG2 cells to 0.001 mM progesterone results in a significant increase in the AP-P activity of cell lysates
glutathione
activates the enzyme in presence of Mn2+ or Co2+, and slightly in presence of Zn2+
additional information
-
women on the oral contraceptive pill have higher age-adjusted plasma AP-P compared to women not on the oral contraceptive pill or males
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
3
(4-nitro)Phe-Pro-HN-CH2-CH2-NH-o-aminobenzoyl
-
-
0.22
(4-nitro)Phe-Pro-Pro-HN-CH2-CH2-NH-o-aminobenzoyl
-
-
0.087
2-aminobenzoyl-L-Lys-L-Pro-L-Pro-4-nitroanilide
-
wild-type, pH 8.1, 37C
0.14
2-aminobenzoyl-L-Lys-L-Pro-L-Pro-4-nitroanilide
-
mutant H350A, pH 8.1, 37C
0.087
Abz-L-Lys-L-Pro-L-Pro-4-nitroanilide
-
wild-type, pH 8.1, 37C
0.14
Abz-L-Lys-L-Pro-L-Pro-4-nitroanilide
-
mutant H350, pH 8.1, 37C
0.15
Arg-homoPro-Pro-Ala-NH2
-
-
-
1.23
Arg-Pro
-
-
0.16
Arg-Pro-Pro
-
-
0.35
Arg-Pro-Pro
-
without Mn2+
0.36
Arg-Pro-Pro
-
in presence of 4 mM Mn2+
0.76
Arg-Pro-Pro
-
-
0.93
Arg-Pro-Pro
-
-
1
Arg-Pro-Pro
-
-
1.4
Arg-Pro-Pro
-
-
0.0007
Arg-Pro-Pro-benzylamide
-
-
0.03
Arg-Pro-Pro-Gly
-
-
0.048
Arg-Pro-Pro-Gly-Phe
-
-
0.34
Arg-Pro-Pro-Gly-Phe
-
-
0.032
Arg-Pro-Pro-Gly-Phe-Ser
-
-
0.15
Arg-Pro-Pro-Gly-Phe-Ser
-
-
0.051
Arg-Pro-Pro-Gly-Phe-Ser-Pro
-
-
0.25
Arg-Pro-Pro-Gly-Phe-Ser-Pro
-
-
0.039
Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe
-
-
0.15
Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe
-
-
0.076
Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg
-
-
0.021
bradykinin
-
-
0.045
bradykinin
-
pH 8.0, 35C
0.047
bradykinin
-
mutant R404A, pH 7.5, 37C
0.058
bradykinin
-
37C, wild-type enzyme
0.075
bradykinin
-
pH 7.4, 37C
0.078
bradykinin
-
wild type enzyme in 100 mM Tris-HCl (pH 8.0) and 100 mM NaCl at 37C
0.101
bradykinin
pH 8.2, 37C, recombinant wild-type enzyme
0.14
bradykinin
-
pH 7.5, 37C
0.16
bradykinin
-
mutant R153W/R370L, pH 7.5, 37C
0.18
bradykinin
-
mutant R153L/R370L, pH 7.5, 37C
0.21
bradykinin
-
mutant R370L, pH 7.5, 37C
0.28
bradykinin
-
-
0.391
bradykinin
-
37C, mutant H519L
0.41
bradykinin
-
mutant R404K, pH 7.5, 37C
0.42
bradykinin
-
mutant R153A, pH 7.5, 37C
0.43
bradykinin
-
mutant R153W, pH 7.5, 37C
0.5
bradykinin
-
37C, mutant H519K
0.51
bradykinin
-
mutant R153L, pH 7.5, 37C
0.6396
bradykinin
-
pH 8, 37C
0.78
bradykinin
-
wild-type, pH 7.5, 37C
0.84
bradykinin
-
mutant Y387F, pH 7.5, 37C
0.97
bradykinin
-
pH 6.5, 37C
1.02
bradykinin
-
mutant W88L, pH 7.5, 37C
6.7
bradykinin
-
pH 5.5, 37C
0.056
des-Arg9-bradykinin
-
pH 7.4, 37C
0.51
FPHFD
-
pH 7.5, 37C
0.86
FPHFD
-
pH 5.5, 37C
0.4697
Gly-Pro-4-nitroanilide
-
pH 8, 37C
0.32
Gly-Pro-Hyp
-
without Mn2+
2
Gly-Pro-Hyp
-
in presence of 4 mM Mn2+
2.7
Gly-Pro-Hyp
-
-
40.4
Gly-Pro-Hyp
-
-
13.82
Gly-Pro-Pro-p-nitroanilide
-
-
0.018
K(Dnp)PPGFSPK(Abz)NH2
-
-
0.02
K(Dnp)PPGK(Abz)NH2
-
-
0.019
K(Dnp)PPK(Abz)NH2
-
-
0.51
L-Ala-L-Pro-4-nitroanilide
chimera th-sl cAPP, pH 7.0, 30C
0.51
L-Ala-L-Pro-4-nitroanilide
-
chimera th-sl cAPP, pH 7.0, 30C
1.4
L-Ala-L-Pro-4-nitroanilide
-
recombinant enzyme, pH 7.4, 30C
1.5
L-Ala-L-Pro-4-nitroanilide
native enzyme, pH 7.4, 30C
1.7
L-Ala-L-Pro-4-nitroanilide
recombinant enzyme, pH 7.4, 30C
16.9
L-Ala-L-Pro-4-nitroanilide
chimera sl-th cAPP, pH 8.2, 30C
16.9
L-Ala-L-Pro-4-nitroanilide
-
chimera sl-th cAPP, pH 8.2, 30C
0.77
L-Ala-L-Pro-L-Ala
-
wild-type, pH 8.1, 37C
0.308
L-Arg-L-Pro-L-Pro
-
wild type enzyme in 100 mM Tris-HCl (pH 8.0) and 100 mM NaCl at 37C
0.837
L-Arg-L-Pro-L-Pro
-
pH 7.4, 37C
2.5
L-Ile-L-Pro-L-Pro
-
pH 7, temperature not specified in the publication
-
4.7
L-Leu-L-Pro-L-Pro
-
pH 7, temperature not specified in the publication
-
0.96
L-Met-L-Pro
pH 5.0, 80C
13.6
L-Val-L-Pro-L-Pro
-
pH 7, temperature not specified in the publication
-
0.9
Leu-Pro-Pro
-
-
0.038
Lys(epsilon-dinitrophenol)-Pro-Pro-NH-CH3-CH2-NH-2-aminobenzoyl
-
-
0.077
Substance P
pH 8.2, 37C, recombinant wild-type enzyme
0.72
Tyr-Pro-Leu-Gly-NH2
-
-
1.2
Tyr-Pro-Phe
-
-
1.33
Tyr-Pro-Phe-NH2
-
-
1.02
Tyr-Pro-Phe-Pro-Gly
-
-
1.6
Tyr-Pro-Phe-Pro-Gly
-
-
0.6
Tyr-Pro-Phe-Pro-Gly-Pro-Ile
-
-
1.4
Tyr-Pro-Phe-Pro-Gly-Pro-Ile
-
-
1.4
YPWTQ
-
pH 7.5, 37C
1.8
YPWTQ
-
pH 5.5, 37C
0.1
Lys(epsilon-dinitrophenol)-Pro-Pro-NH-CH3-CH2-NH-2-aminobenzoyl
-
-
additional information
additional information
-
-
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
135
(4-nitro)Phe-Pro-HN-CH2-CH2-NH-o-aminobenzoyl
Escherichia coli
-
-
20
(4-nitro)Phe-Pro-Pro-HN-CH2-CH2-NH-o-aminobenzoyl
Escherichia coli
-
-
7.3
Abz-L-Lys-L-Pro-L-Pro-4-nitroanilide
Escherichia coli
-
mutant H350, pH 8.1, 37C
95
Abz-L-Lys-L-Pro-L-Pro-4-nitroanilide
Escherichia coli
-
wild-type, pH 8.1, 37C
73
Arg-Pro
Rattus norvegicus
-
-
49
Arg-Pro-Pro
Rattus norvegicus
-
-
120
Arg-Pro-Pro
Bos taurus
-
-
150
Arg-Pro-Pro
Rattus norvegicus
-
-
180
Arg-Pro-Pro
Rattus norvegicus
-
in presence of 4 mM Mn2+
230
Arg-Pro-Pro
Rattus norvegicus
-
without 4 mM Mn2+
125
Arg-Pro-Pro-benzylamide
Cavia porcellus
-
-
17
Arg-Pro-Pro-Gly
Rattus norvegicus
-
-
15
Arg-Pro-Pro-Gly-Phe
Rattus norvegicus
-
-
48
Arg-Pro-Pro-Gly-Phe
Bos taurus
-
-
11
Arg-Pro-Pro-Gly-Phe-Ser
Rattus norvegicus
-
-
30
Arg-Pro-Pro-Gly-Phe-Ser
Bos taurus
-
-
16
Arg-Pro-Pro-Gly-Phe-Ser-Pro
Rattus norvegicus
-
-
41
Arg-Pro-Pro-Gly-Phe-Ser-Pro
Bos taurus
-
-
13
Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe
Rattus norvegicus
-
-
39
Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe
Bos taurus
-
-
12
Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg
Rattus norvegicus
-
-
26
Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg
Bos taurus
-
-
0.17
bradykinin
Sus scrofa
-
37C, mutant H519K
0.17
bradykinin
Escherichia coli
-
mutant R404A, pH 7.5, 37C
0.24
bradykinin
Escherichia coli
-
mutant R404K, pH 7.5, 37C
1.18
bradykinin
Sus scrofa
-
37C, wild-type enzyme
1.82
bradykinin
Sus scrofa
-
37C, mutant H519L
2.94
bradykinin
Sus scrofa
-
37C, mutant H519L
3.13
bradykinin
Homo sapiens
Q9NQW7
pH 8.2, 37C, recombinant wild-type enzyme
3.8
bradykinin
Homo sapiens
-
wild type enzyme in 100 mM Tris-HCl (pH 8.0) and 100 mM NaCl at 37C
4.2
bradykinin
Escherichia coli
-
mutant Y387F, pH 7.5, 37C
4.48
bradykinin
Homo sapiens
Q9NQW7
pH 8.2, 37C, recombinant wild-type enzyme
6.08
bradykinin
Sus scrofa
-
37C, wild-type enzyme
13.8
bradykinin
Escherichia coli
-
mutant W88L, pH 7.5, 37C
16
bradykinin
Plasmodium falciparum
-
pH 7.5, 37C
38
bradykinin
Rattus norvegicus
-
-
57
bradykinin
Escherichia coli
-
mutant R153L/R370L, pH 7.5, 37C
69
bradykinin
Escherichia coli
-
wild-type, pH 7.5, 37C
70
bradykinin
Escherichia coli
-
mutant R153W, pH 7.5, 37C
72
bradykinin
Escherichia coli
-
mutant R153A, pH 7.5, 37C
87
bradykinin
Escherichia coli
-
mutant R153W/R370L, pH 7.5, 37C
88
bradykinin
Plasmodium falciparum
-
pH 6.5, 37C
102
bradykinin
Escherichia coli
-
mutant R370L, pH 7.5, 37C
109
bradykinin
Escherichia coli
-
mutant R153L, pH 7.5, 37C
160
bradykinin
Plasmodium falciparum
-
pH 5.5, 37C
5.4
FPHFD
Plasmodium falciparum
-
pH 5.5, 37C
8.6
FPHFD
Plasmodium falciparum
-
pH 7.5, 37C
48
Gly-Pro-Hyp
Rattus norvegicus
-
-
69
Gly-Pro-Hyp
Rattus norvegicus
-
in presence of 4 mM Mn2+
47.2
Gly-Pro-Pro-p-nitroanilide
Rattus norvegicus
-
-
1.5
L-Ala-L-Pro-4-nitroanilide
Streptomyces costaricanus
A9E3K0
chimera th-sl cAPP, pH 7.0, 30C
1.5
L-Ala-L-Pro-4-nitroanilide
Streptomyces lividans
-
chimera th-sl cAPP, pH 7.0, 30C
6
L-Ala-L-Pro-4-nitroanilide
Streptomyces costaricanus
A9E3K0
chimera sl-th cAPP, pH 8.2, 30C
6
L-Ala-L-Pro-4-nitroanilide
Streptomyces lividans
-
chimera sl-th cAPP, pH 8.2, 30C
45.7
L-Ala-L-Pro-4-nitroanilide
Streptomyces lividans
-
recombinant enzyme, pH 7.4, 30C
398
L-Ala-L-Pro-4-nitroanilide
Streptomyces costaricanus
A9E3K0
recombinant enzyme, pH 7.4, 30C
487
L-Ala-L-Pro-4-nitroanilide
Streptomyces costaricanus
A9E3K0
native enzyme, pH 7.4, 30C
0.77
L-Ala-L-Pro-L-Ala
Escherichia coli
-
wild-type, pH 8.1, 37C
7.7
L-Arg-L-Pro-L-Pro
Homo sapiens
-
wild type enzyme in 100 mM Tris-HCl (pH 8.0) and 100 mM NaCl at 37C
541
L-Met-L-Pro
Thermococcus sp.
Q2QC92
pH 5.0, 80C
3.1
Substance P
Homo sapiens
Q9NQW7
pH 8.2, 37C, recombinant wild-type enzyme
40
Tyr-Pro-Leu-Gly-NH2
Rattus norvegicus
-
-
58
Tyr-Pro-Phe-NH2
Rattus norvegicus
-
-
32
Tyr-Pro-Phe-Pro-Gly
Rattus norvegicus
-
-
26
Tyr-Pro-Phe-Pro-Gly-Pro-Ile
Rattus norvegicus
-
-
12
YPWTQ
Plasmodium falciparum
-
pH 5.5, 37C
150
YPWTQ
Plasmodium falciparum
-
pH 7.5, 37C
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0603
(2R,3R)-3-amino-1-oxo-4-phenyl-1-(1,3-thiazolidin-3-yl)butan-2-ol
-
pH 7.4, 30C
0.269
(2R,3R)-3-amino-1-oxo-4-phenyl-1-(1,3-thiazolidin-3-yl)butan-2-ol
-
pH 7.4, 30C
0.19
(2R,3R)-3-amino-2-hydroxy-4-phenylbutanoyl-L-Pro
-
pH 7.4, 30C
2.1
(2R,3R)-3-amino-2-hydroxy-4-phenylbutanoyl-L-Pro
-
pH 7.4, 30C
0.0282
(2R,3S)-3-amino-1-oxo-4-phenyl-1-(1,3-thiazolidin-3-yl)butan-2-ol
-
pH 7.4, 30C
0.0789
(2R,3S)-3-amino-1-oxo-4-phenyl-1-(1,3-thiazolidin-3-yl)butan-2-ol
-
pH 7.4, 30C
0.016
(2R,3S)-3-amino-2-hydroxy-4-phenylbutanoyl-L-Pro
-
pH 7.4, 30C
0.12
(2R,3S)-3-amino-2-hydroxy-4-phenylbutanoyl-L-Pro
-
pH 7.4, 30C
0.027
(2S,3R)-3-amino-1-oxo-4-phenyl-1-(1,3-thiazolidin-3-yl)butan-2-ol
-
pH 7.4, 30C
0.0307
(2S,3R)-3-amino-1-oxo-4-phenyl-1-(1,3-thiazolidin-3-yl)butan-2-ol
-
pH 7.4, 30C
0.0198
(2S,3R)-3-amino-2-hydroxy-4-phenylbutanoyl pyrrolidide
-
pH 7.4, 30C
0.037
(2S,3R)-3-amino-2-hydroxy-4-phenylbutanoyl pyrrolidide
-
pH 7.4, 30C
0.014
(2S,3R)-3-amino-2-hydroxy-4-phenylbutanoyl-L-Pro
-
pH 7.4, 30C
0.032
(2S,3R)-3-amino-2-hydroxy-4-phenylbutanoyl-L-Pro
-
pH 7.4, 30C
0.00126
(2S,3R)-3-amino-2-hydroxy-4-phenylbutanoyl-L-Pro-L-Phe-OMe
-
pH 7.4, 30C
0.057
(2S,3R)-3-amino-2-hydroxy-4-phenylbutanoyl-L-Pro-L-Phe-OMe
-
pH 7.4, 30C
0.0026
(2S,3R)-3-amino-2-hydroxy-4-phenylbutanoyl-L-Pro-OMe
-
pH 7.4, 30C
0.024
(2S,3R)-3-amino-2-hydroxy-4-phenylbutanoyl-L-Pro-OMe
-
pH 7.4, 30C
0.014
(2S,3R)-3-amino-2-hydroxy-5-methylhexanoyl-thiazolidide
-
pH 7.4, 30C
0.11
(2S,3R)-3-amino-2-hydroxy-5-methylhexanoyl-thiazolidide
-
pH 7.4, 30C
0.0043
(2S,3R)-3-amino-5-methyl-1-oxo-1-(1,3-thiazolidin-3-yl)hexan-2-ol
-
pH 7.4, 30C
0.0229
(2S,3R)-3-amino-5-methyl-1-oxo-1-(1,3-thiazolidin-3-yl)hexan-2-ol
-
pH 7.4, 30C
0.158
(2S,3S)-3-amino-2-hydroxy-4-phenylbutanoyl-L-Pro-OMe
-
pH 7.4, 30C
0.854
(2S,3S)-3-amino-2-hydroxy-4-phenylbutanoyl-L-Pro-OMe
-
pH 7.4, 30C
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.22
L-Ala-L-Pro-L-Ala
Escherichia coli
-
wild-type, pH 8.1, 37C
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.016
-
humans with previous angiotensin-converting enzyme-inhibitor treatment-associated angio-oedema
0.022 - 0.023
-
humans without angiotensin-converting enzyme-inhibitor treatment-associated angio-oedema
0.0375
-
recombinant wild-type enzyme, substrate bradykinin
0.17
-
mutant R404A, pH 7.5, 37C
0.95
-
mutant R404A, presence of guanidine, pH 7.5, 37C
3534
-
-
additional information
-
continuous spectrometric assay
additional information
-
-
additional information
-
-
additional information
-
-
additional information
-
additional information
the supernatant shows a specific activity of the recombinant enzyme of 117 units/mg, the cell-free extract shows a specific activity of the recombinant enzyme of 8 units/mg
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
5
substrate L-Met-L-Pro
6.5
-
hydrolysis of Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg
6.5 - 7
substrate Abz-L-Lys-L-Pro-L-Pro-4-nitroanilide
6.8 - 7.5
-
hydrolysis of Arg-Pro-Pro
6.9
-
native protein
7
-
hydrolysis of bradykinin(1-8), 0.5 mM, in both 0.1 M Hepes buffer or 0.1 M potassium phosphate buffer
7
-
hydrolysis of Arg-Pro-Pro
7
-
wild-type and mutant R404A
7
-
recombinant protein
7 - 8
-
with substrate bradykinin
7.5
-
assay at
7.6
with substrate substance P
7.6 - 8
-
hydrolysis of Arg-Pro-Pro, Ala-Pro or Tyr-Pro-Leu-Gly-NH2
8
-
enzyme form APP-I
8
-
6 mM imidazole buffer, Arg-Pro-Pro as substrate
8 - 8.2
-
-
8.2
recombinant enzyme expressed in Escherichia coli
9
-
enzyme form APP-II
9
-
11 mM imidazole buffer, hydrolysis of Arg-Pro-Pro
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6.5 - 10
-
about 40% of maximal activity at pH 6.5-10
7.9 - 9.5
-
about 30% of maximal activity at pH 7.9 and at pH 9.5
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
assay at
37
-
assay at
40
-
recombinant protein
41
-
enzyme form APP-II
46 - 49
-
-
55
-
enzyme form APP-I
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
40
less than 10% of maximum activity
50
less than 10% of maximum activity
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
adult fly, high level
Manually annotated by BRENDA team
-
brush border membrane
Manually annotated by BRENDA team
-
brush border membrane; small inestinal epithelial cell
Manually annotated by BRENDA team
-
expression of GFP-fusion protein
Manually annotated by BRENDA team
-
microvillar membrane
Manually annotated by BRENDA team
-
brush border membrane
Manually annotated by BRENDA team
-
expression of GFP-fusion protein
Manually annotated by BRENDA team
-
low activity in patients with angio-oedema
Manually annotated by BRENDA team
-
low activity
Manually annotated by BRENDA team
-
enriched in caveolae on the luminal surface of pulmonary vascular endothelium. Lung vascular targeting is assessed using a human/mouse chimeric monoclonal antibody (833c) against APP
Manually annotated by BRENDA team
additional information
developmentally regulated
Manually annotated by BRENDA team
additional information
enzyme is expressed through the asexual erythrocytic cycle
Manually annotated by BRENDA team
PDB
SCOP
CATH
ORGANISM
UNIPROT
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Thermotoga maritima (strain ATCC 43589 / MSB8 / DSM 3109 / JCM 10099)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
40000
-
native PAGE, SDS-PAGE
731113
41600
-
gel filtration
36047
60000
-
SDS-PAGE
731729
73000
-
SDS-PAGE, mature form
709048
90000
-
calculated from cDNA, native form
709048
125000
-
SDS-PAGE
731161
140000
approximately, gel filtration and native PAGE
649941
140000
-
X-ray crystallography
698788
143000
-
with 0.14 M NaCl, gel filtration
36057
157000
-
gel filtration
709048
200000
-
gel filtration
36040
205000
-
calculation from sedimentation and diffusion data
36050
208000
-
gel giltration
36061
210000
-
enzyme form APP-II, gel filtration
36039
217000
-
gel filtration
36044
218000
-
without NaCl, gel filtration
36057
220000
-
value depends on assay conditions, gel filtration
36054
220000
-
gel filtration
36062
220000
gel filtration
684020
230000
-
equilibrium sedimentation
36050, 36051
240000
-
native PAGE
731729
280000
-
gel filtration
36055
350000
-
enzyme form APP-I, gel filtration
36039
360000
-
gel filtration
36056
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
?
-
x * 81500 + x * 89000, SDS-PAGE
?
-
x * 90000, SDS-PAGE
?
-
non-reducing conditions, SDS-PAGE; x * 91000, reducing conditions, SDS-PAGE
?
-
x * 91000, wild-type enzyme, SDS-PAGE
?
-
x * 71000, recombinant His-tagged fusion protein, SDS-PAGE, x * 68000, W03G9.4 protein, SDS-PAGE
?
x * 71000, recombinant His-tagged enzyme, SDS-PAGE
?
x * 105000, recombinant GST-fusion protein, SDS-PAGE
?
x * 39714, calculated
?
Thermococcus sp. NA1
-
x * 39714, calculated
-
dimer
2 * 71000, recombinant enzyme, SDS-PAGE
hexamer
-
arranged in 2 types of tetramers, one tetramer comprises 4 crystallographically independent subunits, while the other tetramer comprises 2 pairs of subunits related by a crystallographic 2fold axis
homodimer
-
2 * 70000, X-ray crystallography
homodimer
-
2 * 73000, SDS-PAGE
tetramer
-
4 * 50000, SDS-PAGE
tetramer
-
x * 95000, reducing conditions, SDS-PAGE
tetramer
4 * 55000, SDS-PAGE
tetramer
-
SDS-PAGE, 4* 60000
tetramer
Streptomyces costaricanus TH-4
-
4 * 55000, SDS-PAGE
-
monomer
-
1 * 40000, SDS-PAGE
additional information
interaction of the subunits can not be disrupted by 2-mercaptoethanol, 1 M NaCl, 1% Triton X-100, and 4 mM CHAPS
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
side-chain modification
-
the enzyme is attached to the membranes via a glycosylphosphatidylinositol anchor
side-chain modification
-
glycoprotein
glycoprotein
-
secreted enzyme mutant with translational stop codon at position 658, N-glycosylated
side-chain modification
-
the enzyme is anchored to the membrane via a covalently attached glycosyl-phosphatidylinositol moiety
side-chain modification
-
the enzyme contains at least 17% N-linked carbohydrate
side-chain modification
-
the enzyme is attached to the membranes via a glycosylphosphatidylinositol anchor
glycoprotein
-
-
side-chain modification
-
-
side-chain modification
-
glycoprotein, contains up to 25% of N-linked sugar
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
8 mg/ml purified recombinant enzyme in Tris, pH 8.5, hanging drop vapour diffusion method, 0.003 ml mixed with 0.002 ml reservoir solution containing 25% PEG 4000, 0.1 M Tris-HCl, pH 8.0, 0.2 M sodium acetate, and 1 mM MnCl2, 1 month at 4C, cryoprotectant is 2-methyl-2,4-pentanediol, X-ray diffraction structure determination and analysis at 2.4 A resolution, modeling
-
in complex with inhibitor apstatin
-
Mn(II)-form of enzyme and substituted with Mg2+, Zn2+, Ca2+, Na+ and apo-enzyme in complex with L-Val-L-Pro-L-Leu
-
mutants E383A, H361A and H243A in complex with substrate L-Val-L-Pro-L-Leu. Substrate interacts with one of the active site metal ions via its terminal amino group
-
mutants H243A, D260A, D271A, H350A, H354A, H361A, E383A
-
hanging drop vapour diffusion method, using 20% (v/v) polyethylene glycol 400, 0.15 M CaCl2, and 100 mM HEPES (pH 7.5)
-
XPD43 is crystallized to 1.83 A resolution using the microbatch-under-oil technique
-
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
4.5 - 7
-
polyethylene glycol 20000 improves stability in the pH-range 4.5-7.0
36054
5 - 7.5
-
high stability at 37C
709048
5.5
-
human cytosolic APP1 is unstable and forms a high molecular weight aggregate at acidic pH
709048
7 - 10.5
-
optimal stability
36054
8
-
50C, 30 min, 50% loss of activity of enzyme form APP-I, 60C, 50% loss of activity of enzyme form APP-II
36039
8
-
50C, 30 min, 50% loss of activity
36040
8 - 11
-
37C, 2 h, maximal stability
36056
8 - 9
-
stable, enzyme form APP-II
36039
8 - 9
-
stable
36040
8.5 - 10
-
at 37C, 2 h, most stable at
36054
10
-
stable, enzyme form APP-I
36039
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0 - 37
-
reasonable stability at 0C, 20C and 37C over 15 days
731113
5 - 40
-
stable for 60 min
731161
32
stable up to
684020
37
-
pH 7.8, graduall loss of activity
36057
45
-
pH 7.8, rapid denaturation above
36057
50
-
pH 8.0, 30 min, 50% loss of activity of enzyme form APP-I
36039
50
-
pH 8.0, 30 min, 50% loss of activity
36040
50
-
enzyme retains 50% of activity after 30 min of incubation
731729
50 - 60
-
stable
36062
55
-
pH 6.8, 30 min, 0.1 M potassium phosphate buffer, stable up to
36054
60
-
pH 8.0, 30 min, 50% loss of activity of enzyme form APP-II
36039
60
-
pH 6.8, 30 min, stable up to
36056
70 - 75
-
pH 6.8, 30 min, complete loss of activity
36054
75
-
pH 6.8, 30 min, complete loss of activity
36056
80
half-life above 100 min
667265
90
half-life 90C
667265
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
loss of activity after lyophilization
-
complete loss of activity after dialysis
-
polyethylene glycol 20000 improves stability in the pH-range 4.5-7.0
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-20C, pH 6.8, stable for at least 1 month
-
4C, bicine buffer, pH 7.8, 1 mM dithiothreitol, 1 mM MnCl2, stable for several weeks
-
-20C to 4C, 0.5 mg/ml recombinant GST-fusion enzyme, several weeks without significant loss of activity
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
recombinant His-tagged enzyme from Escherichia coli
-
recombinant His-tagged enzyme from Escherichia coli
recombinant enzyme from Escherichia coli
-
Ni-NTA resin column chromatography and Hitrap Q HP affinity column chromatography
-
partial
-
recombinant His-tagged enzyme from Ecscherichia coli
using His-tag affinity chromatography and desalting
-
using a Ni2+-charged His-Trap column
-
recombinant isozyme APP2 from Escherichia coli
using Ni-NTA chromatography
-
immunoaffinity purification
-
Ni-NTA affinity chromatography
-
using Ni-NTA chromatography
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
cloning, DNA and amino acid sequence determination and analysis, and functional expression of open reading frame W03H9.4 from EST yk91g4 in Caenorhabditis elegans as GFP-fusion protein and as His-tagged enzyme in Escherichia coli
-
cloned in Escherichia coli
-
DNA and amino acid sequence determination and analysis, expression as His-tagged enzyme in Escherichia coli
overexpression in Escherichia coli
-
cloned in Escherichia coli
DNA and amino acid sequence determination and analysis, expression in Escherichia coli BL21(DE3) as His-tagged enzyme, and in COS-1 cells
expressed in Escherichia coli BL21(DE3) cells
-
expressed in Escherichia coli as a His-tagged fusion protein
-
expression as a fusion with the yellow fluorescent protein allele Citrine or with hemagglutinin tag in Plasmodium falciparum
recombinant expression in Escherichia coli as a His-tagged fusion protein
-
gene LeAPP1, DNA and amino acid sequence determination and analysis; gene LeAPP2, DNA and amino acid sequence determination and analysis, expression in Escherichia coli in N-terminal fusion with GST, a mutant form lacking 11 amino acids from the N-terminus is not active
expressed in Streptomyces lividans using the pTONA5a plasmid
expression in Escherichia coli
expressed in Escherichia coli as a His-tagged fusion protein
-
expression in Escherichia coli
-
transient expression of wild-type and mutants in COS-1 cells
-
expressed in Pichia pastoris
-
expressed in Escherichia coli as a His-tagged fusion protein
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
D260A
-
MnA is bound at the active site, but the MnB site is empty. Loss of catalytic activity; no enzymic activity
D271A
-
no atoms of Mn(II) are bound at the active site. Loss of catalytic activity; no enzymic activity
E383A
-
both Mn-(II) atoms are present in the active site, but the bridging solvent molecule is located significantly farther from the metals than in wild-type. Loss of catalytic activity; no enzymic activity
E383A
-
crystallization data. One of the two metal sites is only partially occupied
H243A
-
loss of catalytic acitivity. H243 stabilizes substrate binding; no enzymic activity
H243A
-
crystallization data. Mutant is capable of binding the substrate L-Val-L-Pro-L-Leu
H350A
-
loss of catalytic activity. H350 forms part of a hydrophobic binding pocket that gives the enzym its proline specificity; reduced enzymic activity
H354A
-
MnB is present at the active site at less than full occupancy, and a water molecule occupies the MnA site. Loss of catalytic activity; no enzymic activity
H361A
-
loss of catalytic activity; no enzymic activity
R153A
-
enzymic activity similar to wild-type
R153L
-
enzymic activity similar to wild-type
R153L/R370L
-
decrease in Km-value
R153W
-
enzymic activity similar to wild-type
R153W/R370L
-
decrease in Km-value
R370L
-
enzymic activity similar to wild-type
R404A
-
decrease both in KM- and kcat-value
R404K
-
decrease in kcat-value
W88L
-
enzymic activity similar to wild-type
Y387F
-
decrease in kcat-value
E41A
-
the mutant maintains 91% of the wild type activity and demonstrates that the acidic residue, which is considered as a stabilizing factor in the protonation of catalytic residue His498, plays only a marginal role in catalysis
D449A
-
site-directed mutagenesis, inactive mutant
D449N
-
site-directed mutagenesis, inactive mutant
D460A
-
site-directed mutagenesis, inactive mutant
D460N
-
site-directed mutagenesis, inactive mutant
E554A
-
site-directed mutagenesis, inactive mutant
E554Q
-
site-directed mutagenesis, inactive mutant
E568A
-
site-directed mutagenesis, inactive mutant
E568Q
-
site-directed mutagenesis, low expression level in COS-1 cells, inactive mutant
E588A
-
site-directed mutagenesis, 66% remaining activity compared to the wild-type enzyme with substrate bradykinin
E588Q
-
site-directed mutagenesis, 83% remaining activity compared to the wild-type enzyme with substrate bradykinin
H429K
-
site-directed mutagenesis, inactive mutant
H429L
-
site-directed mutagenesis, inactive mutant
H519K
-
site-directed mutagenesis, 2.3% remaining activity compared to the wild-type enzyme with substrate bradykinin, increased Km, reduced kcat
H519L
-
site-directed mutagenesis, 73.8% remaining activity compared to the wild-type enzyme with substrate bradykinin, increased Km
H523K
-
site-directed mutagenesis, inactive mutant
H523L
-
site-directed mutagenesis, inactive mutant
H532K
-
site-directed mutagenesis, inactive mutant
H532L
-
site-directed mutagenesis, very low expression level in COS-1 cells, protein degradation, inactive mutant
H361A
-
crystallization data. Mutant has residual catalytic activity
additional information
-
partial or complete deletion of N-terminal domain, complete loss of enzymic activity
W477E
-
the mutant, designed to block dimer formation, shows only 6% of the wild type activity
additional information
construction of chimeric enzymes th-sl cAPP, in which half of the N-terminal domain is derived from Streptomyces costaricanus and the rest is Streptomyces lividans isoform II and sl-th cAPP, in which half of the N-terminal domain is Streptomyces lividans isoform II and the rest is Streptomyces costaricanus. Both chimera are activated by Zn2+. Th-sl cAPP and slth cAPP, respectively, form a tetramer and a dimer. The pH dependence and pKa values of th-sl cAPP are almost identical to those of Streptomyces costaricanus. In contrast, sl-th cAPP shows curves and pKa values that resemble those of Streptomyces lividans isoform II
additional information
Streptomyces costaricanus TH-4
-
construction of chimeric enzymes th-sl cAPP, in which half of the N-terminal domain is derived from Streptomyces costaricanus and the rest is Streptomyces lividans isoform II and sl-th cAPP, in which half of the N-terminal domain is Streptomyces lividans isoform II and the rest is Streptomyces costaricanus. Both chimera are activated by Zn2+. Th-sl cAPP and slth cAPP, respectively, form a tetramer and a dimer. The pH dependence and pKa values of th-sl cAPP are almost identical to those of Streptomyces costaricanus. In contrast, sl-th cAPP shows curves and pKa values that resemble those of Streptomyces lividans isoform II
-
additional information
-
construction of chimeric enzymes th-sl cAPP, in which half of the N-terminal domain is derived from Streptomyces costaricanus and the rest is Streptomyces lividans isoform II and sl-th cAPP, in which half of the N-terminal domain is Streptomyces lividans isoform II and the rest is Streptomyces costaricanus. Both chimera are activated by Zn2+. Th-sl cAPP and sl-th cAPP, respectively, form a tetramer and a dimer. The pH dependence and pKa values of th-sl cAPP were almost identical to those of Streptomyces costaricanus. In contrast, sl-th cAPP showed curves and pKa values that resembled those of Streptomyces lividans isoform II
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
-
significant inhibition of enzyme after repeated oral dosage of angiotensin-converting enzyme inhibitor enalapril, but not of imidapril. Induction of dry cough by ACE inhibitors may be related to accumulation of bradykinin