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Information on EC 3.4.11.21 - aspartyl aminopeptidase and Organism(s) Homo sapiens and UniProt Accession Q9ULA0

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EC Tree
     3 Hydrolases
         3.4 Acting on peptide bonds (peptidases)
             3.4.11 Aminopeptidases
                3.4.11.21 aspartyl aminopeptidase
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This record set is specific for:
Homo sapiens
UNIPROT: Q9ULA0 not found.
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The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
Reaction Schemes
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release of an N-terminal aspartate or glutamate from a peptide, with a preference for aspartate
Synonyms
aspartyl aminopeptidase, dnpep, aspap, pfm18aap, peptidase e, acid peptidase, tgaap, m18aap, aspartyl-ap, alpha-aspartyl dipeptidase, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
acid peptidase
-
-
alpha-aspartyl dipeptidase
-
-
-
-
aminopeptidase A
-
-
-
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angiotensinase
-
-
-
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Asp-AP
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-
AspAP
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aspartate aminopeptidase
-
-
-
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aspartic aminopeptidase
-
-
-
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aspartyl aminopeptidase
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glutamyl aminopeptidase
-
-
-
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L-aspartate aminopeptidase
-
-
-
-
additional information
-
the enzyme belongs to the peptidase family M18
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
release of an N-terminal aspartate or glutamate from a peptide, with a preference for aspartate
show the reaction diagram
the conserved residues His94, His170, and His440 are essential for activity
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hydrolysis of peptide bond
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-
-
-
CAS REGISTRY NUMBER
COMMENTARY hide
9074-83-3
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SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
angiotensin + H2O
Asp + des-Asp-angiotensin
show the reaction diagram
-
intracellular protein and peptide metabolism
-
?
angiotensin II + H2O
Asp + angiotensin III
show the reaction diagram
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i.e. Asp-Tyr-Arg-Val-Tyr-Ile-His-Pro-Phe
i.e. Tyr-Arg-Val-Tyr-Ile-His-Pro-Phe
-
?
Asp-2-naphthylamide + H2O
Asp + 2-naphthylamine
show the reaction diagram
-
-
-
-
?
Asp-Ala-Pro-chromogen + H2O
Asp + Ala-Pro-chromogen
show the reaction diagram
-
-
-
-
?
Asp-Ala-Pro-sulfamethoxazole + H2O
Asp + Ala-Pro-sulfamethoxazole
show the reaction diagram
-
-
-
-
?
Asp-Lys-Ala-Leu + H2O
Asp + Lys-Ala-Leu
show the reaction diagram
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lower activity
-
-
?
N-(alpha-L-aspartyl)-4-nitroanilide + H2O
L-aspartic acid + 4-nitroaniline
show the reaction diagram
-
-
-
-
?
N-(alpha-L-glutamyl)-2-naphthylamide + H2O
L-glutamic acid + 2-naphthylamine
show the reaction diagram
-
-
-
-
?
N-(alpha-L-glutamyl)-4-nitroanilide + H2O
L-glutamic acid + 4-nitroaniline
show the reaction diagram
-
-
-
-
?
additional information
?
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substrate specificity, overview, the substrate chain length is important for activity, the enzyme has little or no activity towards aminoacyl-arylamines, no or little activity towards aspartyl dipeptides with a positively charged residue in the second position
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
angiotensin + H2O
Asp + des-Asp-angiotensin
show the reaction diagram
-
intracellular protein and peptide metabolism
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
-
the enzyme is not affected by chloride ions
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1,10-phenanthroline
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complete inhibition
DTT
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high inhibition at 1 mM
EDTA
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weak inhibition
additional information
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no inhibition by Zn2+ in contrary to glutamyl aminopeptidase, EC 3.4.11.7, no inhibition by Glu-thiol, Asp-thiol, bestatin, amastatin, and puromycin
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
2.3
Asp-Ala-Pro-sulfamethoxazole
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overexpressed enzyme
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.272 - 0.332
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overexpression in Escherichia coli
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.5
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assay at
additional information
-
neutral pH-optimum
pI VALUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.03
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sequence calculation
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
UniProt
Manually annotated by BRENDA team
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
additional information
-
broad tissue distribution
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
DNPEP_HUMAN
485
0
53410
Swiss-Prot
Mitochondrion (Reliability: 5)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
440000
-
gel filtration
52428
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8 * 55000, SDS-PAGE, 8 * 52428, amino acid sequence calculation
55000
-
8 * 55000, SDS-PAGE, 8 * 52428, amino acid sequence calculation
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
octamer
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8 * 55000, SDS-PAGE, 8 * 52428, amino acid sequence calculation
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
in complex with zinc and substrate analogue aspartate-beta-hydroxamate, to 2.2 A resolution. Structure reveals a dodecameric machinery built by domain-swapped dimers, in agreement with electron microscopy data. For both Asp-Ala and Glu-Ala substrates, the Asp and Glu side chains fit into the P1 substrate pocket without steric constraints, while the main chain is modeled onto the hydroxamate group of aspartate-beta-hydroxamate in a position optimal for hydrolysis. The P1 substrate pocket is created by strand beta15 and the beta16-alpha12 and beta17-alpha13 loops, with the beta17-lpha13 loop lining the wall and restricting the dimensions of the pocket. This limited space disfavours bulky hydrophobic residues
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
H170F
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inactive mutant enzyme
H33F
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mutant enzyme with decreased turnover number
H349F
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mutant enzyme with decreased turnover number
H352F
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dramatically reduced activity, destabilization of quarternary structure and dissociation of the native 440000 Da enzyme
H359F
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mutant enzyme with decreased turnover number
H363F
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mutant enzyme with decreased turnover number
H440F
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inactive mutant enzyme
H94F
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inactive mutant enzyme
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant His6-tagged enzyme from Escherichia coli by nickel affinity chromatography to homogeneity
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
DNA and amino acid sequence determination and analysis, expression in Escherichia coli as His6-tagged enzyme
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expression in Escherichia coli
-
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Wilk, S.; Wilk, E.; Magnusson, R.P.
Purification, characterization and cloning of a cytosolic aspartyl aminopeptidase
J. Biol. Chem.
273
15961-15970
1998
Homo sapiens, Oryctolagus cuniculus, Rattus sp.
Manually annotated by BRENDA team
Wilk, S.; Wilk, E.; Magnusson, R.P.
Identification of histidine residues important in the catalysis and structure of aspartyl aminopeptidase
Arch. Biochem. Biophys.
407
176-183
2002
Homo sapiens
Manually annotated by BRENDA team
Simmons, W.H.
Aspartyl aminopeptidase
Handbook of Proteolytic Enzymes (2nd Edition)
1
937-939
2004
Oryctolagus cuniculus, Homo sapiens, Mus musculus
-
Manually annotated by BRENDA team
Varona, A.; Blanco, L.; Lopez, J.I.; Gil, J.; Agirregoitia, E.; Irazusta, J.; Larrinaga, G.
Altered levels of acid, basic, and neutral peptidase activity and expression in human clear cell renal cell carcinoma
Am. J. Physiol. Renal Physiol.
292
F780-F788
2007
Homo sapiens
Manually annotated by BRENDA team
Banegas, I.; Barrero, F.; Duran, R.; Morales, B.; Luna, J.D.; Prieto, I.; Ramirez, M.; Alba, F.; Vives, F.
Plasma aminopeptidase activities in Parkinsons disease
Horm. Metab. Res.
38
758-760
2006
Homo sapiens
Manually annotated by BRENDA team
Chaikuad, A.; Pilka, E.; De Riso, A.; Von Delft, F.; Kavanagh, K.; Venien-Bryan, C.; Oppermann, U.; Yue, W.
Structure of human aspartyl aminopeptidase complexed with substrate analogue: Insight into catalytic mechanism, substrate specificity and M18 peptidase family
BMC Struct. Biol.
12
14
2012
Homo sapiens (Q9ULA0), Homo sapiens
Manually annotated by BRENDA team