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Information on EC 3.4.13.20 - beta-Ala-His dipeptidase and Organism(s) Homo sapiens and UniProt Accession Q96KN2

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     3 Hydrolases
         3.4 Acting on peptide bonds (peptidases)
             3.4.13 Dipeptidases
                3.4.13.20 beta-Ala-His dipeptidase
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Select one or more organisms in this record:
This record set is specific for:
Homo sapiens
UNIPROT: Q96KN2 not found.
Word Map
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
The taxonomic range for the selected organisms is: Homo sapiens
Reaction Schemes
preferential hydrolysis of the beta-Ala-/-His dipeptide (carnosine), and also anserine, Xaa-/-His dipeptides and other dipeptides including homocarnosine
Synonyms
carnosinase, cndp1, serum carnosinase, cndp2, carnosinase-1, cytosolic non-specific dipeptidase 2, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
carnosinase-1
247
-
CNDP1
247
-
serum carnosinase
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hydrolysis of peptide bond
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY hide
9027-21-8
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
anserine + H2O
beta-Ala + Ntau-methyl-L-histidine
show the reaction diagram
-
-
-
-
?
beta-Ala-L-His + H2O
beta-Ala + L-His
show the reaction diagram
-
-
-
?
Gly-L-His + H2O
Gly + L-His
show the reaction diagram
-
-
-
?
homocarnosine + H2O
?
show the reaction diagram
-
-
-
?
L-Ala-L-His + H2O
L-Ala + L-His
show the reaction diagram
-
-
-
?
L-carnosine + H2O
beta-Ala + His
show the reaction diagram
-
-
-
-
?
N-methylcarnosine + H2O
N-methyl-beta-Ala + L-His
show the reaction diagram
-
-
-
?
3-(acetylamino)-L-alanyl-L-histidine + H2O
3-(acetylamino)-L-alanine + L-histidine
show the reaction diagram
-
3% of the activity with carnosine
-
-
?
3-amino-L-alanyl-L-histidine + H2O
3-amino-L-alanine + L-histidine
show the reaction diagram
-
30% of the activity with carnosine
-
-
?
Ala-Ala + H2O
Ala + Ala
show the reaction diagram
-
11% of the activity with carnosine
-
-
?
Ala-His + H2O
Ala + His
show the reaction diagram
-
38% of the activity with carnosine
-
-
?
Ala-Leu + H2O
Ala + Leu
show the reaction diagram
-
13% of the activity with carnosine
-
-
?
Ala-Tyr + H2O
Ala + Tyr
show the reaction diagram
-
8% of the activity with carnosine
-
-
?
anserine + H2O
beta-Ala + Ntau-methyl-L-histidine
show the reaction diagram
beta-Ala-Ala + H2O
beta-Ala + Ala
show the reaction diagram
-
10% of the activity with carnosine
-
-
?
beta-Ala-His + H2O
beta-Ala + His
show the reaction diagram
-
i.e. carnosine
-
-
?
beta-Ala-L-His + H2O
beta-Ala + L-His
show the reaction diagram
-
i.e. L-carnosine
-
-
?
beta-Ala-Phe + H2O
beta-Ala + Phe
show the reaction diagram
-
18% of the activity with carnosine
-
-
?
carnosine + H2O
?
show the reaction diagram
-
-
-
-
?
carnosine + H2O
beta-Ala + His
show the reaction diagram
Gly-Gly + H2O
Gly + Gly
show the reaction diagram
-
7% of the activity with carnosine
-
-
?
Gly-His + H2O
Gly + His
show the reaction diagram
-
37% of the activity with carnosine
-
-
?
Gly-His-Gly + H2O
?
show the reaction diagram
-
13% of the activity with carnosine
-
-
?
Gly-His-Lys + H2O
?
show the reaction diagram
-
7% of the activity with carnosine
-
-
?
Gly-Leu + H2O
Gly + Leu
show the reaction diagram
-
21% of the activity with carnosine
-
-
?
homocarnosine + H2O
?
show the reaction diagram
Leu-Leu + H2O
Leu + Leu
show the reaction diagram
-
8% of the activity with carnosine
-
-
?
N-acetyl-3-(acetylamino)-L-alanyl-L-histidine + H2O
N-acetyl-3-(acetylamino)-L-alanine + L-histidine
show the reaction diagram
-
63% of the activity with carnosine
-
-
?
Phe-Ala + H2O
Phe + Ala
show the reaction diagram
-
8% of the activity with carnosine
-
-
?
Ser-His + H2O
Ser + His
show the reaction diagram
-
8% of the activity with carnosine
-
-
?
additional information
?
-
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
anserine + H2O
beta-Ala + Ntau-methyl-L-histidine
show the reaction diagram
-
splitting in the blood stream
-
-
?
carnosine + H2O
beta-Ala + His
show the reaction diagram
-
splitting in the blood stream
-
?
homocarnosine + H2O
?
show the reaction diagram
-
splitting of homocarnosine in the brain
-
-
?
additional information
?
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Cd2+
-
increase in kcat value
Cd2+
-
activates, twice as effective as Mn2+, maximum activity at 0.8-0.9 mM
Mn2+
-
activates, less effective than Cd2+
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
bestatin
-
-
3-(acetylamino)-L-alanyl-L-histidine
-
2.3 mM, 50% inhibition of 3-nitrotyrosine formation
3-amino-L-alanyl-L-histidine
-
3.3 mM, 50% inhibition of 3-nitrotyrosine formation
citrate
-
citrate ions are shown to bind at only three well-defined sites involving both ion pairs and hydrogen bonds. Molecular dynamics simulations evidence that citrate binding has a remarkable conformational influence on the 3D structure of carnosinase, increasing the binding affinity of carnosine to the catalytic site
EDTA
-
-
homocarnosine
-
-
N-acetyl-3-(acetylamino)-L-alanyl-L-histidine
-
2.5 mM, 50% inhibition of 3-nitrotyrosine formation
additional information
-
no inhibition by p-hydroxymercuribenzoate, CH2ClCOONa, phenylmethylsulfonyl fluoride
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
citrate
-
activates
phosphate
-
activates
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1.27 - 11
beta-Ala-L-His
0.2 - 1.9
homocarnosine
0.175 - 0.21
carnosine
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
10.6 - 138
beta-Ala-L-His
0.2 - 18
homocarnosine
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.000007
bestatin
-
pH 7.5, 30°C
0.24
homocarnosine
-
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
-
-
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.5 - 8.5
-
broad
7.4
-
assay at
8 - 8.5
-
-
8.5
-
assay at
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
37
-
assay at
30
-
assay at
37
-
assay at
pI VALUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
4.5
-
calculated
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
of adult. No expression in fetal brain
Manually annotated by BRENDA team
-
low expresion
Manually annotated by BRENDA team
-
CN1 activity is considerably higher in serum than in cerebrospinal fluid
Manually annotated by BRENDA team
additional information
-
the enzyme activity in tissues is roughly proportional to blood content for all the tissues except brain, indicating that serum carnosinase is present in the trapped blood of these tissues
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
metabolism
-
carnosine and anserine are mainly hydrolyzed by carnosinase, a low but significant amount is excreted in the urine. Carnosine reaches a steady state of very low concentration in serum, while anserine sustains higher concentrations than that of carnosine due to its greater stability vis-a-vis carnosinase after ingesting histidine-dipeptide rich diet
malfunction
-
HeLa-CN1 cells have a lower cell survival than do non-transfected cells or HeLa cells transfected with an empty or a mock vector. Viability in HeLa cells measured after H2O2 treatment is significantly higher than the viability of HeLa-CN1 cells after the same oxidant insult, indicating an increased susceptibility to oxidative stress of cells overexpressing carnosinase
physiological function
-
CN1 activity is lower in children and increases with age with no differences in protein concentration. CN1 activity is considerably higher in serum than in cerebrospinal fluid
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
Sequence
CNDP1_HUMAN
507
0
56706
Swiss-Prot
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
52800
-
2 * 82000, SDS-PAGE, 2 * 63700, MALDI-TOF, 2 * 52800, calculated
63700
-
2 * 82000, SDS-PAGE, 2 * 63700, MALDI-TOF, 2 * 52800, calculated
82000
-
2 * 82000, SDS-PAGE, 2 * 63700, MALDI-TOF, 2 * 52800, calculated
167000
-
gel filtration
65000
-
SDS-PAGE, non-reducing conditions
75000
-
2 * 75000, subunits are connected by one or more disulfide bonds, SDS-PAGE
86000
-
x* 92000, SDS-PAGE of secreted protein, x * 86000 and x * 88000, SDS-PAGE of cytosolic protein
88000
-
x* 92000, SDS-PAGE of secreted protein, x * 86000 and x * 88000, SDS-PAGE of cytosolic protein
130000
-
SDS-PAGE, reducing conditions
150000
-
SDS-PAGE, non-reducing conditions or reducing conditions
160000
-
gel filtration
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
dimer
-
2 * 82000, SDS-PAGE, 2 * 63700, MALDI-TOF, 2 * 52800, calculated
?
-
x* 92000, SDS-PAGE of secreted protein, x * 86000 and x * 88000, SDS-PAGE of cytosolic protein
dimer
-
2 * 75000, subunits are connected by one or more disulfide bonds, SDS-PAGE
monomer
-
1 * 65000, SDS-PAGE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
glycoprotein
-
after treatment with PNGase F, molecular mass shifts from 82000 Da to 62000 Da, SDS-PAGE
glycoprotein
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
D166A
-
mutation in putative metal binding site, complete loss of activity
E201A
-
mutation in putative metal binding site, complete loss of activity
E201A/D229A
-
mutation in putative metal binding site, complete loss of activity
H133A
-
mutation in putative metal binding site, complete loss of activity
additional information
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.5 - 8.2
-
maximal stability at 50°C
647115
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
37
-
up to 8 h the activity remains within 97.5% of the initial value, thereafter the activity decreases slowly
50
-
30 min, pH 7.8, stable, thermostability improved by the presence of 0.25 mM MnCl2, stability is very poor in the presence of 0.25 mM cadmium or calcium
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
inactivation during DEAE-cellulose chromatography, slow reactivation when concentrated and stored at 4°C
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-80°C, stable for several weeks in serum
-
4°C, stable for a day or two in serum
-
PURIFICATION/commentary
ORGANISM
UNIPROT
LITERATURE
recombinant enzyme
-
using DEAE Sephacel and UnoQ chromatography
-
CLONED/commentary
ORGANISM
UNIPROT
LITERATURE
expression in CHO cell
-
a stable HeLa cell line expressing recombinant human serum carnosinase CN1 is established
-
expression in COS-7 cell
-
expression in db/db mice, a model of type 2 diabetes
-
human CN1 gene is expressed in Saccharomyces cerevisiae on the yeast cell surface with alpha-agglutinin as the anchor protein
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
analysis
-
a validated method for measuring serum carnosinase activity in serum and heparin plasma
medicine
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Lenney, J.F.; George, R.P.; Weiss, A.M.; Kucera, C.M.; Chan, P.W.H.; Rinzler, G.S.
Human serum carnosinase: characterization, distinction from cellular carnosinase, and activation by cadmium
Clin. Chim. Acta
123
221-231
1982
Homo sapiens
Manually annotated by BRENDA team
Jackson, M.C.; Kucera, C.M.; Lenney, J.F.
Purification and properties of human serum carnosinase
Clin. Chim. Acta
196
193-206
1991
Homo sapiens
Manually annotated by BRENDA team
Lenney, J.F.; Peppers, S.C.; Kucera, C.M.; Ottar, S.
Homocarnosinosis: lack of serum carnosinase is the defect probably responsible for elevated brain and CSF homocarnosine
Clin. Chim. Acta
132
157-165
1983
Homo sapiens
Manually annotated by BRENDA team
Schoen, P.; Everts, H.; de Boer, T.; van Oeveren, W.
Serum carnosinase activity in plasma and serum: validation of a method and values in cardiopulmonary bypass surgery
Clin. Chem.
49
1930-1932
2003
Homo sapiens
Manually annotated by BRENDA team
Wassif, W.S.; Sherwood, R.A.; Amir, A.; Idowu, B.; Summers, B.; Leigh, N.; Peters, T.J.
Serum carnosinase activities in central nervous system disorders
Clin. Chim. Acta
225
57-64
1994
Homo sapiens
Manually annotated by BRENDA team
Cacciatore, I.; Cocco, A.; Costa, M.; Fontana, M.; Lucente, G.; Pecci, L.; Pinnen, F.
Biochemical properties of new synthetic carnosine analogues containing the residue of 2,3-diaminopropionic acid: the effect of N-acetylation
Amino Acids
28
77-83
2005
Homo sapiens
Manually annotated by BRENDA team
Zhang, H.; Chen, J.; Waldherr, C.; Hinni, K.; Waser, B.; Reubi, J.C.; Maecke, H.R.
Synthesis and evaluation of bombesin derivatives on the basis of pan-bombesin peptides labeled with indium-111, lutetium-177, and yttrium-90 for targeting bombesin receptor-expressing tumors
Cancer Res.
64
6707-6715
2004
Homo sapiens
Manually annotated by BRENDA team
Janssen, B.; Hohenadel, D.; Brinkkoetter, P.; Peters, V.; Rind, N.; Fischer, C.; Rychlik, I.; Cerna, M.; Romzova, M.; de Heer, E.; Baelde, H.; Bakker, S.J.; Zirie, M.; Rondeau, E.; Mathieson, P.; Saleem, M.A.; Meyer, J.; Koeppel, H.; Sauerhoefer, S.; Bartram, C.R.; Nawroth, P.; Hammes, H.P.; Yard, B.A.; Zschocke, J.; van der Woude, F.J.
Carnosine as a protective factor in diabetic nephropathy: association with a leucine repeat of the carnosinase gene CNDP1
Diabetes
54
2320-2327
2005
Homo sapiens
Manually annotated by BRENDA team
Bauer, K.
X-His dipeptidase
Handbook of proteolytic enzymes (Barrett, A. J. , Rawlings, N. D. , Woessner, J. F. , eds. ) Academic Press
1
1022-1024
2004
Homo sapiens, Mus musculus
-
Manually annotated by BRENDA team
Vistoli, G.; Pedretti, A.; Cattaneo, M.; Aldini, G.; Testa, B.
Homology modeling of human serum carnosinase, a potential medicinal target, and MD simulations of its allosteric activation by citrate
J. Med. Chem.
49
3269-3277
2006
Homo sapiens
Manually annotated by BRENDA team
Balion, C.M.; Benson, C.; Raina, P.S.; Papaioannou, A.; Patterson, C.; Ismaila, A.S.
Brain type carnosinase in dementia: a pilot study
BMC Neurol.
7
38
2007
Homo sapiens
Manually annotated by BRENDA team
Riedl, E.; Koeppel, H.; Brinkkoetter, P.; Sternik, P.; Steinbeisser, H.; Sauerhoefer, S.; Janssen, B.; van der Woude, F.J.; Yard, B.A.
A CTG polymorphism in the CNDP1 gene determines the secretion of serum carnosinase in Cos-7 transfected cells
Diabetes
56
2410-2413
2007
Homo sapiens
Manually annotated by BRENDA team
Sauerhoefer, S.; Yuan, G.; Braun, G.S.; Deinzer, M.; Neumaier, M.; Gretz, N.; Floege, J.; Kriz, W.; van der Woude, F.; Moeller, M.J.
L-carnosine, a substrate of carnosinase-1, influences glucose metabolism
Diabetes
56
2425-2432
2007
Homo sapiens
Manually annotated by BRENDA team
Teufel, M.; Saudek, V.; Ledig, J.P.; Bernhardt, A.; Boularand, S.; Carreau, A.; Cairns, N.J.; Carter, C.; Cowley, D.J.; Duverger, D.; Ganzhorn, A.J.; Guenet, C.; Heintzelmann, B.; Laucher, V.; Sauvage, C.; Smirnova, T.
Sequence identification and characterization of human carnosinase and a closely related non-specific dipeptidase
J. Biol. Chem.
278
6521-31
2002
Homo sapiens, Homo sapiens (Q96KN2)
Manually annotated by BRENDA team
Zschocke, J.; Nebel, A.; Wicks, K.; Peters, V.; El Mokhtari, N.E.; Krawczak, M.; van der Woude, F.; Janssen, B.; Schreiber, S.
llelic variation in the CNDP1 gene and its lack of association with longevity and coronary heart disease
Mech. Ageing Dev.
127
817-820
2006
Homo sapiens
Manually annotated by BRENDA team
Vistoli, G.; Orioli, M.; Pedretti, A.; Regazzoni, L.; Canevotti, R.; Negrisoli, G.; Carini, M.; Aldini, G.
Design, synthesis, and evaluation of carnosine derivatives as selective and efficient sequestering agents of cytotoxic reactive carbonyl species
ChemMedChem
4
967-975
2009
Homo sapiens
Manually annotated by BRENDA team
Araujo, E.C.; Suen, V.M.; Marchini, J.S.; Vannucchi, H.
Muscle mass gain observed in patients with short bowel syndrome subjected to resistance training
Nutr. Res.
28
78-82
2008
Homo sapiens
Manually annotated by BRENDA team
Peters, V.; Kebbewar, M.; Jansen, E.W.; Jakobs, C.; Riedl, E.; Koeppel, H.; Frey, D.; Adelmann, K.; Klingbeil, K.; Mack, M.; Hoffmann, G.F.; Janssen, B.; Zschocke, J.; Yard, B.A.
Relevance of allosteric conformations and homocarnosine concentration on carnosinase activity
Amino Acids
38
1607-1615
2010
Homo sapiens
Manually annotated by BRENDA team
Yeum, K.J.; Orioli, M.; Regazzoni, L.; Carini, M.; Rasmussen, H.; Russell, R.M.; Aldini, G.
Profiling histidine dipeptides in plasma and urine after ingesting beef, chicken or chicken broth in humans
Amino Acids
38
847-858
2010
Homo sapiens, Homo sapiens (Q96KN2)
Manually annotated by BRENDA team
Bellia, F.; Calabrese, V.; Guarino, F.; Cavallaro, M.; Cornelius, C.; De Pinto, V.; Rizzarelli, E.
Carnosinase levels in aging brain: redox state induction and cellular stress response
Antioxid. Redox Signal.
11
2759-2775
2009
Homo sapiens
Manually annotated by BRENDA team
Inaba, C.; Higuchi, S.; Morisaka, H.; Kuroda, K.; Ueda, M.
Synthesis of functional dipeptide carnosine from nonprotected amino acids using carnosinase-displaying yeast cells
Appl. Microbiol. Biotechnol.
86
1895-1902
2010
Homo sapiens (Q96KN2)
Manually annotated by BRENDA team
Stvolinsky, S.L.; Bulygina, E.R.; Fedorova, T.N.; Meguro, K.; Sato, T.; Tyulina, O.V.; Abe, H.; Boldyrev, A.A.
Biological activity of novel synthetic derivatives of carnosine
Cell. Mol. Neurobiol.
30
395-404
2010
Homo sapiens
Manually annotated by BRENDA team
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