We're sorry, but BRENDA doesn't work properly without JavaScript. Please make sure you have JavaScript enabled in your browser settings.
Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
EC Tree
The taxonomic range for the selected organisms is: Bos taurus The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
Synonyms
ddah1, dimethylarginine dimethylaminohydrolase, ddah2, ddah-1, ddah-2, dimethylaminohydrolase, dimethylarginine dimethylaminohydrolase 1, dimethylargininase, human ddah-1, ddah-i,
more
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
dimethylarginine dimethylaminohydrolase
-
Nomega,Nomega-dimethyl-L-arginine dimethylaminohydrolase-1
-
Dimethylargininase
-
-
-
-
dimethylarginine dimethylaminohydrolase
dimethylarginine dimethylaminohydrolase 1
-
-
dimethylarginine dimethylaminohydrolase
-
-
-
-
dimethylarginine dimethylaminohydrolase
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
hydrolysis of linear amidines
-
-
-
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Nomega,Nomega'-dimethyl-L-arginine dimethylamidohydrolase
Also acts on Nomega-methyl-L-arginine.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
dimethyl-L-arginine + H2O
L-citrulline + dimethylamine
-
-
-
?
N,N-dimethyl-L-arginine + H2O
dimethylamine + L-citrulline
-
-
-
?
NG,NG-dimethyl-L-arginine + H2O
dimethylamine + L-citrulline
NG-monomethyl-L-arginine + H2O
citrulline + methylamine
-
-
-
-
?
Ngamma-monomethyl-L-arginine + H2O
L-citrulline + methylamine
-
-
-
?
S-methyl-L-thiocitrulline + H2O
L-citrulline + methanethiol
-
-
-
?
NG,NG-dimethyl-L-arginine + H2O
dimethylamine + L-citrulline
-
-
-
-
?
NG,NG-dimethyl-L-arginine + H2O
dimethylamine + L-citrulline
-
enzyme is involved in regulation of the levels of the natural occuring free arginine derivatives L-Nomega,Nomega-dimethylarginine and L-Nomega-methylarginine, which are reversible inhibitors of nitric oxide synthase
-
-
?
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
NG,NG-dimethyl-L-arginine + H2O
dimethylamine + L-citrulline
-
enzyme is involved in regulation of the levels of the natural occuring free arginine derivatives L-Nomega,Nomega-dimethylarginine and L-Nomega-methylarginine, which are reversible inhibitors of nitric oxide synthase
-
-
?
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Zn2+
Zn2+ binding to DDAH-1 protects the enzyme from S-nitrosylation by free nitric oxide
Zn2+
-
contains one tightly bound zinc ion
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
S-nitroso-L-cysteine
9-15% inhibition of the zinc-free enzyme at 0.5 mM, S-nitrosylation of the active site Cys273 in DDAH-1
2-(N,N-dimethylamino)-diazenolate-2-oxide
-
S-nitrosylation of apo-enzyme, holo-enzyme resists, reaction with two of five Cys-residues
methylamine
-
10 mM, 80% of activity
N-nitro-L-arginine methylester
additional information
5 mM of L-cysteine, L-homocysteine, glutathione, dithiothreitol, or Tris(2-carboxyethyl)phosphine-HCl for 30 min at 37°C cannot restore inhibited activity, suggesting that the covalent product N-thiosulfoximide will remain stable under the reducing conditions present in the cytosol
-
S-nitroso-L-homocysteine
-
S-nitroso-L-homocysteine
96% inhibition of the zinc-free enzyme at 0.5 mM, leads to the unique formation of an N-thiosulfoximide
N-nitro-L-arginine methylester
1 mM, 1 h, 47.1% relative activity
N-nitro-L-arginine methylester
1mM, 1 h, 47.1% relative activity
Zn2+
-
besides the tightly bound zinc, additional Zn2+ inhibit competitively
Zn2+
-
endogenous inhibitor, regulatory role
Zn2+
-
one mol per mol of enzyme, apo-enzyme is active, holoenzyme is activated by removal of Zn2+
Zn2+
20 microM, 40% relative activity
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
D-histidine
-
activating ability in decreasing order: histamine, imidazole, L-histidine, D-histidine
histamine
-
activating ability in decreasing order: histamine, imidazole, L-histidine, D-histidine
imidazole
-
activating ability in decreasing order: histamine, imidazole, L-histidine, D-histidine
L-histidine
-
activating ability in decreasing order: histamine, imidazole, L-histidine, D-histidine
additional information
-
type of buffer dramatically influences enzyme activity, activity in imidazole/HCl buffer is about 25% higher than in phosphate buffer
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
0.18
dimethyl-L-arginine
-
1.31
NG,NG-dimethyl-L-arginine
-
-
1.6
NG-monomethyl-L-arginine
-
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
0.27
NG,NG-dimethyl-L-arginine
-
-
0.34
NG-monomethyl-L-arginine
-
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
0.69
S-nitroso-L-homocysteine
in the presence of 5 mM EDTA, at pH 7.3 and 37°C
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
0.075
S-nitroso-L-homocysteine
Bos taurus
in 50 mM HEPES/NaOH (pH 7.3), 150 mM KCl, and 5 mM EDTA for 30 min at 37°C
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
6.8
-
imidazole/HCl buffer
additional information
-
type of buffer dramatically influences enzymatic activity
6.2
-
phosphate buffer
6.2
-
hydrolysis of NG,NG-dimethyl-L-arginine
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
-
UniProt
brenda
isoform DDAH-1
UniProt
brenda
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
-
brenda
aortic endothelial cell
brenda
-
brenda
-
-
brenda
aortic endothelial cell
brenda
-
brenda
-
brenda
-
brenda
-
brenda
-
brenda
-
-
brenda
-
brenda
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
physiological function
overexpression of DDAH-1 increases endothelial nitric oxide by 24%. Small interfering RNA-mediated down-regulation of DDAH-1 reduces nitric oxide bioavailability by 27%. The reduction in nitric oxide production following DDAH-1 gene silencing is associated with a 48% reduction in L-Arg/asymmetric dimethylarginine and is partially restored with L-Arg supplementation
physiological function
overexpression of DDAH-2 increases endothelial nitric oxide by 18%. Small interfering RNA-mediated down-regulation of DDAH-2 reduces nitric oxide bioavailability by 57%. L-Arg and asymmetric dimethylarginine are unchanged in the DDAH-2-silenced cells, and L-Arg supplementation has no effect on nitric oxide
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
DDAH1_BOVIN
285
0
31289
Swiss-Prot
Mitochondrion (Reliability: 2 )
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
31200
electrospray ionization mass spectrometry
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
by sitting drop vapor diffusion, at 1.08-2.0 A resolution and at pH 6.3 and pH 9.0
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
50
-
2 h, holo-enzyme retains ca. 56% of the original activity, no residual activity of the apoenzyme. Thermal denaturation of both protein forms is irreversible
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Zn2+ has a structure-stabilizing role
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
anion exchange chromatography and gel filtration chromatography
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
method for reversible preparation of metal-free and metal-containing enzyme
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
medicine
structure-based development of specific DDAH-1 inhibitors that might be useful in the therapeutic treatment of NOS dysfunction-related diseases
medicine
-
expression and secretion of the vascular endothelial growth factor is not increased in DDAH1-transfected cells
medicine
influence on atherosclerosis in experimental models by increased ADMA concentrations and reduced NO synthesis
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Bogumil, R.; Knipp, M.; Fundel, S.M.; Vasak, M.
Characterization of dimethylargininase from bovine brain: evidence for a zinc binding site
Biochemistry
37
4791-4798
1998
Bos taurus
brenda
Knipp, M.; Charnock, J.M.; Garner, C.D.; Vasak, M.
Structural and functional characterization of the Zn(II) site in dimethylargininase-1 (DDAH-1) from bovine brain. Zn(II) release activates DDAH-1
J. Biol. Chem.
276
40449-40456
2001
Bos taurus
brenda
Knipp, M.; Braun, O.; Gehrig, P.M.; Sack, R.; Vasak, M.
Zn(II)-free dimethylargininase-1 (DDAH-1) is inhibited upon specific Cys-S-nitrosylation
J. Biol. Chem.
278
3410-3416
2003
Bos taurus
brenda
Hasegawa, K.; Wakino, S.; Tanaka, T.; Kimoto, M.; Tatematsu, S.; Kanda, T.; Yoshioka, K.; Homma, K.; Sugano, N.; Kurabayashi, M.; Saruta, T.; Hayashi, K.
Dimethylarginine dimethylaminohydrolase 2 increases vascular endothelial growth factor expression through Sp1 transcription factor in endothelial cells
Arterioscler. Thromb. Vasc. Biol.
26
1488-1494
2006
Bos taurus, Homo sapiens
brenda
Frey, D.; Braun, O.; Briand, C.; Vak, M.; Grtter, M.G.
Structure of the mammalian NOS regulator dimethylarginine dimethylaminohydrolase: a basis for the design of specific inhibitors
Structure
14
901-911
2006
Bos taurus (P56965), Bos taurus
brenda
Braun, O.; Knipp, M.; Chesnov, S.; Vasak, M.
Specific reactions of S-nitrosothiols with cysteine hydrolases: A comparative study between dimethylargininase-1 and CTP synthetase
Protein Sci.
16
1522-1534
2007
Bos taurus (P56965)
brenda
Wadham, C.; Mangoni, A.A.
Dimethylarginine dimethylaminohydrolase regulation: a novel therapeutic target in cardiovascular disease
Expert. Opin. Drug Metab. Toxicol.
5
303-319
2009
Bos taurus, Bos taurus (Q3SX44), Oryctolagus cuniculus, Rattus norvegicus (O08557), Rattus norvegicus (Q6MG60), Homo sapiens (O94760), Homo sapiens (O95865), Mus musculus (Q99LD8), Mus musculus (Q9CWS0)
brenda
Pope, A.J.; Karrupiah, K.; Kearns, P.N.; Xia, Y.; Cardounel, A.J.
Role of dimethylarginine dimethylaminohydrolases in the regulation of endothelial nitric oxide production
J. Biol. Chem.
284
35338-35347
2009
Bos taurus (P56965), Bos taurus (Q3SX44)
brenda