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Information on EC 3.5.3.18 - dimethylargininase and Organism(s) Pseudomonas aeruginosa and UniProt Accession Q9I4E3
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3.5.3.18 dimethylargininaseIUBMB Comments
Also acts on Nomega-methyl-L-arginine.
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Word Map
- 3.5.3.18
- endothelial
- cardiovascular
- artery
- hypertension
- angiotensin
- l-citrulline
- aortic
-
umbilical
-
vasodilation
- vein
-
endothelium-dependent
- dimethylamine
- atherosclerosis
- coronary
-
methylarginines
- ng,ng-dimethylarginine
- homocysteine
- medicine
- huvecs
-
endothelium-derived
- hyperhomocysteinemia
- nnos
-
l-nmma
-
ii-induced
- ng-monomethyl-l-arginine
-
monomethylarginine
-
ox-ldl
- analysis
The taxonomic range for the selected organisms is: Pseudomonas aeruginosa
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
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
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
DDAH
DDAHI
-
-
-
-
DDAHII
-
-
-
-
Dimethylargininase
-
-
-
-
dimethylarginine dimethylaminohydrolase
G6a
-
-
-
-
DDAH
-
-
-
-
dimethylarginine dimethylaminohydrolase
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of linear amidines
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
Nomega,Nomega'-dimethyl-L-arginine dimethylamidohydrolase
Also acts on Nomega-methyl-L-arginine.
CAS REGISTRY NUMBER
COMMENTARY
123644-75-7
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
NG,NG-dimethyl-L-arginine + H2O
dimethylamine + L-citrulline
-
-
-
?
Nomega-monomethyl-L-arginine + H2O
L-citrulline + methylamine
-
-
-
?
NG,NG-dimethyl-L-arginine + H2O
dimethylamine + L-citrulline
-
-
-
-
?
NG,NG-dimethyl-L-arginine + H2O
L-citrulline + dimethylamine
-
-
-
-
?
additional information
?
-
bad substrates are creatine, creatinine, argininosuccinate, guanidinoacetate, L-homoarginine, L-canvanine
-
-
?
additional information
?
-
-
bad substrates are creatine, creatinine, argininosuccinate, guanidinoacetate, L-homoarginine, L-canvanine
-
-
?
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
2-chloroacetamidine
irreversible inhibition in a time- and concentration-dependent manner
2-(N,N-dimethylamino)-diazenolate-2-oxide
-
i.e. DEANONOate, inhibition by S-nitrosylation, reversed by dithiothreitol
2-hydroxymethyl-4-chloropyridine
-
solution studies support an inactivation mechanismin in which the active site Asp66 residue stabilizes the pyridinium form of the inactivator, which has enhanced reactivity toward the active site Cys, resulting in covalent bond formation, loss of the halide, and irreversible inactivation
iodoacetamide
-
pH dependent DDAH inactivation, addition of 2.5 mM NG-methyl-L-arginine at pH 8.5 can prevent inactivation by idoacetamide, inactivation may be due to modification at the active site of DDAH, inactivation increases at higher pH values
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
physiological function
Pseudomonas aeruginosa can utilize asymmetric dimethyl-L-arginine as a sole source of nitrogen but not carbon. Expression of the DdaH gene is induced in the presence of methylarginines, including NG-monomethyl-L-arginine and asymmetric dimethyl-L-arginine. Induction of the DdaH gene is achieved via the putative enhancer-binding protein PA1196 and the alternative sigma factor RpoN. Both PA1196 and RpoN are essential for the expression of the DdaH gene in response to methylarginines
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
30500
30500
30500
calculated from the protein sequence of wild-type DDAH, after removal of the N-terminal methionine residue
30500
deconvoluted mass spectrum of a control reaction mixture that included wild-type DDAH but no inactivator
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
2 * 29000, dynamic equilibrium between monomer and homodimer, hydrodynamic measurements
homodimer
PaDDAH exists in dynamic equilibrium between symmetric homodimer and monomer states
monomer
monomer
1 * 29000, dynamic equilibrium between monomer and homodimer, hydrodynamic measurements
monomer
PaDDAH exists in dynamic equilibrium between monomer and symmetric homodimer states
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
A 2.18 A resolution X-ray crystal structure of the inactivated complex elucidates the orientation of the inactivator and its covalent attachment to the active site Cys
-
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
C249S
E33H
weakening of the homodimer interaction observed for wild type protein, expressed in Escherichia coli at levels similar to the wild type
E33Q
weakening of the homodimer interaction observed for wild type protein, expressed in Escherichia coli at levels similar to the wild type
N36D
expressed in Escherichia coli at levels similar to the wild type
N36H
weakening of the homodimer interaction observed for wild type protein, expressed in Escherichia coli at levels similar to the wild type
N36W
more stable homodimer than the wild type protein, expressed in Escherichia coli at levels similar to the wild type
Q43H
weakening of the homodimer interaction observed for wild type protein, expressed in Escherichia coli at levels similar to the wild type
Q43R
weakening of the homodimer interaction observed for wild type protein, expressed in Escherichia coli at levels similar to the wild type
R40E
weakening of the homodimer interaction observed for wild type protein, expressed in Escherichia coli at levels similar to the wild type
R40E-R98H
exclusively monomeric, expressed in Escherichia coli at levels similar to the wild type
R40W
not expressed in Escherichia coli at levels similar to the wild type
R98H
weakening of the homodimer interaction observed for wild type protein, expressed in Escherichia coli at levels similar to the wild type
R98N
not expressed in Escherichia coli at levels similar to the wild type
C249S
D244N
-
wild type and D244N DDAH variants both form covalent adducts upon incubation with 2-hydroxymethyl-4-chloropyridine, showing mass additions that are consistent with covalent attachment of one equivalent of hydroxymethylpyridine to each enzyme. These results also indicate that Asp244 is not essential for covalent modification to occur
D66N
-
the C249S mutant and D66N mutant are both incapable of forming a covalent adduct when incubated with 2-hydroxymethyl-4-chloropyridine
H162G
S248N
-
mutant is still capable of substrate turnover and is still inactivated by 2-hydroxymethyl-4-chloropyridine with a second order inactivation rate constant that is approximately 2fold less than wild type DDAH
C249S
Cys249 as the catalytic nucleophile required for intermediate formation
C249S
-
the C249S mutant and D66N mutant are both incapable of forming a covalent adduct when incubated with 2-hydroxymethyl-4-chloropyridine
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
by immobilized nickel-affinity chromatography and gel filtration
wild type to more than 98% homogeneity, by Ni-NTA affinity chromatography, mutant required additional purification step, ion-exchange chromatography followed by affinity chromatography, mutant purified to more than 95% homogeneity
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
cloned into a pET-28a expression vector, N-terminal His6-tagged protein overexpressed in Escherichia coli BL21 (DE3)
expression in Escherichia coli BL21 (DE3)
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
during growth on asymmetric dimethyl-L-arginine, induction of the DdaH gene is achieved via the putative enhancer-binding protein PA1196 and the alternative sigma factor RpoN. Both PA1196 and RpoN are essential for the expression of the DdaH gene in response to methylarginines
RENATURED/Commentary
ORGANISM
UNIPROT
LITERATURE
inhibition by 2-(N,N-dimethylamino)-diazenolate-2-oxide is reversed by dithiothreitol
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
2-chloroacetamidine may potentially find wide applicability as a general pharmacophore, useful in delineating characteristics of the amidinotransferase superfamily
additional information
additional information
dimerization is not critical for the maintenance of the biological function of the protein
additional information
-
dimerization is not critical for the maintenance of the biological function of the protein
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Santa Maria, J.; Vallance, P.; Charles, I.G.; Leiper, J.M.
Identification of microbial dimethylarginine dimethylaminohydrolase enzymes
Mol. Microbiol.
33
1278-1279
1999
Homo sapiens, Mycobacterium tuberculosis, Mus musculus, Pseudomonas aeruginosa, Rattus norvegicus, Streptomyces coelicolor
Plevin, M.J.; Magalhaes, B.S.; Harris, R.; Sankar, A.; Perkins, S.J.; Driscoll, P.C.
Characterization and manipulation of the Pseudomonas aeruginosa dimethylarginine dimethylaminohydrolase monomer--dimer equilibrium
J. Mol. Biol.
341
171-184
2004
Pseudomonas aeruginosa (Q9I4E3), Pseudomonas aeruginosa
Leiper, J.; Murray-Rust, J.; McDonald, N.; Vallance, P.
S-nitrosylation of dimethylarginine dimethylaminohydrolase regulates enzyme activity: further interactions between nitric oxide synthase and dimethylarginine dimethylaminohydrolase
Proc. Natl. Acad. Sci. USA
99
13527-13532
2002
Homo sapiens, Pseudomonas aeruginosa
Stone, E.M.; Schaller, T.H.; Bianchi, H.; Person, M.D.; Fast, W.
Inactivation of two diverse enzymes in the amidinotransferase superfamily by 2-chloroacetamidine: dimethylargininase and peptidylarginine deiminase
Biochemistry
44
13744-13752
2005
Pseudomonas aeruginosa (Q9I4E3), Pseudomonas aeruginosa
Stone, E.M.; Person, M.D.; Costello, N.J.; Fast, W.
Characterization of a transient covalent adduct formed during dimethylarginine dimethylaminohydrolase catalysis
Biochemistry
44
7069 - 7078
2005
Pseudomonas aeruginosa (Q9I4E3), Pseudomonas aeruginosa
Stone, E.M.; Costello, A.L.; Tierney, D.L.; Fast, W.
Substrate-assisted cysteine deprotonation in the mechanism of dimethylargininase (DDAH) from Pseudomonas aeruginosa
Biochemistry
45
5618-5630
2006
Pseudomonas aeruginosa
Johnson, C.M.; Linsky, T.W.; Yoon, D.W.; Person, M.D.; Fast, W.
Discovery of halopyridines as quiescent affinity labels: inactivation of dimethylarginine dimethylaminohydrolase
J. Am. Chem. Soc.
133
1553-1562
2011
Pseudomonas aeruginosa
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