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Information on EC 1.4.99.6 - D-arginine dehydrogenase and Organism(s) Pseudomonas aeruginosa and UniProt Accession Q9HXE3

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IUBMB Comments
Contains a non-covalent FAD cofactor. The enzyme, which has been isolated from the bacterium Pseudomonas aeruginosa PAO1, forms with EC 1.4.1.25, L-arginine dehydrogenase, a two-enzyme complex involved in the racemization of D- and L-arginine. The enzyme has a broad substrate range and can act on most D-amino acids with the exception of D-glutamate and D-aspartate. However, activity is maximal with D-arginine and D-lysine. Not active on glycine.
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This record set is specific for:
Pseudomonas aeruginosa
UNIPROT: Q9HXE3
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Word Map
The taxonomic range for the selected organisms is: Pseudomonas aeruginosa
The expected taxonomic range for this enzyme is: Bacteria, Archaea, Eukaryota
Reaction Schemes
hide(Overall reactions are displayed. Show all >>)
Synonyms
d-amino acid dehydrogenase, d-alanine dehydrogenase, d-arginine dehydrogenase, daadh, d-amino acid dehydrogenase dada, nadp+-dependent d-amino acid dehydrogenase, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
D-amino acid dehydrogenase
-
-
D-amino acid dehydrogenase DadA
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
redox reaction
-
-
-
-
oxidation
-
-
-
-
reduction
-
-
-
-
oxidative deamination
-
-
-
-
PATHWAY SOURCE
PATHWAYS
SYSTEMATIC NAME
IUBMB Comments
D-arginine:acceptor oxidoreductase (deaminating)
Contains a non-covalent FAD cofactor. The enzyme, which has been isolated from the bacterium Pseudomonas aeruginosa PAO1, forms with EC 1.4.1.25, L-arginine dehydrogenase, a two-enzyme complex involved in the racemization of D- and L-arginine. The enzyme has a broad substrate range and can act on most D-amino acids with the exception of D-glutamate and D-aspartate. However, activity is maximal with D-arginine and D-lysine. Not active on glycine.
CAS REGISTRY NUMBER
COMMENTARY hide
37205-44-0
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
D-alanine + phenazine methosulfate + H2O
pyruvate + NH3 + reduced phenazine methosulfate
show the reaction diagram
-
-
-
?
D-arginine + phenazine methosulfate
5-guanidino-2-oxopentanoate + NH3 + reduced phenazine methosulfate
show the reaction diagram
D-arginine + phenazine methosulfate + H2O
5-guanidino-2-oxopentanoate + NH3 + reduced phenazine methosulfate
show the reaction diagram
D-asparagine + phenazine methosulfate + H2O
2-oxobutanedioate + NH3 + reduced phenazine methosulfate
show the reaction diagram
-
-
-
?
D-glutamine + phenazine methosulfate + H2O
5-amino-2,5-dioxopentanoate + NH3 + reduced phenazine methosulfate
show the reaction diagram
-
-
-
?
D-histidine + phenazine methosulfate
3-(1H-imidazol-4-yl)-2-oxopropanoate + NH3 + reduced phenazine methosulfate
show the reaction diagram
D-histidine + phenazine methosulfate + H2O
3-(1H-imidazol-4-yl)-2-oxopropanoate + NH3 + reduced phenazine methosulfate
show the reaction diagram
-
-
-
?
D-isoleucine + phenazine methosulfate + H2O
3-methyl-2-oxopentanoate + NH3 + reduced phenazine methosulfate
show the reaction diagram
-
-
-
?
D-leucine + phenazine methosulfate
? + NH3 + reduced phenazine methosulfate
show the reaction diagram
D-leucine + phenazine methosulfate + H2O
4-methyl-2-oxopentanoate + NH3 + reduced phenazine methosulfate
show the reaction diagram
-
-
-
?
D-lysine + phenazine methosulfate
6-amino-2-oxohexanoate + NH3 + reduced phenazine methosulfate
show the reaction diagram
D-lysine + phenazine methosulfate + H2O
7-amino-2-oxoheptanoic acid + NH3 + reduced phenazine methosulfate
show the reaction diagram
-
-
-
?
D-methionine + phenazine methosulfate
4-methylsulfanyl-2-oxobutanoate + NH3 + reduced phenazine methosulfate
show the reaction diagram
D-methionine + phenazine methosulfate + H2O
4-methylsulfanyl-2-oxobutanoate + NH3 + reduced phenazine methosulfate
show the reaction diagram
-
-
-
?
D-phenylalanine + phenazine methosulfate
2-oxo-3-phenylpropanoate + NH3 + reduced phenazine methosulfate
show the reaction diagram
-
overall reaction
-
?
D-phenylalanine + phenazine methosulfate + H2O
2-oxo-3-phenylpropanoate + NH3 + reduced phenazine methosulfate
show the reaction diagram
-
-
-
?
D-proline + phenazine methosulfate + H2O
DELTA1-pyrroline-2-carboxylate + NH3 + reduced phenazine methosulfate
show the reaction diagram
-
-
-
?
D-serine + phenazine methosulfate + H2O
3-hydroxy-2-oxopropanoate + NH3 + reduced phenazine methosulfate
show the reaction diagram
-
-
-
?
D-threonine + phenazine methosulfate + H2O
3-hydroxy-2-oxobutanoate + NH3 + reduced phenazine methosulfate
show the reaction diagram
-
-
-
?
D-tryptophan + phenazine methosulfate + H2O
3-indole-2-oxopropanoate + NH3 + reduced phenazine methosulfate
show the reaction diagram
-
-
-
?
D-tyrosine + phenazine methosulfate
3-(4-hydroxyphenyl)-2-oxopropanoate + NH3 + reduced phenazine methosulfate
show the reaction diagram
-
overall reaction
-
?
D-tyrosine + phenazine methosulfate + H2O
(4-hydroxyphenyl)pyruvate + NH3 + reduced phenazine methosulfate
show the reaction diagram
-
-
-
?
D-valine + phenazine methosulfate + H2O
2-oxopentanoate + NH3 + reduced phenazine methosulfate
show the reaction diagram
-
-
-
?
D-alanine + H2O + FAD
pyruvate + NH3 + FADH2
show the reaction diagram
D-arginine + H2O + FAD
5-guanidino-2-oxopentanoate + NH3 + FADH2
show the reaction diagram
the enzyme is an efficient D-amino acid dehydrogenase of broad substrate specificity
-
-
?
D-arginine + H2O + iodonitrotetrazolium chloride
5-guanidino-2-oxopentanoate + NH3 + reduced iodonitrotetrazolium chloride
show the reaction diagram
-
D-arginine and D-lysine are the most effective substrates
-
-
?
D-histidine + H2O + FAD
3-(1H-imidazol-4-yl)-2-oxopropanoate + NH3 + FADH2
show the reaction diagram
the enzyme is an efficient D-amino acid dehydrogenase of broad substrate specificity
-
-
?
D-histidine + H2O + iodonitrotetrazolium chloride
3-(1H-imidazol-4-yl)-2-oxopropanoate + NH3 + reduced iodonitrotetrazolium chloride
show the reaction diagram
-
-
-
-
?
D-lysine + H2O + iodonitrotetrazolium chloride
7-amino-2-oxoheptanoic acid + NH3 + reduced iodonitrotetrazolium chloride
show the reaction diagram
-
D-arginine and D-lysine are the most effective substrates
-
-
?
D-methionine + H2O + iodonitrotetrazolium chloride
4-methylsulfanyl-2-oxobutanoate + NH3 + reduced iodonitrotetrazolium chloride
show the reaction diagram
-
-
-
-
?
D-ornithine + H2O + iodonitrotetrazolium chloride
? + NH3 + reduced iodonitrotetrazolium chloride
show the reaction diagram
-
-
-
-
?
D-phenylalanine + H2O + FAD
phenylpyruvate + NH3 + FADH2
show the reaction diagram
the enzyme is an efficient D-amino acid dehydrogenase of broad substrate specificity
-
-
?
D-phenylalanine + H2O + iodonitrotetrazolium chloride
phenylpyruvate + NH3 + reduced iodonitrotetrazolium chloride
show the reaction diagram
-
-
-
-
?
D-proline + H2O + FAD
2-oxopentanoic acid + NH3 + FADH2
show the reaction diagram
the enzyme is an efficient D-amino acid dehydrogenase of broad substrate specificity
-
-
?
D-serine + H2O + FAD
3-hydroxy-2-oxopropanoate + NH3 + FADH2
show the reaction diagram
the enzyme is an efficient D-amino acid dehydrogenase of broad substrate specificity
-
-
?
D-threonine + H2O + FAD
3-hydroxy-2-oxobutanoate + NH3 + FADH2
show the reaction diagram
the enzyme is an efficient D-amino acid dehydrogenase of broad substrate specificity
-
-
?
D-tyrosine + H2O + FAD
(4-hydroxyphenyl)pyruvate + NH3 + FADH2
show the reaction diagram
the enzyme is an efficient D-amino acid dehydrogenase of broad substrate specificity
-
-
?
D-tyrosine + H2O + iodonitrotetrazolium chloride
3-(4-hydroxyphenyl)-2-oxopropanoate + NH3 + reduced iodonitrotetrazolium chloride
show the reaction diagram
-
-
-
-
?
D-valine + H2O + FAD
2-oxopentanoate + NH3 + FADH2
show the reaction diagram
the enzyme is an efficient D-amino acid dehydrogenase of broad substrate specificity
-
-
?
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
D-alanine + H2O + FAD
pyruvate + NH3 + FADH2
show the reaction diagram
D-amino acid dehydrogenase activity of broad substrate specificity
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
D-arginine
-
substrate inhibition
D-Lysine
-
substrate inhibition
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.06 - 0.36
D-arginine
8.8 - 11
D-histidine
1.8 - 12
D-leucine
0.26
D-Lysine
10
D-methionine
11
D-phenylalanine
0.8
D-tyrosine
0.46
D-alanine
pH 8.7, 37°C
0.08 - 5.37
D-arginine
0.81 - 3.52
D-histidine
0.19
D-Lysine
-
-
1.43
D-methionine
-
-
1.48
D-ornithine
-
-
1.07 - 1.13
D-phenylalanine
1.82
D-proline
pH 8.7, 37°C
1.65
D-serine
pH 8.7, 37°C
2.47
D-threonine
pH 8.7, 37°C
0.4 - 1.78
D-tyrosine
3.01
D-valine
pH 8.7, 37°C
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1.4 - 420
D-arginine
35
D-histidine
0.061 - 55
D-leucine
141 - 550
D-Lysine
154 - 190
D-methionine
75
D-phenylalanine
23
D-tyrosine
0.74
D-alanine
pH 8.7, 37°C
1.27 - 11.1
D-arginine
0.84 - 3.6
D-histidine
9.2
D-Lysine
-
-
6.8
D-methionine
-
-
6.2
D-ornithine
-
-
1.1 - 5.3
D-phenylalanine
0.97
D-proline
pH 8.7, 37°C
0.8
D-serine
pH 8.7, 37°C
0.68
D-threonine
pH 8.7, 37°C
1.1 - 3.6
D-tyrosine
0.78
D-valine
pH 8.7, 37°C
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.041
D-alanine
pH 8.7, 25°C
0.014 - 3400
D-arginine
0.016
D-asparagine
pH 8.7, 25°C
0.186
D-glutamine
pH 8.7, 25°C
3.14 - 4
D-histidine
0.195
D-isoleucine
pH 8.7, 25°C
0.033 - 12
D-leucine
530 - 580
D-Lysine
14.8 - 36
D-methionine
6.9
D-phenylalanine
0.42
D-proline
pH 8.7, 25°C
0.0038
D-serine
pH 8.7, 25°C
0.00075
D-threonine
pH 8.7, 25°C
0.245
D-tryptophan
pH 8.7, 25°C
27.6
D-tyrosine
0.047
D-valine
pH 8.7, 25°C
1.61
D-alanine
pH 8.7, 37°C
0.236 - 150
D-arginine
1 - 1.04
D-histidine
48
D-Lysine
-
-
4.8
D-methionine
-
-
4.2
D-ornithine
-
-
1.03 - 4.7
D-phenylalanine
0.533
D-proline
pH 8.7, 37°C
0.485
D-serine
pH 8.7, 37°C
0.275
D-threonine
pH 8.7, 37°C
0.618 - 9.1
D-tyrosine
0.259
D-valine
pH 8.7, 37°C
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
24.1
D-arginine
-
-
150
D-Lysine
-
-
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
metabolism
DADH catalyzes an asynchronous CH and NH bond cleavage via a hydride transfer mechanism. The enzyme follows a ping-pong bibi mechanism. The shape and flexibility of loop L1 in the active site of DADH are important for substrate capture and broad substrate specificity
physiological function
D-to-L inversion in D-arginine metabolism requires both D-arginine dehydrogenase DauA and NAD(P)H-dependent anabolic L-arginine dehydrogenase DauB. DauA catalyzes oxidative deamination of D-arginine into 2-oxoarginine and ammonia, and DauB is able to use 2-ketoarginine and ammonia as substrates and convert them into L-arginine in the presence of NADPH or NADH. DauA and DauB are coupled catabolic and anabolic dehydrogenases that enable D-arginine utilization through L-arginine catabolic pathways
malfunction
utilization of L-Ala, L-Trp, D-Ala, D-His, D-Phe, D-Ser, D-Thr, and D-Val as sole nitrogen sources is abolished in the dadA mutant
metabolism
D-amino acid dehydrogenase activity of broad substrate specificity
physiological function
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
in complex with D-leucine, to 1.07 A resolution. Structure reveals a covalent N(5) flavin adduct, instead of the expected iminoleucine product in the active site. This acyl adduct can be reproduced by photoreduction of the enzyme in the presence of 4-methyl-2-oxopentanoic acid (ketoleucine)
in complex with iminoarginine, to 1.06 A resolution, and in complex with iminohistidine, to 1.3 A resolution. The structure comprises an unliganded conformation and a product-bound conformation. The active site is partially occupied with iminoarginine product that interacts with Tyr53 in the minor conformation of a surface loop. The guanidinium side chain of iminoarginine forms a hydrogen bond interaction with the hydroxyl of Thr50 and an ionic interaction with Glu87. In complex with iminohistidine, two alternate conformations are observed for iminohistidine where the imidazole groups form hydrogen bond interactions with the side chains of His48 and Thr50 and either Glu87 or Gln336. The different interactions and very distinct binding modes observed for iminoarginine and iminohistidine are consistent with the 1000fold difference in kcat/Km values for D-arginine and D-histidine
structure without added D-amino acids, to 1.06 A resolution, and in presence of D-arginine and D-histidine
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
A46G
mutation in loop L1. Probability of being in open conformation is higher than that of wild-type, yielding an increased level of solvent exposure of the active site. The flavin fluorescence intensity is about 2fold higher than in wild-type. Loop L1 is important for substrate capture and catalysis
E87L
kcat/Km pH-profile of the E87L mutant indicates only a single unprotonated group is required for maximal activity with D-arginine. E87 is the unprotonated group on the enzyme that binds cationic substrates
H48F
residue H48 is not responsible for the observed pKa value
S45A
mutation in loop L1. Probability of being in open conformation is higher than that of wild-type, yielding an increased level of solvent exposure of the active site. The flavin fluorescence intensity is about 2fold higher than in wild-type. Loop L1 is important for substrate capture and catalysis
Y249F
Y53F
steady-state kinetic parameters similar to those of the wild-type enzyme. Rate constants for flavin reduction (kred) with D-leucineare 3fold smaller than the wild-type value with similar pKa values for an unprotonated group of about 10.0. Cleavage of the substrate NH and CH bonds in the enzyme variant occurs in synchronous fashion, which can be reconciled with a hydride transfer mechanism
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
hexahistidine-tagged DadA
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expressed as a His-tagged fusion protein
-
expressed in Escherichia coli DH10B cells
-
overexpression in Escherichia coli
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
expression of dauBAR is specifically induced by exogenous D-arginine and D-lysine
-
highly up-regulated by L-Ala and D-Ala, followed by L-Val, L-Trp, L-Ser, L-Thr, L-Lys, Gly, L-Cys and several L-amino acids. Expression requires a transcriptional regulator, DadR
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Li, C.; Yao, X.; Lu, C.D.
Regulation of the dauBAR Operon and Characterization of D-Amino Acid Dehydrogenase DauA in Arginine and Lysine Catabolism of Pseudomonas aeruginosa PAO1
Microbiology
156
60-71
2009
Pseudomonas aeruginosa
Manually annotated by BRENDA team
Li, C.; Lu, C.D.
Arginine racemization by coupled catabolic and anabolic dehydrogenases
Proc. Natl. Acad. Sci. USA
106
906-911
2009
Pseudomonas aeruginosa (Q9HXE3)
Manually annotated by BRENDA team
Oliver, K.E.; Silo-Suh, L.
Impact of D-amino acid dehydrogenase on virulence factor production by a Pseudomonas aeruginosa
Can. J. Microbiol.
59
598-603
2013
Pseudomonas aeruginosa
Manually annotated by BRENDA team
Ball, J.; Bui, Q.V.; Gannavaram, S.; Gadda, G.
Importance of glutamate 87 and the substrate alpha-amine for the reaction catalyzed by D-arginine dehydrogenase
Arch. Biochem. Biophys.
568
56-63
2015
Pseudomonas aeruginosa (Q9HXE3)
Manually annotated by BRENDA team
Fu, G.; Yuan, H.; Li, C.; Lu, C.D.; Gadda, G.; Weber, I.T.
Conformational changes and substrate recognition in Pseudomonas aeruginosa D-arginine dehydrogenase
Biochemistry
49
8535-8545
2010
Pseudomonas aeruginosa (Q9HXE3), Pseudomonas aeruginosa
Manually annotated by BRENDA team
Yuan, H.; Fu, G.; Brooks, P.T.; Weber, I.; Gadda, G.
Steady-state kinetic mechanism and reductive half-reaction of D-arginine dehydrogenase from Pseudomonas aeruginosa
Biochemistry
49
9542-9550
2010
Pseudomonas aeruginosa (Q9HXE3), Pseudomonas aeruginosa
Manually annotated by BRENDA team
Fu, G.; Yuan, H.; Wang, S.; Gadda, G.; Weber, I.T.
Atomic-resolution structure of an N5 flavin adduct in D-arginine dehydrogenase
Biochemistry
50
6292-6294
2011
Pseudomonas aeruginosa (Q9HXE3)
Manually annotated by BRENDA team
Gannavaram, S.; Sirin, S.; Sherman, W.; Gadda, G.
Mechanistic and computational studies of the reductive half-reaction of tyrosine to phenylalanine active site variants of D-arginine dehydrogenase
Biochemistry
53
6574-6583
2014
Pseudomonas aeruginosa (Q9HXE3), Pseudomonas aeruginosa
Manually annotated by BRENDA team
Yuan, H.; Xin, Y.; Hamelberg, D.; Gadda, G.
Insights on the mechanism of amine oxidation catalyzed by D-arginine dehydrogenase through pH and kinetic isotope effects
J. Am. Chem. Soc.
133
18957-18965
2011
Pseudomonas aeruginosa (Q9HXE3)
Manually annotated by BRENDA team
Ouedraogo, D.; Souffrant, M.; Vasquez, S.; Hamelberg, D.; Gadda, G.
Importance of loop L1 dynamics for substrate capture and catalysis in Pseudomonas aeruginosa D-arginine dehydrogenase
Biochemistry
56
2477-2487
2017
Pseudomonas aeruginosa (Q9HXE3), Pseudomonas aeruginosa, Pseudomonas aeruginosa DSM 22644 (Q9HXE3)
Manually annotated by BRENDA team
He, W.; Li, C.; Lu, C.-D.
Regulation and characterization of the dadRAX locus for D-amino acid catabolism in Pseudomonas aeruginosa PAO1
J. Bacteriol.
193
2107-2115
2011
Pseudomonas aeruginosa (Q9HTQ0), Pseudomonas aeruginosa
Manually annotated by BRENDA team
Hodge-Hanson, K.M.; Downs, D.M.
Members of the Rid protein family have broad imine deaminase activity and can accelerate the Pseudomonas aeruginosa D-arginine dehydrogenase (DauA) reaction in vitro
PLoS ONE
12
e0185544
2017
Pseudomonas aeruginosa
Manually annotated by BRENDA team
Ouedraogo, D.; Ball, J.; Iyer, A.; Reis, R.A.G.; Vodovoz, M.; Gadda, G.
Amine oxidation by D-arginine dehydrogenase in Pseudomonas aeruginosa
Arch. Biochem. Biophys.
632
192-201
2017
Pseudomonas aeruginosa (Q9HXE3), Pseudomonas aeruginosa, Pseudomonas aeruginosa DSM 22644 (Q9HXE3)
Manually annotated by BRENDA team
Iyer, A.; Reis, R.A.G.; Gannavaram, S.; Momin, M.; Spring-Connell, A.M.; Orozco-Gonzalez, Y.; Agniswamy, J.; Hamelberg, D.; Weber, I.T.; Gozem, S.; Wang, S.; Germann, M.W.; Gadda, G.
A single-point mutation in D-arginine dehydrogenase unlocks a transient conformational state resulting in altered cofactor reactivity
Biochemistry
60
711-724
2021
Pseudomonas aeruginosa (Q9HXE3)
Manually annotated by BRENDA team