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Information on EC 2.6.99.3 - O-ureido-L-serine synthase and Organism(s) Streptomyces lavendulae and UniProt Accession D2Z027

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IUBMB Comments
The enzyme participates in the biosynthetic pathway of D-cycloserine, an antibiotic substance produced by several Streptomyces species. Also catalyses EC 2.5.1.47, cysteine synthase.
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Streptomyces lavendulae
UNIPROT: D2Z027
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The taxonomic range for the selected organisms is: Streptomyces lavendulae
The enzyme appears in selected viruses and cellular organisms
Synonyms
DcsD, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SYSTEMATIC NAME
IUBMB Comments
O-acetyl-L-serine:hydroxyurea 2-amino-2-carboxyethyltransferase
The enzyme participates in the biosynthetic pathway of D-cycloserine, an antibiotic substance produced by several Streptomyces species. Also catalyses EC 2.5.1.47, cysteine synthase.
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
O-acetyl-L-serine + hydroxyurea
O-ureido-L-serine + acetate
show the reaction diagram
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
O-acetyl-L-serine + hydroxyurea
O-ureido-L-serine + acetate
show the reaction diagram
the enzyme participates in the biosynthetic pathway of D-cycloserine, an antibiotic substance produced by several Streptomyces species
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
pyridoxal 5'-phosphate
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
9 - 18
Hydroxyurea
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
4.6 - 11
Hydroxyurea
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.002 - 1.2
Hydroxyurea
0.15
O-acetyl-L-serine
30°C, pH 8.0, cosubstrate: hydroxyurea
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
9
activity increases from pH 5.0 to pH 9.0
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.5 - 9
activity at pH 7.5 is about 45% compared to activity at pH 9.0
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
DCSD_STRLA
324
0
34592
Swiss-Prot
-
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
126000
gel filtration
36000
4 * 36000, SDS-PAGE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
tetramer
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
wild-type and mutant K43A, to 2.25 and 1.9 A resolution, respectively. Each monomer of DcsD takes a typical fold of type II pyridoxal 5'-phosphate enzymes with the cofactor pyridoxal 5'-phosphate covalently bound to invariant Lys residue (Lys43) at the active site. The pyridine ring of pyridoxal 5'-phoshate makes hydrogen bonds with invariant Asn73 and Ser265 residues. Its phosphate group makes hydrogen bonds with Gly177, Thr178, Thr179 and Thr181 residues
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
K43A
mutation in invariant Lys43 residue, inactive. Mutant forms an external aldimine adduct upon addition of L-methionine or O-ureido-L-serine
S121A
decreased activity for synthesis of ureido-L-serine, increased activity for synthesis of L-cysteine
S121M
decreased activity for synthesis of ureido-L-serine, increased activity for synthesis of L-cysteine
V74T
decreased activity for synthesis of ureido-L-serine, increased activity for synthesis of L-cysteine
Y97F
decreased activity for synthesis of ureido-L-serine, increased activity for synthesis of L-cysteine
Y97M
decreased activity for synthesis of ureido-L-serine, increased activity for synthesis of L-cysteine
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression in Escherichia coli
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
synthesis
expression of a D-cycloserine biosynthetic gene cluster consisting of 10 open reading frames (dcsA to dcsJ) from Streptomyces lavendulae ATCC 11924 in Escherichia coli. When L-serine and hydroxyurea, the precursors of D-cycloserine, are incubated together with the Escherichia coli resting cell suspension, the cells produce significant amounts of D-cycloserine (350 microM). To increase the productivity, the dcsJ gene, which might be responsible for the excretion, is connected downstream of the four genes, resulting in production of D-cycloserine at 660 microM. To repress the side catalytic activity of DcsD, i.e. the formation of L-cysteine from O-acetylserine and H2S, Escherichia coli chromosomal cysJ and cysK genes, encoding the sulfite reductase alpha subunit and O-acetylserine sulfhydrylase, respectively, are disrupted. The final strain produces 980 microM D-cycloserine
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Kumagai, T.; Koyama, Y.; Oda, K.; Noda, M.; Matoba, Y.; Sugiyama, M.
Molecular cloning and heterologous expression of a biosynthetic gene cluster for the antitubercular agent D-cycloserine produced by Streptomyces lavendulae
Antimicrob. Agents Chemother.
54
1132-1139
2010
Streptomyces lavendulae (D2Z027), Streptomyces lavendulae ATCC 11924 (D2Z027)
Manually annotated by BRENDA team
Uda, N.; Matoba, Y.; Kumagai, T.; Oda, K.; Noda, M.; Sugiyama, M
. Establishment of an in vitro D-cycloserine-synthesizing system by using O-ureido-L-serine synthase and D-cycloserine synthetase found in the biosynthetic pathway
Antimicrob. Agents Chemother.
57
2603-2612
2013
Streptomyces lavendulae (D2Z027), Streptomyces lavendulae ATCC 11924 (D2Z027)
Manually annotated by BRENDA team
Kumagai, T.; Ozawa, T.; Tanimoto, M.; Noda, M.; Matoba, Y.; Sugiyama, M.
High-level heterologous production of D-cycloserine by Escherichia coli
Appl. Environ. Microbiol.
81
7881-7887
2015
Streptomyces lavendulae (D2Z027), Streptomyces lavendulae ATCC 11924 (D2Z027)
Manually annotated by BRENDA team
Uda, N.; Matoba, Y.; Oda, K.; Kumagai, T.; Sugiyama, M.
The structural and mutational analyses of O-ureido-L-serine synthase necessary for D-cycloserine biosynthesis
FEBS J.
282
3929-3944
2015
Streptomyces lavendulae (D2Z027), Streptomyces lavendulae, Streptomyces lavendulae ATCC 11924 (D2Z027)
Manually annotated by BRENDA team