Information on EC 6.3.3.4 - (carboxyethyl)arginine beta-lactam-synthase

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The enzyme appears in viruses and cellular organisms

EC NUMBER
COMMENTARY hide
6.3.3.4
-
RECOMMENDED NAME
GeneOntology No.
(carboxyethyl)arginine beta-lactam-synthase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
ATP + L-N2-(2-carboxyethyl)arginine = AMP + diphosphate + deoxyamidinoproclavaminate
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
cyclization
-
-
-
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formation of cyclic amides
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-
-
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PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
clavulanate biosynthesis
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Clavulanic acid biosynthesis
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Biosynthesis of antibiotics
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-
SYSTEMATIC NAME
IUBMB Comments
L-N2-(2-carboxyethyl)arginine cyclo-ligase (AMP-forming)
Forms part of the pathway for the biosythesis of the beta-lactamase inhibitor clavulanate in Streptomyces clavuligerus. It has been proposed [3] that L-N2-(2-carboxyethyl)arginine is first converted into an acyl-AMP by reaction with ATP and loss of diphosphate, and that the beta-lactam ring is then formed by the intramolecular attack of the beta-nitrogen on the activated carboxy group.
CAS REGISTRY NUMBER
COMMENTARY hide
68247-54-1
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
metabolism
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
ATP + (2'R)-methyl-L-N2-(2-carboxyethyl)arginine
?
show the reaction diagram
-
-
-
-
?
ATP + (2'S)-ethyl-L-N2-(2-carboxyethyl)arginine
?
show the reaction diagram
-
-
-
-
?
ATP + (2'S)-methyl-L-N2-(2-carboxyethyl)arginine
?
show the reaction diagram
-
-
-
-
?
ATP + L-N2-(2-carboxyethyl)arginine
AMP + diphosphate + deoxyamidinoproclavaminate
show the reaction diagram
N2-(carboxyethyl)-L-arginine + ATP
AMP + diphosphate + deoxyamidinoproclavaminate
show the reaction diagram
additional information
?
-
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no activity with (2'R)-ethyl-L-N2-(2-carboxyethyl)arginine
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-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
ATP + L-N2-(2-carboxyethyl)arginine
AMP + diphosphate + deoxyamidinoproclavaminate
show the reaction diagram
N2-(carboxyethyl)-L-arginine + ATP
AMP + diphosphate + deoxyamidinoproclavaminate
show the reaction diagram
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
deoxyamidinoproclavaminate
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product inhibition
diphosphate
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product inhibition
N2-(carboxymethyl)-L-arginine
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competitive to N2-(carboxyethyl)-L-arginine
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.04 - 1.9
(2'R)-methyl-L-N2-(2-carboxyethyl)arginine
0.04 - 0.06
(2'S)-ethyl-L-N2-(2-carboxyethyl)arginine
0.06 - 1.2
(2'S)-methyl-L-N2-(2-carboxyethyl)arginine
0.153
ATP
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pH 7.5
0.037 - 1
L-N2-(2-carboxyethyl)arginine
0.22
N2-(carboxyethyl)-L-arginine
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pH 7.5
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.014 - 0.07
(2'R)-methyl-L-N2-(2-carboxyethyl)arginine
0.0023 - 0.004
(2'S)-ethyl-L-N2-(2-carboxyethyl)arginine
0.013 - 0.34
(2'S)-methyl-L-N2-(2-carboxyethyl)arginine
0.016 - 0.87
L-N2-(2-carboxyethyl)arginine
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
54500
-
x * 54500, deduced from gene sequence
56000
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x * 56000, SDS-PAGE
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-20°C, 50 mM Tris-HCl, 10% glycerol, 2 mM dithiothreitol, 0.01 mM EDTA, pH 7.5, stable
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Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
recombinant protein expressed in E. coli
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Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
homologous to Class B asparagine synthases
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Streptomyces venezuelae YJ028 is utilized as the heterologous host for the expression of four structural clavulanic acid biosynthesis genes, which encode carboxyethylarginine synthase (ceas2), beta-lactam synthetase (bls2), clavaminate synthase (cas2), and proclavaminate amidinohydrolase (pah2). The genes are cloned into pIBR25 expression vector containing ermE promoter to generate pBS4. The cas2 gene is also cloned into pSET152 to generate pCas2. It is then integrated into the genome of Streptomyces venezuelae YJ028
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
H447A
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the mutant shows severely reduced turnover number compared to the wild type enzyme
V446A
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the mutant shows reduced turnover number compared to the wild type enzyme
V446G
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the mutant shows strongly reduced turnover number compared to the wild type enzyme
additional information
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disruption mutant, complete loss of clavulanic acid production, accumulation of N2-(carboxyethyl)-L-arginine, but no effect on synthesis of penicillin or cephamycin
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
synthesis