Information on EC 6.1.1.13 - D-alanine-poly(phosphoribitol) ligase

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The enzyme appears in viruses and cellular organisms

EC NUMBER
COMMENTARY hide
6.1.1.13
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RECOMMENDED NAME
GeneOntology No.
D-alanine-poly(phosphoribitol) ligase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
ATP + D-alanine + poly(ribitol phosphate) = AMP + diphosphate + O-D-alanyl-poly(ribitol phosphate)
show the reaction diagram
A thioester bond is formed transiently between D-alanine and the sulfhydryl group of the 4'-phosphopantetheine prosthetic group of D-alanyl carrier protein during the activation of the alanine. Involved in the synthesis of teichoic acids
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Acid-thiol ligation
adenylation
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thiolation
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PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
D-Alanine metabolism
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SYSTEMATIC NAME
IUBMB Comments
D-alanine:poly(phosphoribitol) ligase (AMP-forming)
A thioester bond is formed transiently between D-alanine and the sulfhydryl group of the 4'-phosphopantetheine prosthetic group of D-alanyl carrier protein during the activation of the alanine. Involved in the synthesis of teichoic acids.
CAS REGISTRY NUMBER
COMMENTARY hide
9023-65-8
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ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
laboratory strains R6, D39, and Rx,and the clinical isolate TIGR4, dltA operon, gene dltA
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Manually annotated by BRENDA team
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
ATP + D-2-amino butyric acid + diphosphate
?
show the reaction diagram
activity and specificity of DltA is investigated using the ATP-pyrophosphate exchange assay. Enzyme shows only minor activity 13% with D-amino butyric acid
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?
ATP + D-2-amino-n-butyric acid + membrane fragments
D-2-Amino-n-butryl-membrane fragments + AMP + diphosphate
show the reaction diagram
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not L-2-amino-n-butyric acid
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ATP + D-Ala + acyl-carrier protein
D-Alanyl-acyl-carrier protein + AMP + diphosphate
show the reaction diagram
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acyl carrier protein of E. coli, Vibrio harveyi, Saccharopolyspora erythraea, not of Bacillus subtilis, Spinacia oleracea
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ATP + D-Ala + D-alanyl carrier protein
D-Alanyl-D-alanyl carrier protein + AMP + diphosphate
show the reaction diagram
ATP + D-Ala + diphosphate
?
show the reaction diagram
ATP + D-Ala + hydroxylamine
D-Alanine hydroxamate + AMP + diphosphate
show the reaction diagram
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D-Ala can be substituted by D-2-amino-n-butyric acid with 14.6% and D-Ser with 7.5% efficiency
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ATP + D-Ala + membrane fragments
D-Alanyl-membrane fragments + AMP + diphosphate
show the reaction diagram
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ATP can be substituted by ADP, GTP, CTP, UTP, not by AMP, D-Ala cannot be substituted by L-Ala
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ATP + D-alanine + D-alanyl lipoteichoic acid
AMP + diphosphate + D-alanyl lipoteichoic acid
show the reaction diagram
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?
ATP + D-alanine + D-alanyl teichoic acid
AMP + diphosphate + D-alanyl teichoic acid
show the reaction diagram
ATP + D-alanine + poly(ribitol phosphate)
AMP + diphosphate + O-D-alanyl-poly(ribitol phosphate)
show the reaction diagram
ATP + D-Ser + diphosphate
?
show the reaction diagram
activity and specificity of DltA is investigated using the ATP-pyrophosphate exchange assay. Enzyme shows only minor activity 13% with D-Ser
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?
ATP + diphosphate
ATP + diphosphate
show the reaction diagram
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ATP + L-Ala + diphosphate
?
show the reaction diagram
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?
D-Alanine + ATP + ?
?
show the reaction diagram
additional information
?
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the enzyme is required for incorporation of D-alanine in teichoic acids in Gram-positive bacteria, confering resistance to cationic antimicrobial peptides nisin and gallidermin in Streptococcus pneumoniae, enzymes of D-alanine metabolism are encoded in the dltA operon, a functional dlt operon confers resistance to nisin and gallidermin
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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 + D-alanine + D-alanyl lipoteichoic acid
AMP + diphosphate + D-alanyl lipoteichoic acid
show the reaction diagram
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?
ATP + D-alanine + D-alanyl teichoic acid
AMP + diphosphate + D-alanyl teichoic acid
show the reaction diagram
ATP + D-alanine + poly(ribitol phosphate)
AMP + diphosphate + O-D-alanyl-poly(ribitol phosphate)
show the reaction diagram
D-Alanine + ATP + ?
?
show the reaction diagram
additional information
?
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the enzyme is required for incorporation of D-alanine in teichoic acids in Gram-positive bacteria, confering resistance to cationic antimicrobial peptides nisin and gallidermin in Streptococcus pneumoniae, enzymes of D-alanine metabolism are encoded in the dltA operon, a functional dlt operon confers resistance to nisin and gallidermin
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Ba2+
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Ba2+ can replace Mg2+ in activity enhancement
Ca2+
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Ca2+ can replace Mg2+ in activity enhancement
Co2+
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Co2+ can replace Mg2+ in activity enhancement
K+
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K+ can replace Mg2+ in activity enhancement
Na+
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Na+ can replace Mg2+ in activity enhancement
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
5'-O-[N-(D-alanyl)-sulfamoyl]adenosine
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inhibits D-Ala adenylylation by DltA in vitro
D-2-Amino-n-butyric acid hydroxamate
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DL-2-Amino-n-butyric acid hydroxamate
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DL-Alanine amide
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DL-Alanine hydroxamate
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additional information
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
DltD
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facilitator of D-Ala ligation to the carrier protein Dcp
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DTT
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stimulation
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.01 - 3.3
ATP
0.85
D-2-amino-n-butyric acid
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0.018 - 70
D-Ala
0.13
diphosphate
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ATP-diphosphate exchange reaction
6.6 - 14.4
L-Ala
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.011 - 0.215
ATP
0.025 - 0.103
D-Ala
0.11 - 0.12
L-Ala
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.000232
5'-O-[N-(D-alanyl)-sulfamoyl]adenosine
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5 - 8
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substrates D-Ala + ATP + D-alanyl carrier protein
6.6 - 7
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substrates D-Ala + ATP + acyl carrier protein of Escherichia coli
7 - 8
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substrates D-Ala + hydroxylamine + ATP
7.5 - 8
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ATP-diphosphate exchange reaction
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
PDB
SCOP
CATH
ORGANISM
UNIPROT
Bacillus cereus (strain ATCC 14579 / DSM 31 / JCM 2152 / NBRC 15305 / NCIMB 9373 / NRRL B-3711)
Bacillus cereus (strain ATCC 14579 / DSM 31 / JCM 2152 / NBRC 15305 / NCIMB 9373 / NRRL B-3711)
Bacillus cereus (strain ATCC 14579 / DSM 31 / JCM 2152 / NBRC 15305 / NCIMB 9373 / NRRL B-3711)
Bacillus cereus (strain ATCC 14579 / DSM 31 / JCM 2152 / NBRC 15305 / NCIMB 9373 / NRRL B-3711)
Bacillus subtilis (strain 168)
Bacillus subtilis (strain 168)
Bacillus subtilis (strain 168)
Bacillus subtilis (strain 168)
Bacillus subtilis (strain 168)
Streptococcus pyogenes serotype M6 (strain ATCC BAA-946 / MGAS10394)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
39000
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gel filtration
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
crystal structure of a DltA is determined at 2.0 A resolution in complex with the D-alanine adenylate intermediate of the first reaction. Despite the low level of sequence similarity, the DltA structure resembles known structures of adenylation domains such as the acetyl-CoA synthetase. The enantiomer selection appears to be enhanced by the medium-sized side chain of Cys-269
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the crystal structure of Bacillus cereus D-alanyl carrier protein ligase (DltA) is determined in complex with ATP to 1.9 A resolution
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protein is crystallized in the presence of substrates D-Ala, ATP and MgCl2. The structures of the reported DltA reveal the determinants for D-Ala substrate specificity, and confirm that the PCP-activating domains are able to adopt multiple conformational states, in this case corresponding to the thiolation reaction
sitting drop vapor diffusion method
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TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
45
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45% loss of activity in 15 min, ATP and/or D-alanyl carrier protein enhance thermostability, acyl carrier protein facilitates inactivation
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-10°C, ammonium sulfate fraction stable for 6 months
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-20°C, chromatographed fraction loses 25% of activity in 1 week
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Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
partial
using Ni-NTA chromatography
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Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
dltA, enzymes of D-alanine metabolism are encoded in the dltA operon, DNA and amino acid sequence determination and analysis, a functional dlt operon confers resistance to nisin and gallidermin
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expressed in Escherichia coli as a His-tagged fusion protein
overexpression of DltA and DltC in Escherichia coli
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the pET28a vector is used
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
C269A
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C269A mutation relaxes D-Ala preference. Km (mM): (D-Ala) 3.1, (L-Ala) 6.6, kcat (1/sec): (D-Ala) 0.103, (L-Ala) 0.12
D383N
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mutant, an invariant amino residue in the ATP-binding pocket is choosen for mutagenesis studies
E298Q
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mutant, an invariant amino residue in the ATP-binding pocket is choosen for mutagenesis studies
R397Q
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mutant, an invariant amino residue in the ATP-binding pocket is choosen for mutagenesis studies
C268A
mutant shows strong preference for D-Ala as a substrate, a high activity is also observed towards D-amino butyric acid (56%). Most significantly, the variant accepts the L-amino acids LAla (9.7%), L-amino butyric acid (6%) and L-Ser (7%). Turnover of D-Ser is reduced to 3%
C268D
mutant demonstrates a similar specificity profile to wild-type DltA, although with significantly lower activity
additional information
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insertional inactivation of dltA in D39 and Rx yielded pairs of dltA-deficient and dltA-proficient strains, phenotypes with enhanced sensitivity to the cationic antimicrobial peptides nisin and gallidermin, overview
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