Information on EC 6.3.2.4 - D-Alanine-D-alanine ligase

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The expected taxonomic range for this enzyme is: Bacteria, Eukaryota

EC NUMBER
COMMENTARY
6.3.2.4
-
RECOMMENDED NAME
GeneOntology No.
D-Alanine-D-alanine ligase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
ATP + 2 D-alanine = ADP + phosphate + D-alanyl-D-alanine
show the reaction diagram
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
carboxamide formation
-
-
-
-
carboxylic acid amide formation
-
-
-
-
PATHWAY
KEGG Link
MetaCyc Link
D-Alanine metabolism
-
Metabolic pathways
-
Peptidoglycan biosynthesis
-
UDP-N-acetylmuramoyl-pentapeptide biosynthesis I (meso-DAP-containing)
-
UDP-N-acetylmuramoyl-pentapeptide biosynthesis II (lysine-containing)
-
SYSTEMATIC NAME
IUBMB Comments
D-alanine:D-alanine ligase (ADP-forming)
Involved with EC 6.3.2.7 (UDP-N-acetylmuramoyl-L-alanyl-D-glutamate---L-lysine ligase) or EC 6.3.2.13 (UDP-N-acetylmuramoyl-L-alanyl-D-glutamate---2,6-diaminopimelate ligase), EC 6.3.2.8 (UDP-N-acetylmuramate---L-alanine ligase), EC 6.3.2.9 (UDP-N-acetylmuramoyl-L-alanine---D-glutamate ligase) and EC 6.3.2.10 (UDP-N-acetylmuramoyl-tripeptide---D-alanyl-D-alanine ligase) in the synthesis of a cell-wall peptide (click here for diagram).
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
D-Ala-D-Ala ligase
-
-
-
-
D-Ala-D-Ala synthetase
-
-
-
-
D-Alanine:D-alanine ligase
-
-
-
-
D-Alanine:D-alanine ligase
-
-
D-alanyl-D-alanine ligase B
P07862
-
D-Alanyl-D-alanine synthetase
-
-
-
-
D-Alanylalanine synthetase
-
-
-
-
Ddl
Escherichia coli K12
-
-
-
Ddl
Oceanobacillus iheyensis JCM 11309
-
-
-
Ddl
Streptomyces lavendulae ATCC25233
-
-
-
Synthetase, D-alanylalanine
-
-
-
-
VanA
-
-
-
-
VanB ligase
-
-
-
-
DdlB
P07862
-
additional information
Q2N4T5
the enzyme is a member of the D-Ala-D-X ligase superfamily
CAS REGISTRY NUMBER
COMMENTARY
9023-63-6
-
ORGANISM
COMMENTARY
LITERATURE
SEQUENCE CODE
SEQUENCE DB
SOURCE
strain 168
-
-
Manually annotated by BRENDA team
Bacillus subtilis 168
strain 168
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
serovar L2
-
-
Manually annotated by BRENDA team
V583, VanB ligase with type B vancomycin resistance
-
-
Manually annotated by BRENDA team
Enterococcus faecalis R
strain R
-
-
Manually annotated by BRENDA team
isoform VanA
-
-
Manually annotated by BRENDA team
mutant enzyme that incorporats 2-hydroxy acids at terminal site instead of D-Ala
-
-
Manually annotated by BRENDA team
strain BM4416
-
-
Manually annotated by BRENDA team
Enterococcus faecium BM4416
strain BM4416
-
-
Manually annotated by BRENDA team
2 enzyme forms: ligase A and ligase B
-
-
Manually annotated by BRENDA team
strain JM105 containing recombinant plasmid pAT214, which expressed the VanA protein
-
-
Manually annotated by BRENDA team
strains BL21(DE3) and JM109
-
-
Manually annotated by BRENDA team
temperature-sensitive mutant strain ST-640, the low ligase is due to a mutation in the structural gene for D-alanine:D-alanine ligase (ADP)
-
-
Manually annotated by BRENDA team
two isoforms of DDl, DDlA and DDlB
SwissProt
Manually annotated by BRENDA team
wild-type and mutant enzyme forms
-
-
Manually annotated by BRENDA team
wild-type and Y216 mutant
SwissProt
Manually annotated by BRENDA team
Escherichia coli JM105
strain JM105 containing recombinant plasmid pAT214, which expressed the VanA protein
-
-
Manually annotated by BRENDA team
Escherichia coli K12
K12
-
-
Manually annotated by BRENDA team
strains SS1 and ATCC 43504, ddl gene
-
-
Manually annotated by BRENDA team
strains SS1, 26,695 and J99
UniProt
Manually annotated by BRENDA team
resistant to vancomycin
P71454
Uniprot
Manually annotated by BRENDA team
Lysinibacillus sphaericus 9602
9602
-
-
Manually annotated by BRENDA team
Oceanobacillus iheyensis JCM 11309
JCM 11309
-
-
Manually annotated by BRENDA team
type 12, L-form
-
-
Manually annotated by BRENDA team
strain ATCC25233
-
-
Manually annotated by BRENDA team
Streptomyces lavendulae ATCC25233
strain ATCC25233
-
-
Manually annotated by BRENDA team
strain ATCC 43589
UniProt
Manually annotated by BRENDA team
Thermotoga maritima ATCC 43589
-
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
physiological function
-
TN5 insertion mutant shows exopolysaccharides overproduction, decreased tolerance to saline conditions, altered cell morphology, and increased sensitivity to detergents
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
ATP + 2 D-Ala
ADP + phosphate + D-Ala-D-Ala
show the reaction diagram
-
-
-
-
?
ATP + 2 D-Ala
ADP + phosphate + D-Ala-D-Ala
show the reaction diagram
-
-
-
-
?
ATP + 2 D-Ala
ADP + phosphate + D-Ala-D-Ala
show the reaction diagram
-
-
-
-
?
ATP + 2 D-alanine
ADP + phosphate + D-alanyl-D-alanine
show the reaction diagram
-
Y216, S150, and E15 form a hydrogen-bonding triad that orients an omega-loop to close over the active site and also to orient substrate D-Ala1 (the first molecule of substrate that is activated by the enzyme protein). The bifunctional enzyme also catalyzes the formation of D-alanyl-D-lactate (D-alanine-(R)-lactate ligase)
-
-
?
ATP + Ala + Ala
?
show the reaction diagram
-
second enzyme in the three enzyme D-alanine branch of peptidoglycan biosynthesis
-
-
-
ATP + Ala + Ala
?
show the reaction diagram
-
enzyme involved in peptidoglycan precursor synthesis during sporulation
-
-
-
ATP + Ala + Ala
?
show the reaction diagram
-
a possible cellular role of VanA is to synthesize a modified cell-wall component, with D-Ala-D-Met or D-Ala-Phe instead of D-Ala-D-Ala, which is subsequently not recognized by vancomycin
-
-
-
ATP + Ala + Ala
?
show the reaction diagram
-
the finding that the reactions of EC 6.3.2.4 and EC 6.3.2.10 are reversible may represent a functional regulatory mechanism which determines the level of the lysine-containing UDPMurNAc-pentapeptide depending on the intracellular ATP/ADP ratio
-
-
-
ATP + Ala + Ala
?
show the reaction diagram
-
one step in peptidoglycan synthesis: the formation of D-Ala-D-Ala, the terminal dipeptide of the UDP-N-acetylmuramylpentapeptide
-
-
-
ATP + Ala + Ala
?
show the reaction diagram
-
second step in the biosynthesis of bacterial peptidoglycan
-
-
-
ATP + Ala + Ala
?
show the reaction diagram
Lysinibacillus sphaericus 9602
-
enzyme involved in peptidoglycan precursor synthesis during sporulation
-
-
-
ATP + beta-Ala
ADP + phosphate + ?
show the reaction diagram
P46805, -
at 60C activity is 1.3% of the activity with D-Ala, no activity at 37C
-
-
?
ATP + D-Ala + 2-hydroxybutanoate
ADP + phosphate + D-Ala-D-2-hydroxybutanoate
show the reaction diagram
-
-
-
-
ATP + D-Ala + 2-hydroxypentanoate
ADP + phosphate + D-Ala-D-2-hydroxypentanoate
show the reaction diagram
-
-
-
-
ATP + D-Ala + D-2-aminopentanoate
ADP + phosphate + D-Ala-D-2-aminopentanoate
show the reaction diagram
Escherichia coli, Escherichia coli JM105
-
-
-
-
-
ATP + D-Ala + D-Ala
ADP + phosphate + D-Ala-D-Ala
show the reaction diagram
-
-
-
-
ATP + D-Ala + D-Ala
ADP + phosphate + D-Ala-D-Ala
show the reaction diagram
-
-
-
-
ATP + D-Ala + D-Ala
ADP + phosphate + D-Ala-D-Ala
show the reaction diagram
-
-
-
-
ATP + D-Ala + D-Ala
ADP + phosphate + D-Ala-D-Ala
show the reaction diagram
-
-
-
-
ATP + D-Ala + D-Ala
ADP + phosphate + D-Ala-D-Ala
show the reaction diagram
-
-
-
-
ATP + D-Ala + D-Ala
ADP + phosphate + D-Ala-D-Ala
show the reaction diagram
-
-
-
-
ATP + D-Ala + D-Ala
ADP + phosphate + D-Ala-D-Ala
show the reaction diagram
-
-
-
-
ATP + D-Ala + D-Ala
ADP + phosphate + D-Ala-D-Ala
show the reaction diagram
-
-
-
-
ATP + D-Ala + D-Ala
ADP + phosphate + D-Ala-D-Ala
show the reaction diagram
-
-
-
-
ATP + D-Ala + D-Ala
ADP + phosphate + D-Ala-D-Ala
show the reaction diagram
-
-
-
-
ATP + D-Ala + D-Ala
ADP + phosphate + D-Ala-D-Ala
show the reaction diagram
-
-
-
-
ATP + D-Ala + D-Ala
ADP + phosphate + D-Ala-D-Ala
show the reaction diagram
-
-
-
-
ATP + D-Ala + D-Ala
ADP + phosphate + D-Ala-D-Ala
show the reaction diagram
P07862
-
-
-
ATP + D-Ala + D-Ala
ADP + phosphate + D-Ala-D-Ala
show the reaction diagram
-
-
-
-
ATP + D-Ala + D-Ala
ADP + phosphate + D-Ala-D-Ala
show the reaction diagram
-
-
-
-
ATP + D-Ala + D-Ala
ADP + phosphate + D-Ala-D-Ala
show the reaction diagram
-
-
-
-
ATP + D-Ala + D-Ala
ADP + phosphate + D-Ala-D-Ala
show the reaction diagram
-
-
-
-
ATP + D-Ala + D-Ala
ADP + phosphate + D-Ala-D-Ala
show the reaction diagram
-
-
-
-
ATP + D-Ala + D-Ala
ADP + phosphate + D-Ala-D-Ala
show the reaction diagram
-
-
-
-
ATP + D-Ala + D-Ala
ADP + phosphate + D-Ala-D-Ala
show the reaction diagram
-
-
-
-
ATP + D-Ala + D-Ala
ADP + phosphate + D-Ala-D-Ala
show the reaction diagram
-
-
-
-
ATP + D-Ala + D-Ala
ADP + phosphate + D-Ala-D-Ala
show the reaction diagram
-
-
-
-
ATP + D-Ala + D-Ala
ADP + phosphate + D-Ala-D-Ala
show the reaction diagram
-
-
-
-
ATP + D-Ala + D-Ala
ADP + phosphate + D-Ala-D-Ala
show the reaction diagram
-
-
-
-
ATP + D-Ala + D-Ala
ADP + phosphate + D-Ala-D-Ala
show the reaction diagram
-
-
-
-
ATP + D-Ala + D-Ala
ADP + phosphate + D-Ala-D-Ala
show the reaction diagram
-, P71454
-
-
-
ATP + D-Ala + D-Ala
ADP + phosphate + D-Ala-D-Ala
show the reaction diagram
-
-
-
-
?
ATP + D-Ala + D-Ala
ADP + phosphate + D-Ala-D-Ala
show the reaction diagram
-, P95114
-
-
-
?
ATP + D-Ala + D-Ala
ADP + phosphate + D-Ala-D-Ala
show the reaction diagram
-
r
-
-
ATP + D-Ala + D-Ala
ADP + phosphate + D-Ala-D-Ala
show the reaction diagram
-
r
-
-
ATP + D-Ala + D-Ala
ADP + phosphate + D-Ala-D-Ala
show the reaction diagram
-
r
-
-
ATP + D-Ala + D-Ala
ADP + phosphate + D-Ala-D-Ala
show the reaction diagram
Bacillus subtilis 168
-
-
-
-
ATP + D-Ala + D-Ala
ADP + phosphate + D-Ala-D-Ala
show the reaction diagram
Escherichia coli JM105
-
-
-
-
ATP + D-Ala + D-Ala
ADP + phosphate + D-Ala-D-Ala
show the reaction diagram
Enterococcus faecalis R
-
-
-
-
ATP + D-Ala + D-Ala
ADP + phosphate + D-Ala-D-Ala
show the reaction diagram
Thermotoga maritima ATCC 43589
-
-
-
-
?
ATP + D-Ala + D-lactate
ADP + phosphate + D-Ala-D-lactate
show the reaction diagram
-
-
-
-
ATP + D-Ala + D-lactate
ADP + phosphate + D-Ala-D-lactate
show the reaction diagram
-, P71454
-
-
-
ATP + D-Ala + D-lactate
ADP + phosphate + D-Ala-D-lactate
show the reaction diagram
-
-
depsipeptide D-Ala-D-lactate is responsible for the intrinsic resistance of Leuconostoc mesenteroides to vancomycin
-
?
ATP + D-Ala + D-lactate
ADP + phosphate + D-Ala-D-lactate
show the reaction diagram
-
enzyme uses both D-Ala and D-lactate as a substrate
-
-
?
ATP + D-Ala + D-lactate
ADP + phosphate + D-Ala-D-lactate
show the reaction diagram
Thermotoga maritima, Thermotoga maritima ATCC 43589
-
D-lactate is not a substrate for wild-type, but for mutants S137A/Y207F, S137F/Y207F, S137T/Y207F, S137G/Y207F, Y207F
-
-
?
ATP + D-Ala + D-Met
ADP + phosphate + D-Ala-D-Met
show the reaction diagram
-
-
-
-
-
ATP + D-Ala + D-Met
ADP + phosphate + D-Ala-D-Met
show the reaction diagram
Escherichia coli JM105
-
-
-
-
-
ATP + D-Ala + D-norleucine
ADP + phosphate + D-Ala-D-norleucine
show the reaction diagram
-
-
-
-
-
ATP + D-Ala + D-norleucine
ADP + phosphate + D-Ala-D-norleucine
show the reaction diagram
Escherichia coli JM105
-
-
-
-
-
ATP + D-Ala + D-Phe
ADP + phosphate + D-Ala-D-Phe
show the reaction diagram
-
-
-
-
-
ATP + D-Ala + D-Phe
ADP + phosphate + D-Ala-D-Phe
show the reaction diagram
Escherichia coli JM105
-
-
-
-
-
ATP + D-alanine
ADP + phosphate + D-alanyl-D-alanine
show the reaction diagram
Q5HEB7, -
-
-
-
?
ATP + D-alanine
ADP + phosphate + D-alanyl-D-alanine
show the reaction diagram
-
-
-
-
?
ATP + D-alanine
ADP + phosphate + D-alanyl-D-alanine
show the reaction diagram
-
-
-
?
ATP + D-alanine
ADP + phosphate + D-alanyl-D-alanine
show the reaction diagram
-
-
-
-
?
ATP + D-alanine
ADP + phosphate + D-alanyl-D-alanine
show the reaction diagram
P07862
-
-
-
?
ATP + D-alanine
ADP + phosphate + D-alanyl-D-alanine
show the reaction diagram
-
-
-
-
?
ATP + D-alanine
ADP + phosphate + D-alanyl-D-alanine
show the reaction diagram
Q9ZGN0
-
-
?
ATP + D-alanine
ADP + phosphate + D-alanyl-D-alanine
show the reaction diagram
-
-
-
?
ATP + D-alanine
ADP + phosphate + D-alanyl-D-alanine
show the reaction diagram
-
-
-
?
ATP + D-alanine
ADP + phosphate + D-alanyl-D-alanine
show the reaction diagram
-
-
-
?
ATP + D-alanine
ADP + phosphate + D-alanyl-D-alanine
show the reaction diagram
-
-
-
?
ATP + D-alanine
ADP + phosphate + D-alanyl-D-alanine
show the reaction diagram
-
-
-
-
?
ATP + D-alanine
ADP + phosphate + D-alanyl-D-alanine
show the reaction diagram
-
-
-
-
?
ATP + D-alanine
ADP + phosphate + D-alanyl-D-alanine
show the reaction diagram
P46805, -
-
-
-
?
ATP + D-alanine
ADP + phosphate + D-alanyl-D-alanine
show the reaction diagram
-
-
-
-
?
ATP + D-alanine
ADP + phosphate + D-alanyl-D-alanine
show the reaction diagram
-
-
-
-
?
ATP + D-alanine
ADP + phosphate + D-alanyl-D-alanine
show the reaction diagram
-
-
-
-
?
ATP + D-alanine
ADP + phosphate + D-alanyl-D-alanine
show the reaction diagram
-, Q2N4T5
-
-
-
?
ATP + D-alanine
ADP + phosphate + D-alanyl-D-alanine
show the reaction diagram
-
essential enzyme
-
?
ATP + D-alanine
ADP + phosphate + D-alanyl-D-alanine
show the reaction diagram
Q5HEB7, -
D-alanine:D-alanine ligase is an essential enzyme in bacterial cell wall biosynthesis and an important target for developing new antibiotics
-
-
?
ATP + D-alanine
ADP + phosphate + D-alanyl-D-alanine
show the reaction diagram
-, Q2N4T5
the enzyme shows relatively weak binding affinity and poor catalytic activity against the substrate D-Ala in vitro, active site structure, overview
-
-
?
ATP + D-alanine
ADP + phosphate + D-alanyl-D-alanine
show the reaction diagram
Oceanobacillus iheyensis JCM 11309
-
-
-
-
?
ATP + D-alanine
ADP + phosphate + D-alanyl-D-alanine
show the reaction diagram
Enterococcus faecium BM4416
-
-
-
?
ATP + D-alanine
ADP + phosphate + D-alanyl-D-alanine
show the reaction diagram
Streptomyces lavendulae ATCC25233
-
-
-
-
?
ATP + D-alanine
ADP + phosphate + D-alanyl-D-alanine
show the reaction diagram
Escherichia coli K12
-
-
-
-
?
ATP + D-alanine + D-serine
ADP + D-alanyl-D-serine + D-alanyl-D-alanine + D-seryl-D-serine
show the reaction diagram
-
-
-
-
?
ATP + D-Arg
ADP + phosphate + D-Arg-D-Arg
show the reaction diagram
P46805, -
at 60C activity is 0.43% of the activity with D-Ala, no activity at 37C
-
-
?
ATP + D-Asn
ADP + phosphate + D-Asn-D-Asn
show the reaction diagram
P46805, -
at 60C activity is 0.22% of the activity with D-Ala, no activity at 37C
-
-
?
ATP + D-Asp
ADP + phosphate + D-Asp-D-Asp
show the reaction diagram
P46805, -
at 60C activity is 0.051% of the activity with D-Ala, no activity at 37C
-
-
?
ATP + D-Cys
ADP + phosphate + D-Cys-D-Cys
show the reaction diagram
P46805, -
at 60C activity is 29% of the activity with D-Ala
-
-
?
ATP + D-Gln
ADP + phosphate + D-Gln-D-Gln
show the reaction diagram
P46805, -
at 60C activity is 0.56% of the activity with D-Ala, no activity at 37C
-
-
?
ATP + D-Glu
ADP + phosphate + D-Glu-D-Glu
show the reaction diagram
P46805, -
at 60C activity is 0.012% of the activity with D-Ala, no activity at 37C
-
-
?
ATP + D-His
ADP + phosphate + D-His-D-His
show the reaction diagram
P46805, -
at 60C activity is 0.49% of the activity with D-Ala, no activity at 37C
-
-
?
ATP + D-Ile
ADP + phosphate + D-Ile-D-Ile
show the reaction diagram
P46805, -
at 60C activity is 0.36% of the activity with D-Ala, no activity at 37C
-
-
?
ATP + D-Leu
ADP + phosphate + D-Leu-D-Leu
show the reaction diagram
P46805, -
at 60C activity is 0.31% of the activity with D-Ala, no activity at 37C
-
-
?
ATP + D-Lys
ADP + phosphate + D-Lys-D-Lys
show the reaction diagram
P46805, -
at 60C activity is 0.6% of the activity with D-Ala, no activity at 37C
-
-
?
ATP + D-Met
ADP + phosphate + D-Met-D-Met
show the reaction diagram
P46805, -
at 60C activity is 0.34% of the activity with D-Ala, no activity at 37C
-
-
?
ATP + D-Phe
ADP + phosphate + D-Phe-D-Phe
show the reaction diagram
P46805, -
at 60C activity is 0.31% of the activity with D-Ala, no activity at 37C
-
-
?
ATP + D-Pro
ADP + phosphate + D-Pro-D-Pro
show the reaction diagram
P46805, -
at 60C activity is 0.29% of the activity with D-Ala, no activity at 37C
-
-
?
ATP + D-Ser
ADP + phosphate + D-Ser-D-Ser
show the reaction diagram
P46805, -
at 60C activity is 16% of the activity with D-Ala
-
-
?
ATP + D-serine
ADP + phosphate + D-alanyl-D-serine
show the reaction diagram
-
-
-
?
ATP + D-Thr
ADP + phosphate + D-Thr-D-Thr
show the reaction diagram
P46805, -
at 60C activity is 2.2% of the activity with D-Ala
-
-
?
ATP + D-Trp
ADP + phosphate + D-Trp-D-Trp
show the reaction diagram
P46805, -
at 60C activity is 0.1% of the activity with D-Ala, no activity at 37C
-
-
?
ATP + D-Val
ADP + phosphate + D-Val-D-Val
show the reaction diagram
P46805, -
at 60C activity is 0.43% of the activity with D-Ala, no activity at 37C
-
-
?
ATP + Gly
ADP + phosphate + Gly-Gly
show the reaction diagram
P46805, -
at 60C activity is 3.6% of the activity with D-Ala
-
-
?
beta-alanine + beta-alanine + ATP
beta-alanyl-beta-alanine + ADP + phosphate
show the reaction diagram
P46805, -
-
1.3% of the activity with D-serine
-
?
D-alanine + D-alanine + ATP
D-alanyl-D-alanine + ADP + phosphate
show the reaction diagram
P46805, -
-
-
-
?
D-cycloserine
?
show the reaction diagram
-
-
-
-
?
D-cycloserine
?
show the reaction diagram
Streptomyces lavendulae, Streptomyces lavendulae ATCC25233
-
-
-
-
?
D-cysteine + ATP
ADP + D-cysteinyl-D-cysteine
show the reaction diagram
-
-
-
-
?
D-cysteine + D-cysteine + ATP
D-cysteinyl-D-cysteine + ADP + phosphate
show the reaction diagram
P46805, -
-
29% of the activity with D-serine
-
?
D-serine + ATP
ADP + D-serinyl-D-serine
show the reaction diagram
-
-
-
-
?
D-serine + D-serine + ATP
D-seryl-D-serine + ADP + phosphate
show the reaction diagram
P46805, -
-
16% of the activity with D-serine
-
?
D-threonine + ATP
ADP + D-threonyl-D-threonine
show the reaction diagram
-
-
-
-
?
D-threonine + D-threonine + ATP
D-threonyl-D-threonine + ADP + phosphate
show the reaction diagram
P46805, -
-
2.2% of the activity with D-serine
-
?
dipeptides + ATP
?
show the reaction diagram
Oceanobacillus iheyensis, Oceanobacillus iheyensis JCM 11309
-
-
-
-
?
glycine + D-alanine + ATP
glycyl-D-alanine + ADP + phosphate
show the reaction diagram
P46805, -
-
3.6% of the activity with D-serine
-
?
glycine + glycine + ATP
ADP + Gly-Gly + phosphate
show the reaction diagram
-
-
-
-
?
additional information
?
-
-
the enzyme is also capable of synthesizing fluorinated dipeptides
-
-
-
additional information
?
-
P07862
DDl is an essential enzyme in bacterial cell wall biosynthesis
-
-
-
additional information
?
-
-, Q2N4T5
no activity with D-Ser, Gly, and D-lactate
-
-
-
additional information
?
-
P46805, -
substrate specificity expands at high temperature. At 37C, enzyme shows reactivity only for D-alanine, D-serine, D-threonine, D-cysteine and glycine. At 60C, substrates additionally include D-lysine, D-glutamine, D-histidine, D-arginine, D-valine, D-isoleucine, D-methionine, D-leucine, D-phenylalanine, D-proline, and D-asparagine, all below 1% of the activity with D-alanine
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
ATP + Ala + Ala
?
show the reaction diagram
-
second enzyme in the three enzyme D-alanine branch of peptidoglycan biosynthesis
-
-
-
ATP + Ala + Ala
?
show the reaction diagram
-
enzyme involved in peptidoglycan precursor synthesis during sporulation
-
-
-
ATP + Ala + Ala
?
show the reaction diagram
-
a possible cellular role of VanA is to synthesize a modified cell-wall component, with D-Ala-D-Met or D-Ala-Phe instead of D-Ala-D-Ala, which is subsequently not recognized by vancomycin
-
-
-
ATP + Ala + Ala
?
show the reaction diagram
-
the finding that the reactions of EC 6.3.2.4 and EC 6.3.2.10 are reversible may represent a functional regulatory mechanism which determines the level of the lysine-containing UDPMurNAc-pentapeptide depending on the intracellular ATP/ADP ratio
-
-
-
ATP + Ala + Ala
?
show the reaction diagram
-
one step in peptidoglycan synthesis: the formation of D-Ala-D-Ala, the terminal dipeptide of the UDP-N-acetylmuramylpentapeptide
-
-
-
ATP + Ala + Ala
?
show the reaction diagram
-
second step in the biosynthesis of bacterial peptidoglycan
-
-
-
ATP + Ala + Ala
?
show the reaction diagram
Lysinibacillus sphaericus 9602
-
enzyme involved in peptidoglycan precursor synthesis during sporulation
-
-
-
ATP + D-alanine
ADP + phosphate + D-alanyl-D-alanine
show the reaction diagram
-
-
-
-
?
ATP + D-alanine
ADP + phosphate + D-alanyl-D-alanine
show the reaction diagram
-
-
-
?
ATP + D-alanine
ADP + phosphate + D-alanyl-D-alanine
show the reaction diagram
-
-
-
-
?
ATP + D-alanine
ADP + phosphate + D-alanyl-D-alanine
show the reaction diagram
P07862
-
-
-
?
ATP + D-alanine
ADP + phosphate + D-alanyl-D-alanine
show the reaction diagram
-
-
-
-
?
ATP + D-alanine
ADP + phosphate + D-alanyl-D-alanine
show the reaction diagram
Q9ZGN0
-
-
?
ATP + D-alanine
ADP + phosphate + D-alanyl-D-alanine
show the reaction diagram
-
-
-
?
ATP + D-alanine
ADP + phosphate + D-alanyl-D-alanine
show the reaction diagram
-
-
-
?
ATP + D-alanine
ADP + phosphate + D-alanyl-D-alanine
show the reaction diagram
-
-
-
?
ATP + D-alanine
ADP + phosphate + D-alanyl-D-alanine
show the reaction diagram
-
-
-
-
?
ATP + D-alanine
ADP + phosphate + D-alanyl-D-alanine
show the reaction diagram
-
-
-
-
?
ATP + D-alanine
ADP + phosphate + D-alanyl-D-alanine
show the reaction diagram
-
-
-
-
?
ATP + D-alanine
ADP + phosphate + D-alanyl-D-alanine
show the reaction diagram
-
-
-
-
?
ATP + D-alanine
ADP + phosphate + D-alanyl-D-alanine
show the reaction diagram
-
-
-
-
?
ATP + D-alanine
ADP + phosphate + D-alanyl-D-alanine
show the reaction diagram
-, Q2N4T5
-
-
-
?
ATP + D-alanine
ADP + phosphate + D-alanyl-D-alanine
show the reaction diagram
-
essential enzyme
-
?
ATP + D-alanine
ADP + phosphate + D-alanyl-D-alanine
show the reaction diagram
Q5HEB7, -
D-alanine:D-alanine ligase is an essential enzyme in bacterial cell wall biosynthesis and an important target for developing new antibiotics
-
-
?
ATP + D-alanine
ADP + phosphate + D-alanyl-D-alanine
show the reaction diagram
Oceanobacillus iheyensis JCM 11309
-
-
-
-
?
ATP + D-alanine
ADP + phosphate + D-alanyl-D-alanine
show the reaction diagram
Enterococcus faecium BM4416
-
-
-
?
ATP + D-alanine
ADP + phosphate + D-alanyl-D-alanine
show the reaction diagram
Streptomyces lavendulae ATCC25233
-
-
-
-
?
ATP + D-alanine
ADP + phosphate + D-alanyl-D-alanine
show the reaction diagram
Escherichia coli K12
-
-
-
-
?
additional information
?
-
P07862
DDl is an essential enzyme in bacterial cell wall biosynthesis
-
-
-
COFACTOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
INHIBITORS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
(1-Aminoethyl)boronic acid
-
time-dependent, slow binding
(2Z)-N-(2-chloro-6-methylphenyl)-2-ethynyl-3-hydroxybut-2-enamide
P07862
-
(3-Amino-2-oxoalkyl)phosphonic acids
-
e.g. (3(R)-amino-2-oxobutyl)phosphonic acid and the corresponding aza analogue
(E)-N,N'-bis(2-chloroethyl)diazene-1,2-dicarboxamide
-
-
(E)-N,N'-bis(pyridin-3-ylmethyl)diazene-1,2-dicarboxamide
-
-
(E)-N-(2-chloroethyl)-N'-(4-isopropylphenyl)diazene-1,2-dicarboxamide
-
-
(E)-N-(2-chloroethyl)-N'-(pyridin-2-ylmethyl)diazene-1,2-dicarboxamide
-
-
(E)-N-(2-chloroethyl)-N'-(pyridin-4-ylmethyl)diazene-1,2-dicarboxamide
-
-
(E)-N-(3-chlorophenyl)-N'-(pyridin-3-ylmethyl)diazene-1,2-dicarboxamide
-
-
(E)-N-(3-chlorophenyl)-N'-(pyridin-4-ylmethyl)diazene-1,2-dicarboxamide
-
-
(E)-N-(4-fluorophenyl)-N'-(pyridin-4-ylmethyl)diazene-1,2-dicarboxamide
-
-
(E)-N-(4-sec-butylphenyl)-N'-(2-chloroethyl)diazene-1,2-dicarboxamide
-
-
(E)-N-cyclohexyl-N'-(pyridin-4-ylmethyl)diazene-1,2-dicarboxamide
-
-
(E)-N-phenyl-N'-(pyridin-2-ylmethyl)diazene-1,2-dicarboxamide
-
-
(E)-N-phenyl-N'-(pyridin-3-ylmethyl)diazene-1,2-dicarboxamide
-
-
(E)-N-phenyl-N'-(pyridin-4-ylmethyl)diazene-1,2-dicarboxamide
-
-
(E)-N-[4-(butan-2-yl)phenyl]-N'-(2-chloroethyl)diazene-1,2-dicarboxamide
-
-
1-[[(4-fluorophenyl)sulfonyl]amino]-3-(morpholin-4-yl)propan-2-yl dihydrogen phosphate
-
0.5 mM, 75% inhibition
1-[[(4-fluorophenyl)sulfonyl]amino]-3-(morpholin-4-yl)propan-2-yl dihydrogen phosphate
-
0.5 mM, 77% inhibition
1-[[(4-fluorophenyl)sulfonyl]amino]-3-(morpholin-4-yl)propan-2-yl phenyl hydrogen phosphate
-
0.5 mM, 65% inhibition
1-[[(4-methoxyphenyl)sulfonyl]amino]-3-(morpholin-4-yl)propan-2-yl dihydrogen phosphate
-
0.5 mM, 83% inhibition
2-aminoethylphosphonate
-
weak
3-chloro-2,2-dimethyl-N-[4(trifluoromethyl)phenyl]propanamide
Q5HEB7
the inhibitor binds to a hydrophobic pocket at the interface of the first and the third domain. This inhibitor-binding pocket is adjacent to the first D-alanine substrate site but does not overlap with any substrate sites
alpha-Aminophosphonamidic acid
-
time-dependent inhibition in presence of ATP
Aminoalkylphosphinate
-
-
-
apigenin
-
4',5,7-trihydroxyflavone, inhibition mechanism, competitive with respect to the substrate ATP and non-competitive to the substrate D-Ala
D-(1-Aminoethyl)phosphinic acid
-
competitive
D-(1-Aminoethyl)phosphonic acid
-
time-dependent inhibition in presence of ATP
D-(1-Aminoethyl)phosphonic acid
-
DL-
D-(1-Aminoethyl)phosphonic acid
-
DL-
D-3-[(1-Aminoethyl)phosphinyl]-2-heptylpropionic acid
-
potent active site directed inhibitor, competitive with D-Ala, time-dependent inhibition in the presence of ATP
D-Ala-D-2-hydroxybutanoate phosphonate
P07862
-
D-Ala-D-Ala phosphinate
P07862
-
D-Alanyl-D-alanine
-
-
D-cycloserine
-
-
D-cycloserine
Q9ZGN0
0.2 mg/ml, approx. 50% inhibition, 0.8 mg/ml, approx. 80% inhibition
D-cycloserine
-
0.2 mg/ml, approx. 60% inhibition, 0.8 mg/ml, approx. 95% inhibition
D-cycloserine
-
weak inhibition
D-cycloserine
P07862
; competitive inhibitor
D-cycloserine
-, P95114
preferential and weak inhibition at the second, lower-affinity binding site. D-cycloserine binding is tighter at higher ATP concentrations
diazenocarboxamide
P07862
-
H-1004
P07862
slight inhibition
leflunomide
P07862
an antirheumatic drug
LFM-A12
P07862
an analog of the Leflunomide metabolite A771726
LFM-A13
P07862
Brutons's tyrosine kinase inhibitor, an analog of the Leflunomide metabolite A771726
LY294002
P07862
slight inhibition
N-(2,5-dibromophenyl)-2-oxopropanamide
P07862
-
Olomoucine
P07862
-
Phosphinates
-
-
-
Phosphinates
-
weak inhibition of ligase B of E. coli and Van A from Enterococcus faecium, strong inhibition of ligase A from E. coli
-
Phosphonate dipeptide analogs
-
weak inhibition of ligase B from E. coli and Van A from Enterococcus faecium
-
piceatannol
P07862
slight inhibition
quercetin
P07862
-
quercetin
-
i.e. 3,3',4',5,7-pentahydroxyflavone, inhibition mechanism, competitive with respect to the substrate ATP and non-competitive to the substrate D-Ala
Tabtoxinine
-
no inhibition by the lactam analogues
tyrphostin 47
P07862
competitive versus ATP
tyrphostin 51
P07862
mixed-type inhibition
Wortmannin
P07862
slight inhibition
[1(S)-Aminoethyl][(2RS)2-carboxy-1-octyl]phosphinic acid
-
classical slow-binding
[1(S)-Aminoethyl][2-carboxy-2(R)-methyl-1-ethyl]phosphinic acid
-
ATP-dependent, slow-binding, enzyme-inhibitor half-life is 17 days at 37C, mechanism of inactivation involves phosphorylation of the enzyme-bound inhibitor by ATP to form a phosphoryl-phosphinate adduct
[3-chloro-2,2-dimethyl-N-4(trimethylfluoro)phenyl]propanamide
P07862
-
methylphosphinophosphate
-
strong inhibition
-
additional information
-
large reduction in binding affinity of the VanA mutant enzyme for all the phosphorus-containing analogs has significant implications for the design of inhibitors specific for this enzyme
-
additional information
P07862
antibiotic inhibitor design, bisubstrate inhibitors that block the ATP and D-Ala binding sites exhibit enhanced selectivity and potency profiles by preferentially inhibiting DDl over kinases, overview
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
A771726
P07862
a leflunomide metabolite, slightly activating
N-(2,5-dibromophenyl)-2-oxopropanamide
P07862
slightly activating
KM VALUE [mM]
KM VALUE [mM] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
33
-
2-aminopentanoate
-
reaction with D-Ala + ATP
3
-
2-hydroxybutanoate
-
-
8.3
-
2-hydroxypentanoate
-
-
0.00087
-
ATP
-, Q2N4T5
pH 8.0, 30C
0.00242
-
ATP
-, Q2N4T5
pH 9.0, 30C
0.008
-
ATP
-
mutant enzyme Y216K
0.033
-
ATP
-
mutant enzyme Y216F
0.049
-
ATP
-
wild-type enzyme
0.055
-
ATP
-
mutant enzyme E15Q
0.06
-
ATP
Q5HEB7
-
0.161
-
ATP
-
mutant enzyme H63Q
0.179
-
ATP
-
mutant enzyme S150A
2.4
-
ATP
-
mutant enzyme K144A
2.5
-
ATP
-
mutant enzyme K144T
40
-
ATP
-
ligase B
0.0012
-
D-Ala
-
N-terminal Ala, wild-type enzyme
0.0033
-
D-Ala
-
N-terminal Ala, ligase B
0.0057
-
D-Ala
-
C-terminal Ala, ligase A
0.26
-
D-Ala
-
N-terminal Ala, mutant enzyme Y216F
0.43
-
D-Ala
-
N-terminal Ala, mutant enzyme E15Q, mutant enzyme Y216K
0.49
-
D-Ala
-
N-terminal Ala, mutant enzyme L282R
0.55
-
D-Ala
-
N-terminal Ala, mutant enzyme H63Q
0.55
-
D-Ala
-
D-Ala, C-terminal, ligase A
0.76
-
D-Ala
-
N-terminal Ala, mutant enzyme S150A
1.05
-
D-Ala
-
C-terminal Ala, mutant enzyme D257N
1.13
-
D-Ala
-
C-terminal Ala, wild-type enzyme
1.2
-
D-Ala
-
C-terminal Ala, ligase B
1.2
-
D-Ala
-
D-Ala, N-terminal Ala, + D-Ala, VanB
3.4
-
D-Ala
-
N-terminal Ala
5.4
-
D-Ala
-
reaction with D-Met + ATP
6.4
-
D-Ala
-
reaction with D-Phe + ATP
20.9
-
D-Ala
-
C-terminal Ala, mutant enzyme L282R
22.8
-
D-Ala
-
C-terminal Ala, mutant enzyme K144A, reaction with 5 mM ATP
22.9
-
D-Ala
-
C-terminal Ala, mutant enzyme K144A, reaction with 15 mM ATP
25.7
-
D-Ala
-
C-terminal Ala, mutant enzyme Y216F
34
-
D-Ala
-
C-terminal Ala, reaction with D-Ala + ATP, VanB
38
-
D-Ala
-
ATP, ligase A
38
-
D-Ala
-
C-terminal Ala
38
-
D-Ala
-
-
43.7
-
D-Ala
-
C-terminal Ala, mutant enzyme E15Q
57.5
-
D-Ala
-
C-terminal Ala, mutant enzyme H63Q
60.4
-
D-Ala
-
C-terminal Ala, mutant enzyme S150A
70.3
-
D-Ala
-
C-terminal Ala, mutant enzyme K144T, reaction with 5 mM ATP
86
-
D-Ala
-
C-terminal Ala, mutant enzyme K144T, reaction with 15 mM ATP
0.003
-
D-alanine
-
37C, KM-value for D-alanine1 (the first molecule of substrate that is activated by the enzyme molecule) , wild-type enzyme, pH 7.5
0.004
-
D-alanine
-
37C, KM-value for D-alanine1 (the first molecule of substrate that is activated by the enzyme molecule), wild-type enzyme, pH 9.2
0.11
-
D-alanine
-
37C, KM-value for D-alanine1 (the first molecule of substrate that is activated by the enzyme molecule), wild-type enzyme, pH 6.0
0.51
-
D-alanine
-
37C, KM-value for D-alanine1 (the first molecule of substrate that is activated by the enzyme molecule), mutant enzyme E15Q, pH 7.5; 37C, KM-value for D-alanine1 (the first molecule of substrate that is activated by the enzyme molecule), mutant enzyme E15Q, pH 9.2
0.85
-
D-alanine
-
37C, KM-value for D-alanine1 (the first molecule of substrate that is activated by the enzyme molecule), mutant enzyme S150A, pH 7.5
1.1
-
D-alanine
-
37C, KM-value for D-alanine2 (the second molecule of substrate that is activated by the enzyme molecule), wild-type enzyme, pH 9.2
1.13
-
D-alanine
-
-
1.49
-
D-alanine
-, Q2N4T5
pH 9.0, 30C
1.89
-
D-alanine
-, Q2N4T5
pH 8.0, 30C
2
-
D-alanine
-
37C, KM-value for D-alanine2 (the second molecule of substrate that is activated by the enzyme molecule), wild-type enzyme, pH 7.5
4.8
-
D-alanine
-
37C, KM-value for D-alanine1 (the first molecule of substrate that is activated by the enzyme molecule), mutant enzyme Y216F, pH 9.2
6.2
-
D-alanine
-
37C, KM-value for D-alanine1 (the first molecule of substrate that is activated by the enzyme molecule), mutant enzyme S150A, pH 6.0
8
-
D-alanine
-
37C, KM-value for D-alanine2 (the second molecule of substrate that is activated by the enzyme molecule), wild-type enzyme, pH 6.0
11
-
D-alanine
-
37C, KM-value for D-alanine1 (the first molecule of substrate that is activated by the enzyme molecule), mutant enzyme E15Q, pH 6.0
16
-
D-alanine
-
37C, KM-value for D-alanine1 (the first molecule of substrate that is activated by the enzyme molecule), mutant enzyme Y216F, pH 7.5
44
-
D-alanine
-
37C, KM-value for D-alanine1 (the first molecule of substrate that is activated by the enzyme molecule) , mutant enzyme S150A, pH 9.2
65
-
D-alanine
-
37C, KM-value for D-alanine2 (the second molecule of substrate that is activated by the enzyme molecule), mutant enzyme E15Q, pH 9.2
74
-
D-alanine
-
37C, KM-value for D-alanine2 (the second molecule of substrate that is activated by the enzyme molecule), mutant enzyme E15Q, pH 7.5
80
-
D-alanine
-
37C, KM-value for D-alanine2 (the second molecule of substrate that is activated by the enzyme molecule), mutant enzyme S150A, pH 7.5
82
-
D-alanine
-
37C, KM-value for D-alanine2 (the second molecule of substrate that is activated by the enzyme molecule), mutant enzyme E15Q, pH 6.0
140
-
D-alanine
-
37C, KM-value for D-alanine2 (the second molecule of substrate that is activated by the enzyme molecule), mutant enzyme S150A, pH 6.0
150
-
D-alanine
-
37C, KM-value for D-alanine1 (the first molecule of substrate that is activated by the enzyme molecule) , mutant enzyme Y216F, pH 6.0
450
-
D-alanine
-
37C, KM-value for D-alanine2 (the second molecule of substrate that is activated by the enzyme molecule), mutant enzyme Y216F, pH 6.0
630
-
D-alanine
-
37C, KM-value for D-alanine2 (the second molecule of substrate that is activated by the enzyme molecule), mutant enzyme Y216F, pH 7.5
1100
-
D-alanine
-
37C, KM-value for D-alanine2 (the second molecule of substrate that is activated by the enzyme molecule), mutant enzyme S150A, pH 9.2
1200
-
D-alanine
-
37C, KM-value for D-alanine2 (the second molecule of substrate that is activated by the enzyme molecule), mutant enzyme Y216F, pH 9.2
11.4
-
D-lactate
-
-
15
-
D-Norleucine
-
reaction with D-Ala + ATP
6
-
D-Phe
-
reaction with D-Ala + ATP
56
-
D-serine
-
-
additional information
-
additional information
-
-
-
additional information
-
additional information
-
-
-
additional information
-
additional information
-, P71454
-
-
additional information
-
additional information
-
kinetic analysis
-
additional information
-
additional information
-, Q2N4T5
kinetics of wild-type and mutant enzymes
-
TURNOVER NUMBER [1/s]
TURNOVER NUMBER MAXIMUM[1/s]
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
1.9
-
ATP
-, Q2N4T5
pH 8.0-9.0, 30C
4.92
-
D-Ala
-
-
7.4
-
D-Ala
-
ligase A
17
-
D-Ala
-
ligase B
1.67
-
D-alanine
-
-
1.9
-
D-alanine
-, Q2N4T5
pH 8.0-9.0, 30C
3.3
-
D-alanine
-
37C, mutant enzyme E15Q, pH 6.0; 37C, mutant enzyme S150A, pH 6.0
7.5
-
D-alanine
-
37C, mutant enzyme Y216F, pH 6.0
10.5
-
D-alanine
-
37C, mutant enzyme Y216F, pH 7.5
11.83
-
D-alanine
-
37C, wild-type enzyme, pH 6.0
13.7
-
D-alanine
-
37C, mutant enzyme E15Q, pH 7.5
14.7
-
D-alanine
-
37C, wild-type enzyme, pH 7.5
16.3
-
D-alanine
-
37C, mutant enzyme S150A, pH 7.5
18.3
-
D-alanine
-
37C, mutant enzyme E15Q, pH 9.2; 37C, mutant enzyme S150A, pH 9.2
20
-
D-alanine
-
37C, mutant enzyme Y216F, pH 9.2
26.7
-
D-alanine
-
37C, wild-type enzyme, pH 9.2
31.2
-
D-alanine
-
-
48.5
-
D-alanine
-
-
2.6
-
D-serine
-
-
additional information
-
additional information
-
-
-
additional information
-
additional information
-
turnover numbers of wild-type and mutant enzyme forms
-
additional information
-
additional information
-
-
-
additional information
-
additional information
-, P71454
-
-
additional information
-
additional information
-
-
-
kcat/KM VALUE [1/mMs-1]
kcat/KM VALUE [1/mMs-1] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
7.96
-
ATP
-
-
22040
1.4
-
D-alanine
-
37C, mutant enzyme S150A, kcat/Km(D-alanine2), pH 6.0. D-Alanine2 is the second molecule of substrate that is activated by the enzyme molecule
9048
2.4
-
D-alanine
-
37C, mutant enzyme E15Q, kcat/Km(D-alanine2), pH 6.0. D-Alanine2 is the second molecule of substrate that is activated by the enzyme molecule
9048
3
-
D-alanine
-
37C, mutant enzyme Y216F, kcat/Km(D-alanine2), pH 6.0. D-Alanine2 is the second molecule of substrate that is activated by the enzyme molecule
9048
11
-
D-alanine
-
37C, mutant enzyme E15Q, kcat/Km(D-alanine2), pH 7.5. D-Alanine2 is the second molecule of substrate that is activated by the enzyme molecule
9048
12
-
D-alanine
-
37C, mutant enzyme S150A, kcat/Km(D-alanine2), pH 7.5. D-Alanine2 is the second molecule of substrate that is activated by the enzyme molecule
9048
17
-
D-alanine
-
37C, mutant enzyme E15Q, kcat/Km(D-alanine2), pH 9.2. D-Alanine2 is the second molecule of substrate that is activated by the enzyme molecule
9048
26
-
D-alanine
-
37C, mutant enzyme S150A, kcat/Km(D-alanine2), pH 9.2. D-Alanine2 is the second molecule of substrate that is activated by the enzyme molecule
9048
39
-
D-alanine
-
37C, mutant enzyme Y216F, kcat/Km(D-alanine2), pH 7.5. D-Alanine2 is the second molecule of substrate that is activated by the enzyme molecule
9048
89
-
D-alanine
-
37C, wild-type enzyme, kcat/Km(D-alanine2), pH 6.0. D-Alanine2 is the second molecule of substrate that is activated by the enzyme molecule
9048
260
-
D-alanine
-
37C, mutant enzyme Y216F, kcat/Km(D-alanine2), pH 9.2. D-Alanine2 is the second molecule of substrate that is activated by the enzyme molecule
9048
440
-
D-alanine
-
37C, wild-type enzyme, kcat/Km(D-alanine2), pH 7.5. D-Alanine2 is the second molecule of substrate that is activated by the enzyme molecule
9048
1500
-
D-alanine
-
37C, wild-type enzyme, kcat/Km(D-alanine2), pH 9.2. D-Alanine2 is the second molecule of substrate that is activated by the enzyme molecule
9048
Ki VALUE [mM]
Ki VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.04
-
3-chloro-2,2-dimethyl-N-[4(trifluoromethyl)phenyl]propanamide
Q5HEB7
-
0.031
-
apigenin
-
pH 7.4, 25C, versus ATP
0.0807
-
apigenin
-
pH 7.4, 25C, versus ATP
0.085
-
apigenin
-
pH 7.4, 25C, versus D-Ala
0.1195
-
apigenin
-
pH 7.4, 25C, versus D-Ala
0.06
-
D-Alanyl-D-alanine
-
-
0.002
-
D-cycloserine
-
-
0.185
-
D-cycloserine
P07862
-
0.92
-
D-cycloserine
-
-
0.185
-
LFM-A13
P07862
-
0.215
-
N-(2,5-dibromophenyl)-2-oxopropanamide
P07862
-
1.8
-
Olomoucine
P07862
-
0.0043
-
quercetin
-
pH 7.4, 25C, versus ATP
0.0097
-
quercetin
-
pH 7.4, 25C, versus ATP
0.0101
-
quercetin
-
pH 7.4, 25C, versus D-Ala
0.028
-
quercetin
-
pH 7.4, 25C, versus D-Ala
0.29
-
tyrphostin 47
P07862
-
1.4
-
LY294002
P07862
-
additional information
-
additional information
-
inhibition kinetics at pH 7.4 and 25C
-
additional information
-
additional information
-
inhibition kinetics
-
IC50 VALUE [mM]
IC50 VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.133
-
(E)-N,N'-bis(2-chloroethyl)diazene-1,2-dicarboxamide
-
-
0.123
-
(E)-N,N'-bis(pyridin-3-ylmethyl)diazene-1,2-dicarboxamide
-
-
0.049
-
(E)-N-(2-chloroethyl)-N'-(4-isopropylphenyl)diazene-1,2-dicarboxamide
-
-
0.119
-
(E)-N-(2-chloroethyl)-N'-(pyridin-2-ylmethyl)diazene-1,2-dicarboxamide
-
-
0.236
-
(E)-N-(2-chloroethyl)-N'-(pyridin-4-ylmethyl)diazene-1,2-dicarboxamide
-
-
0.015
-
(E)-N-(3-chlorophenyl)-N'-(pyridin-3-ylmethyl)diazene-1,2-dicarboxamide
-
; pH 8.0, 37C
0.033
-
(E)-N-(3-chlorophenyl)-N'-(pyridin-4-ylmethyl)diazene-1,2-dicarboxamide
-
; pH 8.0, 37C
0.073
-
(E)-N-(4-fluorophenyl)-N'-(pyridin-4-ylmethyl)diazene-1,2-dicarboxamide
-
-
0.025
-
(E)-N-(4-sec-butylphenyl)-N'-(2-chloroethyl)diazene-1,2-dicarboxamide
-
-
0.121
-
(E)-N-cyclohexyl-N'-(pyridin-4-ylmethyl)diazene-1,2-dicarboxamide
-
-
0.111
-
(E)-N-phenyl-N'-(pyridin-2-ylmethyl)diazene-1,2-dicarboxamide
-
-
0.036
-
(E)-N-phenyl-N'-(pyridin-3-ylmethyl)diazene-1,2-dicarboxamide
-
; pH 8.0, 37C
0.106
-
(E)-N-phenyl-N'-(pyridin-4-ylmethyl)diazene-1,2-dicarboxamide
-
-
0.025
-
(E)-N-[4-(butan-2-yl)phenyl]-N'-(2-chloroethyl)diazene-1,2-dicarboxamide
-
pH 8.0, 37C
0.1327
-
apigenin
-
pH 7.4, 25C
0.163
-
apigenin
-
pH 7.4, 25C
0.37
-
D-cycloserine
-, P95114
pH not specified in the publication, temperature not specified in the publication
0.0199
-
quercetin
-
pH 7.4, 25C
0.0485
-
quercetin
-
pH 7.4, 25C
SPECIFIC ACTIVITY [µmol/min/mg]
SPECIFIC ACTIVITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
0.071
-
P46805, -
substrate beta-alanine, 60C
0.12
-
P46805, -
substrate D-threonine, 60C
0.19
-
-
mutant S137F/Y207F, substrates D-Ala + D-lactate, 60C, pH 7.5
0.2
-
P46805, -
substrate glycine, 60C
0.39
-
-
mutant Y207F, substrates D-Ala + D-lactate, 60C, pH 7.5
0.42
-
-
mutant S137A/Y207F, substrates D-Ala + D-lactate, 60C, pH 7.5
0.88
-
P46805, -
substrate D-serine, 60C
0.95
-
-
mutant S137F/Y207F, substrate D-Ala, 60C, pH 7.5
1.2
-
-
mutant S137G/Y207F, substrates D-Ala + D-lactate, 60C, pH 7.5
1.6
-
P46805, -
substrate D-cysteine, 60C
1.75
-
-
mutant S137T/Y207F, substrate D-Ala, 60C, pH 7.5
4.22
-
-
wild-type, substrate D-Ala, 60C, pH 7.5
5.5
-
P46805, -
substrate D-alanine, 60C
6.489
-
-
mutant S137A/Y207F, substrate D-Ala, 60C, pH 7.5
9.66
-
-
mutant S137G/Y207F, substrate D-Ala, 60C, pH 7.5
12.3
-
-
ligase A
17.22
-
-
mutant Y207F, substrate D-Ala, 60C, pH 7.5
18.9
-
-
-
31
-
-
ligase B
pH OPTIMUM
pH MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
9
-
-, Q2N4T5
above
pH RANGE
pH RANGE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
6
9.2
-
higher DDL activity at pH 9.2 than at pH 6.0-7.5
additional information
-
-, Q2N4T5
pH profile
TEMPERATURE OPTIMUM
TEMPERATURE OPTIMUM MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
50
-
-, Q2N4T5
-
60
-
P46805, -
-
TEMPERATURE RANGE
TEMPERATURE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
30
70
P46805, -
30C: about 70% of maximal activity, 70C: about 50% of maximal activity
SOURCE TISSUE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
SOURCE
-
the activity decays at the end of the vegetative growth and increases again later in the sporulating process
Manually annotated by BRENDA team
Lysinibacillus sphaericus 9602
-
the activity decays at the end of the vegetative growth and increases again later in the sporulating process
-
Manually annotated by BRENDA team
-
the activity decays at the end of the vegetative growth and increases again later in the sporulating process
Manually annotated by BRENDA team
Lysinibacillus sphaericus 9602
-
the activity decays at the end of the vegetative growth and increases again later in the sporulating process
-
Manually annotated by BRENDA team
PDB
SCOP
CATH
ORGANISM
Burkholderia ambifaria (strain MC40-6)
Burkholderia pseudomallei (strain 1710b)
Burkholderia xenovorans (strain LB400)
Coxiella burnetii (strain RSA 493 / Nine Mile phase I)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Leuconostoc mesenteroides subsp. mesenteroides (strain ATCC 8293 / NCDO 523)
Salmonella typhimurium (strain LT2 / SGSC1412 / ATCC 700720)
Salmonella typhimurium (strain LT2 / SGSC1412 / ATCC 700720)
Staphylococcus aureus (strain COL)
Staphylococcus aureus (strain COL)
Staphylococcus aureus (strain COL)
Staphylococcus aureus (strain COL)
Streptococcus mutans serotype c (strain ATCC 700610 / UA159)
Thermus thermophilus (strain HB8 / ATCC 27634 / DSM 579)
Thermus thermophilus (strain HB8 / ATCC 27634 / DSM 579)
Thermus thermophilus (strain HB8 / ATCC 27634 / DSM 579)
Thermus thermophilus (strain HB8 / ATCC 27634 / DSM 579)
Thermus thermophilus (strain HB8 / ATCC 27634 / DSM 579)
Thermus thermophilus (strain HB8 / ATCC 27634 / DSM 579)
Xanthomonas oryzae pv. oryzae (strain KACC10331 / KXO85)
Xanthomonas oryzae pv. oryzae (strain KACC10331 / KXO85)
Xanthomonas oryzae pv. oryzae (strain MAFF 311018)
Xanthomonas oryzae pv. oryzae (strain MAFF 311018)
Xanthomonas oryzae pv. oryzae (strain MAFF 311018)
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
?
-
x * 39271, calculation from nucleotide sequence; x * 42000, SDS-PAGE
?
-
x * 38000, SDS-PAGE
dimer
-, Q2N4T5
-
additional information
-, Q2N4T5
3_10-helix, including residues from Gly306 to Leu312, near the D-Ala binding region in the C-terminal domain probably participates in D-Ala binding and conformational change of the enzyme
Crystallization/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
co-crystallized with an S,R-methylphosphinate and adenosine triphosphate, at 2.3 A resolution
-
complexed with a D-Ala-D-2-hydroxybutanoate phosphonate, and Y216F mutant ligase complexed with a D-Ala-D-Ala phosphinate, at 2.2A and 1.9A resolution
P07862
in ternary complex with ADP and D-alanyl-D-alanine, to 1.4 A resolution, and with the ligands ATP and D-alanyl-D-alanine, representing the product-inhibited complex, to 1.5 A resolution
-
recombinant enzyme, 4-8 mg/ml protien in 20 mM Tris-HCl, pH 8.0, 300 mM NaCl, 2 mM MgCl2, hanging drop vapour diffusion method, 4C, versus a reservoir solution containing 0.1M HEPES, pH 7.5, 10% PEG 6000, 5% MPD, 4 months, X-ray diffraction structure determination and analysisat 2.4 A resolution, molecular replacement
-, Q2N4T5
molecular docking study on the orientations of substrates. Residue Arg301 has a dual function in a sequential reaction mechanism, i.e. substrate orientation in subsite 2 as well as stabilization of the transition state. With D-lactate a bifurcated H-bond from Arg301 to the R-OH of D-lactate may account for its orientation and nucleophile activation. This orientation is observed when the guanidino side chain of this residue is flexible. D-Ala adopts an orientation that utilizes H-bonding to water 2882 and the D-Ala phosphate in subsite 1. Both of these orientations provide mechanisms of deprotonation and place the nucleophile within 3.2 A of the electrophilic carbonyl of the D-Ala phosphate intermediate for formation of the transition state
-
t 2.1 A resoluion. Ddl is a dimer and consists of three discrete domains. The ligand binding cavity is at the intersection of all three domains and conjoined by several loop regions. The nucleotide and D-alanine binding pockets are flexible, requiring significant structural rearrangement of the bordering regions for entry and binding of both ATP and D-Ala molecules. D-cycloserine interacts with Ddl in a manner similar to that observed for D-Ala. Each ligand binds to two binding sites that have significant differences in affinity, with the first binding site exhibiting high affinity
-, P95114
crystal structure of Staphylococcus aureus D-alanine:D-alanine ligase and its cocrystal structures with 3-chloro-2,2-dimethyl-N-4(trifluoromethyl)phenylpropanamide and with ADP at resolutions of 2.0 A, 2.2 A, and 2.6 A, respectively
Q5HEB7
sitting-drop vapour diffusion method. Cube-shaped crystal diffracted to 2.4 A. The crystal belong to space group P3(1)21 or P3(2)21, with unit-cell parameters a = b = 79.50, c = 108.97 A. There is one molecule per asymmetric unit
-
hanging-drop vapor-diffusion method, structure of the enzyme is determined in the absence of substrates (open conformation)
-
structure of unliganded enzyme to 2.3 A resolution, of Ddl with adenylyl imidodiphosphate to 2.6 A resolution, of Ddl with ADP to 2.2 A resolution, of Ddl with ADP and D-Ala to 1.9 A resolution, and of Ddl with ATP and D-Ala-D-Ala to 2.3 A resolution. The central domain rotates as a rigid body towards the active site in a cumulative manner in concert with the local conformational change of three flexible loops depending upon substrate or product binding, resulting in an overall structural change from the open to the closed form through semi-open and semi-closed forms
Q5SHZ3, -
TEMPERATURE STABILITY
TEMPERATURE STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
10
90
P46805, -
-
90
-
P46805, -
15 min, stable up to
Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
recombinant Ddl
-
recombinant His-tagged wild-type and mutant enzymes from Escherichia coli strain BL21(DE3)
-, Q2N4T5
Cloned/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
expressed in Escherichia coli ATM697 and ATM718 as a fusion protein MurC-Ddl
-
Van B ligase is overproduced in Escherichia coli HB101 harboring recombinant plasmid pAT204
-
expression in Escherichia coli
-
expression in Escherichia coli BL21
-
placed under the control of the lac and lambdaPl promoter
-
expression of N-terminally His-tagged wild-type and mutant enzymes in Escherichia coli strain BL21(DE3)
-, Q2N4T5
overproduction in Escherichia coli, the vancomycin resistant enzyme has Phe261 instead of Tyr. The Tyr to Phe substitution on the active site omega-loop in the D-Ala-D-Ala ligases is a molecular indicator of both the ability to make D-Ala-D-Lac and intrinsic resistance to the vancomycin class of glycopeptide antibiotics
-, P71454
overexpression of Ddl in Mycobacterium smegmatis
Q9ZGN0
expression in Escherichia coli
-, P95114
overexpression of Ddl in Mycobacterium smegmatis
-
expression in Escherichia coli BL21
-
subcloned behind the tac promoter in the plasmid pKK223-3, expression in Escherichia coli JM105
-
ddl is amplified from Streptococcus mutans genomic DNA and cloned into the expression vector pET28a. The protein is expressed in soluble form in Escherichia coli strain BL21 (DE3)
-
expressed in Escherichia coli BL21
-
expression in Escherichia coli BL21
-
expression in Escherichia coli
P46805, -
expression in Escherichia coli BL21
-
expression in Escherichia coli
-
EXPRESSION
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
presence of transcriptional coupling between ddlB gene associated with peptidoglycan biosynthesis and the fts genes required to control cell division
-
ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
E15Q
-
mutant enzyme with negligible depsipeptide synthetase activity. The mutant uniquely activates D-Lac as the electrophilic rather than the nucleophilic partner for condensation with D-Ala to make a regioisomeric D-Lac-D-Ala, an amide rather than an ester product
S150A
-
mutant has gained depsipeptide (D-Ala-D-Lac, D-Ala-D-hydroxybutyrate) ligase activity with dipeptide/depsipeptide partition ratios that mimic the pH behavior of VanA (D-alanine(R)-lactate ligase)
Y216F
-
mutant has gained depsipeptide (D-Ala-D-Lac, D-Ala-D-hydroxybutyrate) ligase activity with dipeptide/depsipeptide partition ratios that mimic the pH behavior of VanA (D-alanine(R)-lactate ligase)
I16V
-, Q2N4T5
site-directed mutagenesis of an active site mutant, mutant kinetics compared to the wild-type structure
L241F
-, Q2N4T5
site-directed mutagenesis of an active site mutant, mutant kinetics compared to the wild-type structure
L241Y
-, Q2N4T5
site-directed mutagenesis of an active site mutant, mutant kinetics compared to the wild-type structure
L308T
-, Q2N4T5
site-directed mutagenesis of an active site mutant, mutant kinetics compared to the wild-type structure
Y311S
-, Q2N4T5
site-directed mutagenesis of an active site mutant, mutant kinetics compared to the wild-type structure
S137A/Y207F
-
higher D-alanyl-D-lactate and lower D-alanyl-D-alanine synthase activity than mutant Y207F. Broad substrate specificity toward D-amino acids, accepts D-lactate and D,L-isoleucine as substrate
S137F/Y207F
-
about 20% of wild-type activity. Accepts D-lactate as substrate
S137G/Y207F
-
about 200% of wild-type activity. Accepts D-lactate as substrate
S137T/Y207F
-
about 40% of wild-type activity. Does not accept D-lactate as substrate
Y201F
-
increase in activity compared to wild-type, mutant is not able to synthesize D-alanyl-D-lactate
Y207F
-
mutant is able to synthesize D-alanyl-D-lactate
S137A/Y207F
Thermotoga maritima ATCC 43589
-
higher D-alanyl-D-lactate and lower D-alanyl-D-alanine synthase activity than mutant Y207F. Broad substrate specificity toward D-amino acids, accepts D-lactate and D,L-isoleucine as substrate
-
S137F/Y207F
Thermotoga maritima ATCC 43589
-
about 20% of wild-type activity. Accepts D-lactate as substrate
-
S137T/Y207F
Thermotoga maritima ATCC 43589
-
about 40% of wild-type activity. Does not accept D-lactate as substrate
-
Y201F
Thermotoga maritima ATCC 43589
-
increase in activity compared to wild-type, mutant is not able to synthesize D-alanyl-D-lactate
-
Y207F
Thermotoga maritima ATCC 43589
-
mutant is able to synthesize D-alanyl-D-lactate
-
additional information
-
insertion in the middle of the ddl gene is responsible for inactivation of D-alanine-D-alanine ligase in strain BM4416
additional information
-
9 clinical isolates that show high resistance to vancomycin have mutations in the Ddl gene, lack of growth of these mutants in the absence of vancomycin is most probably due to a complete loss of Ddl activity
additional information
Enterococcus faecium BM4416
-
insertion in the middle of the ddl gene is responsible for inactivation of D-alanine-D-alanine ligase in strain BM4416
-
L282R
-
11fold decrease in kcat for D-alanine, 18fold increase in Km for D-alanine, 23fold decrease in Km for D-serine, 9fold drop in kcat for D-serine
additional information
-
mutant enzymes at K144, K215, and E270 in the ATP binding site, at E15, S150, H63, and R255 in the first D-Ala subsite, and at Y216, S281, L282, and D257 in the second D-Ala subsite. Mutant enzymes E270Q, K215A, R255A, and D257N retain very low or no detectable activity. Mutants enzyme Y216F shows substantial retention of activity
APPLICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
analysis
-
assay method for screening for effectors of alanine racemase and/or D-alanine:D-alanine ligase
analysis
Enterococcus faecalis R
-
assay method for screening for effectors of alanine racemase and/or D-alanine:D-alanine ligase
-
drug development
P07862
the enzyme is a target for antibiotic inhibitor development, overview
synthesis
-
D-alanine-D-alanine ligase is a biocatalyst for synthesizing D-amino acid dipeptides, use of a thermostable ATP regeneration system