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 hide
6.3.2.4
-
RECOMMENDED NAME
GeneOntology No.
D-Alanine-D-alanine ligase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
ATP + 2 D-alanine = ADP + phosphate + D-alanyl-D-alanine
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
carboxamide formation
-
-
-
-
carboxylic acid amide formation
-
-
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
D-Alanine metabolism
-
-
Metabolic pathways
-
-
peptidoglycan biosynthesis
-
-
Peptidoglycan biosynthesis
-
-
UDP-N-acetylmuramoyl-pentapeptide biosynthesis I (meso-diaminopimelate 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).
CAS REGISTRY NUMBER
COMMENTARY hide
9023-63-6
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
strain 168
-
-
Manually annotated by BRENDA team
strain 168
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
serovar L2
-
-
Manually annotated by BRENDA team
strain R
-
-
Manually annotated by BRENDA team
strain BM4416
-
-
Manually annotated by BRENDA team
K12
-
-
Manually annotated by BRENDA team
9602
-
-
Manually annotated by BRENDA team
9602
-
-
Manually annotated by BRENDA team
JCM 11309
-
-
Manually annotated by BRENDA team
JCM 11309
-
-
Manually annotated by BRENDA team
type 12, L-form
-
-
Manually annotated by BRENDA team
strain ATCC25233
-
-
Manually annotated by BRENDA team
strain ATCC25233
-
-
Manually annotated by BRENDA team
strain BP-1
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
pv. oryzae
UniProt
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
-
inhibition of Ddl prevents bacterial growth
physiological function
additional information
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 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
ATP + Ala + Ala
?
show the reaction diagram
ATP + beta-Ala
ADP + phosphate + ?
show the reaction diagram
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
-
-
-
-
-
ATP + D-Ala + D-Ala
ADP + phosphate + D-Ala-D-Ala
show the reaction diagram
ATP + D-Ala + D-lactate
ADP + phosphate + D-Ala-D-lactate
show the reaction diagram
ATP + D-Ala + D-Met
ADP + phosphate + D-Ala-D-Met
show the reaction diagram
-
-
-
-
-
ATP + D-Ala + D-norleucine
ADP + phosphate + D-Ala-D-norleucine
show the reaction diagram
-
-
-
-
-
ATP + D-Ala + D-Phe
ADP + phosphate + D-Ala-D-Phe
show the reaction diagram
-
-
-
-
-
ATP + D-alanine
ADP + phosphate + D-alanyl-D-alanine
show the reaction diagram
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
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
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
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
at 60C activity is 29% of the activity with D-Ala
-
-
?
ATP + D-Gln
ADP + phosphate + D-Gln-D-Gln
show the reaction diagram
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
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
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
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
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
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
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
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
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
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
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
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
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
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
-
1.3% of the activity with D-serine
-
?
D-alanine + D-alanine + ATP
D-alanyl-D-alanine + ADP + phosphate
show the reaction diagram
-
-
-
?
D-cycloserine
?
show the reaction diagram
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
-
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
-
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
-
2.2% of the activity with D-serine
-
?
dipeptides + ATP
?
show the reaction diagram
glycine + D-alanine + ATP
glycyl-D-alanine + ADP + phosphate
show the reaction diagram
-
3.6% of the activity with D-serine
-
?
glycine + glycine + ATP
ADP + Gly-Gly + phosphate
show the reaction diagram
additional information
?
-
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 + 2 D-alanine
ADP + phosphate + D-alanyl-D-alanine
show the reaction diagram
ATP + Ala + Ala
?
show the reaction diagram
ATP + D-alanine
ADP + phosphate + D-alanyl-D-alanine
show the reaction diagram
additional information
?
-
P07862
DDl is an essential enzyme in bacterial cell wall biosynthesis
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-
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(1-Aminoethyl)boronic acid
-
time-dependent, slow binding
(2Z)-N-(2-chloro-6-methylphenyl)-2-ethynyl-3-hydroxybut-2-enamide
-
(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-dimethyl-9H-carbazole
-
-
1,4-dimethyl-9H-carbazole-3-carbaldehyde
-
-
1-(2-amino-6-phenylpyrido[2,3-d]pyrimidin-7-yl)-3-tert-butylurea
-
-
1-(3-chloro-8-methoxy-11H-indolo[3,2-c]quinolin-9-yl)-N,N-dimethylmethanamine
-
-
1-tert-butyl-3-[6-(2,6-dichlorophenyl)-2-[[3-(morpholin-4-yl)propyl]amino]pyrido[2,3-d]pyrimidin-7-yl]urea
-
-
1-tert-butyl-3-[6-(3,5-dimethoxyphenyl)-2-[[3-(dimethylamino)propyl]amino]pyrido[2,3-d]pyrimidin-7-yl]urea
-
-
1-tert-butyl-3-[6-(3,5-dimethoxyphenyl)-2-[[3-(morpholin-4-yl)propyl]amino]pyrido[2,3-d]pyrimidin-7-yl]urea
-
-
1-[2-amino-6-(1,3-benzodioxol-5-yl)pyrido[2,3-d]pyrimidin-7-yl]-3-tert-butylurea
-
-
1-[2-amino-6-(2,6-dibromophenyl)pyrido[2,3-d]pyrimidin-7-yl]-3-tert-butylurea
-
-
1-[2-amino-6-(2-bromo-6-fluorophenyl)pyrido[2,3-d]pyrimidin-7-yl]-3-tert-butylurea
-
-
1-[2-amino-6-(3,5-dimethoxyphenyl)pyrido[2,3-d]pyrimidin-7-yl]-3-tert-butylurea
-
-
1-[2-amino-6-[3,5-bis(trifluoromethyl)phenyl]pyrido[2,3-d]pyrimidin-7-yl]-3-tert-butylurea
-
-
1-[4-[(6-chloro-2-methoxyacridin-9-yl)amino]phenyl]-3-(dimethylamino)propan-1-ol
-
-
1-[[(4-fluorophenyl)sulfonyl]amino]-3-(morpholin-4-yl)propan-2-yl dihydrogen phosphate
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
1H-indole
-
-
2,2-diethoxy-N-[(6-methoxy-1,4-dimethyl-9H-carbazol-3-yl)methyl]ethanamine
-
-
2,2-diethoxy-N-[(7-fluoro-1,4-dimethyl-9H-carbazol-3-yl)methyl]ethanamine
-
-
2,2-diethoxy-N-[(8-ethyl-1,4-dimethyl-9H-carbazol-3-yl)methyl]ethanamine
-
-
2,5,11-trimethyl-6H-pyrido[4,3-b]carbazol-2-ium iodide
-
-
2-aminoethylphosphonate
-
weak
2-[(1-[[2-amino-6-(2,6-dichlorophenyl)pyrido[2,3-d]pyrimidin-7-yl]amino]ethenyl)amino]propan-2-ol
-
-
2-[(1-[[2-amino-6-(2,6-difluorophenyl)pyrido[2,3-d]pyrimidin-7-yl]amino]ethenyl)amino]propan-2-ol
-
-
2-[(1-[[2-amino-6-(3,5-dichlorophenyl)pyrido[2,3-d]pyrimidin-7-yl]amino]ethenyl)amino]propan-2-ol
-
-
2-[(1-[[2-amino-6-(3,5-difluorophenyl)pyrido[2,3-d]pyrimidin-7-yl]amino]ethenyl)amino]propan-2-ol
-
-
3-(9-methoxy-5,11-dimethyl-6H-pyrido[4,3-b]carbazol-6-yl)propan-1-amine
-
-
3-chloro-2,2-dimethyl-N-[4(trifluoromethyl)phenyl]propanamide
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
3-[(1,6-dichloro-4-methoxyacridin-9-yl)amino]-2-[(diethylamino)methyl]phenol
-
-
3-[(6-chloro-2-methoxyacridin-9-yl)amino]-2-(pyrrolidin-1-ylmethyl)phenol
-
-
3-[(6-chloro-2-methoxyacridin-9-yl)amino]-2-[(4-methylpiperazin-1-yl)methyl]phenol
-
-
3-[(6-chloro-2-methoxyacridin-9-yl)amino]-2-[(diethylamino)methyl]-6-(prop-2-en-1-yl)phenol
-
-
3-[(6-chloro-2-methoxyacridin-9-yl)amino]-2-[(diethylamino)methyl]phenol
-
-
5,11-Dimethyl-6H-pyrido[4,3-b]carbazole
-
-
5,6,11-trimethyl-6H-pyrido[4,3-b]carbazole
-
-
5-bromo-1H-indole
-
-
5-methoxy-1H-indole
-
-
6-(1,3-benzodioxol-5-yl)pyrido[2,3-d]pyrimidine-2,7-diamine
-
-
6-(2,6-dibromophenyl)pyrido[2,3-d]pyrimidine-2,7-diamine
-
-
6-(2,6-dichlorophenyl)-N2-[3-(dimethylamino)propyl]pyrido[2,3-d]pyrimidine-2,7-diamine
-
-
6-(2,6-dichlorophenyl)-N2-[3-(morpholin-4-yl)propyl]pyrido[2,3-d]pyrimidine-2,7-diamine
-
-
6-(2,6-dichlorophenyl)pyrido[2,3-d]pyrimidine-2,7-diamine
-
-
6-(2,6-difluorophenyl)pyrido[2,3-d]pyrimidine-2,7-diamine
-
-
6-(2-chloro-6-fluorophenyl)pyrido[2,3-d]pyrimidine-2,7-diamine
-
-
6-(3,5-dichlorophenyl)pyrido[2,3-d]pyrimidine-2,7-diamine
-
-
6-(3,5-difluorophenyl)pyrido[2,3-d]pyrimidine-2,7-diamine
-
-
6-(3,5-dimethoxyphenyl)-N2-[3-(morpholin-4-yl)propyl]pyrido[2,3-d]pyrimidine-2,7-diamine
-
-
6-(3,5-dimethoxyphenyl)pyrido[2,3-d]pyrimidine-2,7-diamine
-
-
6-bromo-1,4-dimethyl-9H-carbazole
-
-
6-bromo-1,4-dimethyl-9H-carbazole-3-carbaldehyde
-
-
6-chloro-2-methoxy-N-(6-methoxyquinolin-8-yl)acridin-9-amine
-
-
6-fluoro-1H-indole
-
-
6-methoxy-1,4-dimethyl-9H-carbazole
-
-
6-methoxy-1,4-dimethyl-9H-carbazole-3-carbaldehyde
-
-
6-phenylpyrido[2,3-d]pyrimidine-2,7-diamine
-
-
6-[3,5-bis(trifluoromethyl)phenyl]pyrido[2,3-d]pyrimidine-2,7-diamine
-
-
7-ethyl-1H-indole
-
-
7-ethyl-5,11-dimethyl-6H-pyrido[4,3-b]carbazole
-
-
7-fluoro-1,4-dimethyl-9H-carbazole
-
-
7-fluoro-1,4-dimethyl-9H-carbazole-3-carbaldehyde
-
-
8-ethyl-1,4-dimethyl-9H-carbazole
-
-
8-ethyl-1,4-dimethyl-9H-carbazole-3-carbaldehyde
-
-
8-fluoro-2,5,11-trimethyl-6H-pyrido[4,3-b]carbazol-2-ium iodide
-
-
8-fluoro-5,11-dimethyl-6H-pyrido[4,3-b]carbazole
-
-
8-fluoro-5,6,11-trimethyl-6H-pyrido[4,3-b]carbazole
-
-
9-bromo-2,5,11-trimethyl-6H-pyrido[4,3-b]carbazol-2-ium iodide
-
-
9-bromo-2,5,6,11-tetramethyl-6H-pyrido[4,3-b]carbazol-2-ium iodide
-
-
9-bromo-5,11-dimethyl-6H-pyrido[4,3-b]carbazole
-
-
9-bromo-5,6,11-trimethyl-6H-pyrido[4,3-b]carbazole
-
-
9-methoxy-2,5,11-trimethyl-6H-pyrido[4,3-b]carbazol-2-ium acetate
-
-
9-methoxy-2,5,11-trimethyl-6H-pyrido[4,3-b]carbazol-2-ium iodide
-
-
9-methoxy-2,5,6,11-tetramethyl-6H-pyrido[4,3-b]carbazol-2-ium iodide
-
-
9-methoxy-5,11-dimethyl-6H-pyrido[4,3-b]carbazole
-
-
9-methoxy-5,6,11-trimethyl-6H-pyrido[4,3-b]carbazole
-
-
alpha-Aminophosphonamidic acid
-
time-dependent inhibition in presence of ATP
Aminoalkylphosphinate
-
-
-
apigenin
D-(1-Aminoethyl)phosphinic acid
-
competitive
D-(1-Aminoethyl)phosphonic acid
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
-
D-Ala-D-Ala
-
-
D-Ala-D-Ala phosphinate
-
D-alanyl-D-alanine
-
-
D-cycloserine
diazenocarboxamide
-
dipeptides
EDTA
10 mM, complete inhibition
Gly-Gly
-
-
H-1004
slight inhibition
leflunomide
an antirheumatic drug
LFM-A12
an analog of the Leflunomide metabolite A771726
LFM-A13
Brutons's tyrosine kinase inhibitor, an analog of the Leflunomide metabolite A771726
LY294002
slight inhibition
methylphosphinophosphate
-
strong inhibition
-
N-(2,5-dibromophenyl)-2-oxopropanamide
-
N-[(1,4-dimethyl-9H-carbazol-3-yl)methyl]-2,2-diethoxyethanamine
-
-
N-[(3-chloro-8-methoxy-11H-indolo[3,2-c]quinolin-9-yl)methyl]-N-ethylethanamine
-
-
N-[(6-bromo-1,4-dimethyl-9H-carbazol-3-yl)methyl]-2,2-diethoxyethanamine
-
-
Phosphinates
Phosphonate dipeptide analogs
piceatannol
slight inhibition
quercetin
Tabtoxinine
-
no inhibition by the lactam analogues
tyrphostin 47
competitive versus ATP
tyrphostin 51
mixed-type inhibition
Wortmannin
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
-
additional information
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
A771726
a leflunomide metabolite, slightly activating
N-(2,5-dibromophenyl)-2-oxopropanamide
slightly activating
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
33
2-aminopentanoate
-
reaction with D-Ala + ATP
3
2-hydroxybutanoate
-
-
8.3
2-hydroxypentanoate
-
-
0.00087 - 69
ATP
0.0012 - 86
D-Ala
0.003 - 1200
D-alanine
11.4
D-lactate
-
-
9
D-Met
-
-
15
D-Norleucine
-
reaction with D-Ala + ATP
6
D-Phe
-
reaction with D-Ala + ATP
56
D-serine
-
-
additional information
additional information
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1.9
ATP
Helicobacter pylori
Q2N4T5
pH 8.0-9.0, 30C
4.92 - 17
D-Ala
1.67 - 48.5
D-alanine
2.6
D-serine
Escherichia coli
-
-
additional information
additional information
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
7.96
ATP
Escherichia coli
-
-
4
1.4 - 1500
D-alanine
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.04
3-chloro-2,2-dimethyl-N-[4(trifluoromethyl)phenyl]propanamide
-
0.031 - 0.1195
apigenin
0.06
D-alanyl-D-alanine
-
-
0.002 - 0.92
D-cycloserine
0.185
LFM-A13
-
1.4
LY294002
-
0.215
N-(2,5-dibromophenyl)-2-oxopropanamide
-
1.8
Olomoucine
-
0.0043 - 0.028
quercetin
0.29
tyrphostin 47
-
additional information
additional information
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.133
(E)-N,N'-bis(2-chloroethyl)diazene-1,2-dicarboxamide
Escherichia coli
-
-
0.123
(E)-N,N'-bis(pyridin-3-ylmethyl)diazene-1,2-dicarboxamide
Escherichia coli
-
-
0.049
(E)-N-(2-chloroethyl)-N'-(4-isopropylphenyl)diazene-1,2-dicarboxamide
Escherichia coli
-
-
0.119
(E)-N-(2-chloroethyl)-N'-(pyridin-2-ylmethyl)diazene-1,2-dicarboxamide
Escherichia coli
-
-
0.236
(E)-N-(2-chloroethyl)-N'-(pyridin-4-ylmethyl)diazene-1,2-dicarboxamide
Escherichia coli
-
-
0.015
(E)-N-(3-chlorophenyl)-N'-(pyridin-3-ylmethyl)diazene-1,2-dicarboxamide
Escherichia coli
-
; pH 8.0, 37C
0.033
(E)-N-(3-chlorophenyl)-N'-(pyridin-4-ylmethyl)diazene-1,2-dicarboxamide
Escherichia coli
-
; pH 8.0, 37C
0.073
(E)-N-(4-fluorophenyl)-N'-(pyridin-4-ylmethyl)diazene-1,2-dicarboxamide
Escherichia coli
-
-
0.025
(E)-N-(4-sec-butylphenyl)-N'-(2-chloroethyl)diazene-1,2-dicarboxamide
Escherichia coli
-
-
0.121
(E)-N-cyclohexyl-N'-(pyridin-4-ylmethyl)diazene-1,2-dicarboxamide
Escherichia coli
-
-
0.111
(E)-N-phenyl-N'-(pyridin-2-ylmethyl)diazene-1,2-dicarboxamide
Escherichia coli
-
-
0.036
(E)-N-phenyl-N'-(pyridin-3-ylmethyl)diazene-1,2-dicarboxamide
Escherichia coli
-
; pH 8.0, 37C
0.106
(E)-N-phenyl-N'-(pyridin-4-ylmethyl)diazene-1,2-dicarboxamide
Escherichia coli
-
-
0.025
(E)-N-[4-(butan-2-yl)phenyl]-N'-(2-chloroethyl)diazene-1,2-dicarboxamide
Escherichia coli
-
pH 8.0, 37C
0.135
1-[4-[(6-chloro-2-methoxyacridin-9-yl)amino]phenyl]-3-(dimethylamino)propan-1-ol
Escherichia coli
-
pH 8.0, 37C
0.046
2,5,11-trimethyl-6H-pyrido[4,3-b]carbazol-2-ium iodide
Escherichia coli
-
pH 8.0, 37C
0.07
3-(9-methoxy-5,11-dimethyl-6H-pyrido[4,3-b]carbazol-6-yl)propan-1-amine
Escherichia coli
-
pH 8.0, 37C
0.119
3-[(1,6-dichloro-4-methoxyacridin-9-yl)amino]-2-[(diethylamino)methyl]phenol
Escherichia coli
-
pH 8.0, 37C
0.102
3-[(6-chloro-2-methoxyacridin-9-yl)amino]-2-(pyrrolidin-1-ylmethyl)phenol
Escherichia coli
-
pH 8.0, 37C
0.162
3-[(6-chloro-2-methoxyacridin-9-yl)amino]-2-[(4-methylpiperazin-1-yl)methyl]phenol
Escherichia coli
-
pH 8.0, 37C
0.161
3-[(6-chloro-2-methoxyacridin-9-yl)amino]-2-[(diethylamino)methyl]-6-(prop-2-en-1-yl)phenol
Escherichia coli
-
pH 8.0, 37C
0.32
3-[(6-chloro-2-methoxyacridin-9-yl)amino]-2-[(diethylamino)methyl]phenol
Escherichia coli
-
pH 8.0, 37C
0.192
5,11-Dimethyl-6H-pyrido[4,3-b]carbazole
Escherichia coli
-
pH 8.0, 37C
0.032 - 0.09
6-chloro-2-methoxy-N-(6-methoxyquinolin-8-yl)acridin-9-amine
0.125
7-ethyl-5,11-dimethyl-6H-pyrido[4,3-b]carbazole
Escherichia coli
-
pH 8.0, 37C
0.064
8-fluoro-2,5,11-trimethyl-6H-pyrido[4,3-b]carbazol-2-ium iodide
Escherichia coli
-
pH 8.0, 37C
0.103
8-fluoro-5,11-dimethyl-6H-pyrido[4,3-b]carbazole
Escherichia coli
-
pH 8.0, 37C
0.09
8-fluoro-5,6,11-trimethyl-6H-pyrido[4,3-b]carbazole
Escherichia coli
-
pH 8.0, 37C
0.023
9-bromo-2,5,11-trimethyl-6H-pyrido[4,3-b]carbazol-2-ium iodide
Escherichia coli
-
pH 8.0, 37C
0.036
9-bromo-2,5,6,11-tetramethyl-6H-pyrido[4,3-b]carbazol-2-ium iodide
Escherichia coli
-
pH 8.0, 37C
0.086
9-bromo-5,11-dimethyl-6H-pyrido[4,3-b]carbazole
Escherichia coli
-
pH 8.0, 37C
0.297
9-bromo-5,6,11-trimethyl-6H-pyrido[4,3-b]carbazole
Escherichia coli
-
pH 8.0, 37C
0.089
9-methoxy-2,5,11-trimethyl-6H-pyrido[4,3-b]carbazol-2-ium acetate
Escherichia coli
-
pH 8.0, 37C
0.065
9-methoxy-2,5,11-trimethyl-6H-pyrido[4,3-b]carbazol-2-ium iodide
Escherichia coli
-
pH 8.0, 37C
0.043
9-methoxy-2,5,6,11-tetramethyl-6H-pyrido[4,3-b]carbazol-2-ium iodide
Escherichia coli
-
pH 8.0, 37C
0.06
9-methoxy-5,11-dimethyl-6H-pyrido[4,3-b]carbazole
Escherichia coli
-
pH 8.0, 37C
0.184
9-methoxy-5,6,11-trimethyl-6H-pyrido[4,3-b]carbazole
Escherichia coli
-
pH 8.0, 37C
0.1327 - 0.163
apigenin
0.37
D-cycloserine
Mycobacterium tuberculosis
P9WP31
pH not specified in the publication, temperature not specified in the publication
0.33 - 0.623
N-[(3-chloro-8-methoxy-11H-indolo[3,2-c]quinolin-9-yl)methyl]-N-ethylethanamine
0.0199 - 0.0485
quercetin
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.071
substrate beta-alanine, 60C
0.12
substrate D-threonine, 60C
0.19
-
mutant S137F/Y207F, substrates D-Ala + D-lactate, 60C, pH 7.5
0.2
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
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
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
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
31
-
ligase B
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.2
-
assay at
8
-
assay at
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6 - 9.2
-
higher DDL activity at pH 9.2 than at pH 6.0-7.5
additional information
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
30 - 70
30C: about 70% of maximal activity, 70C: about 50% of maximal activity
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
PDB
SCOP
CATH
ORGANISM
UNIPROT
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)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Leuconostoc mesenteroides subsp. mesenteroides (strain ATCC 8293 / NCDO 523)
Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
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 KACC10331 / KXO85)
Xanthomonas oryzae pv. oryzae (strain MAFF 311018)
Xanthomonas oryzae pv. oryzae (strain MAFF 311018)
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
Crystallization/COMMENTARY
ORGANISM
UNIPROT
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
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
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
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
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
apo, ADP-bound, ATP-bound, and AMPPNP-bound enzyme, sitting drop vapor diffusion method, mixing of 0.0025 ml of protein solution with 00.0025 ml of reservoir solution containing 15% w/v PEG 4000, 0.1 M Tris, pH 8.5, and 0.2 M MgCl2 with 0.3 M dimethylethyl-(3-sulfopropyl)-ammonium, 14C, 24 h, ligand-bound enzyme structures by soaking apoenzyme crystals in each nucleotide-containing reservoir solution, X-ray diffraction structure determination and analysis at 2.0-2.3 A resolution, molecular replacement
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
90
15 min, stable up to
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
recombinant Ddl
-
recombinant His-tagged enzyme from Escherichia coli strain BL21(DE3) by nickel affinity chromatography
-
recombinant His-tagged wild-type and mutant enzymes from Escherichia coli strain BL21(DE3)
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
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 ATM697 and ATM718 as a fusion protein MurC-Ddl
-
expressed in Escherichia coli BL21
-
expression in Escherichia coli
expression in Escherichia coli BL21
expression of N-terminally His-tagged enzyme in Escherichia coli strain BL21(DE3), subcloning in Escherichia coli strain JM109
-
expression of N-terminally His-tagged wild-type and mutant enzymes in Escherichia coli strain BL21(DE3)
overexpression of Ddl in Mycobacterium smegmatis
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
placed under the control of the lac and lambdaPl promoter
-
subcloned behind the tac promoter in the plasmid pKK223-3, expression in Escherichia coli JM105
-
Van B ligase is overproduced in Escherichia coli HB101 harboring recombinant plasmid pAT204
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
presence of transcriptional coupling between ddlB gene associated with peptidoglycan biosynthesis and the fts genes required to control cell division
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
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
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
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
site-directed mutagenesis of an active site mutant, mutant kinetics compared to the wild-type structure
L241F
site-directed mutagenesis of an active site mutant, mutant kinetics compared to the wild-type structure
L241Y
site-directed mutagenesis of an active site mutant, mutant kinetics compared to the wild-type structure
L308T
site-directed mutagenesis of an active site mutant, mutant kinetics compared to the wild-type structure
Y311S
site-directed mutagenesis of an active site mutant, mutant kinetics compared to the wild-type structure
F261Y
-
mutation of the Omega loop, inactive mutant
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
-
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
-
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
-
additional information
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
analysis
drug development
synthesis
-
D-alanine-D-alanine ligase is a biocatalyst for synthesizing D-amino acid dipeptides, use of a thermostable ATP regeneration system
Show AA Sequence (12914 entries)
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