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

for references in articles please use BRENDA:EC6.3.2.4
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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
UDP-N-acetylmuramoyl-pentapeptide biosynthesis I (meso-diaminopimelate containing)
-
-
UDP-N-acetylmuramoyl-pentapeptide biosynthesis II (lysine-containing)
-
-
UDP-N-acetylmuramoyl-pentapeptide biosynthesis III (meso-diaminopimelate containing)
-
-
peptidoglycan biosynthesis
-
-
D-Alanine metabolism
-
-
Peptidoglycan biosynthesis
-
-
Metabolic pathways
-
-
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
-
D5D9X4, D5DWS5, G2RMP7
UniProt
Manually annotated by BRENDA team
Bacillus megaterium ATCC 12872 / QM B1551
-
UniProt
Manually annotated by BRENDA team
-
G2RMP7
UniProt
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
Brevibacillus brevis 47 / JCM 6285 / NBRC 100599
-
UniProt
Manually annotated by BRENDA team
serovar L2
-
-
Manually annotated by BRENDA team
Enterococcus faecalis R / ATCC 8043
-
-
-
Manually annotated by BRENDA team
containing recombinant plasmid pAT214, which expressed the VanA protein
-
-
Manually annotated by BRENDA team
9602
-
-
Manually annotated by BRENDA team
Mycobacterium tuberculosis ATCC 25618 / H37Rv
-
UniProt
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
Thermus thermophilus HB8 / ATCC 27634 / DSM 579
-
UniProt
Manually annotated by BRENDA team
pv. oryzae
UniProt
Manually annotated by BRENDA team
-
UniProt
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
evolution
malfunction
-
inhibition of Ddl prevents bacterial growth
metabolism
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-Ala + NH3
ADP + phosphate + D-AlaNH2
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
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(1-Aminoethyl)boronic acid
-
time-dependent, slow binding
(1E,3Z)-N-(2-carbamimidamidoethyl)-4-(pyridin-3-yl)buta-1,3-diene-1-sulfonamide
-
(2-aminoethyl)phosphonic acid
-
(2E)-3-amino-2-[(E)-(3-hydroxy-4-oxocyclohexa-2,5-dien-1-ylidene)methyl]-3-sulfanylprop-2-enenitrile
-
(2R)-2-aminopropanoyl hydrogen (2-hydroxybutanoyl)phosphonate
-
(2R)-2-[[(1-aminoethyl)(hydroxy)phosphoryl]methyl]nonanoic acid
-
(2S)-2-amino-4-[(3S)-3-hydroxy-2-oxoazetidin-3-yl]butanoic acid
-
(2Z)-2-cyano-3-hydroxy-N-(2,4,6-trimethylphenyl)but-2-enamide
-
(2Z)-2-cyano-3-hydroxy-N-[2-methyl-3,6-bis(trifluoromethyl)phenyl]but-2-enamide
-
(2Z)-2-cyano-3-hydroxy-N-[4-(trifluoromethoxy)phenyl]but-2-enamide
-
(2Z)-2-cyano-N-(2,5-dibromophenyl)-3-hydroxybut-2-enamide
-
(2Z)-2-cyano-N-(2,6-dimethylphenyl)-3-hydroxybut-2-enamide
-
(2Z)-N-(2-chloro-6-methylphenyl)-2-cyano-3-hydroxybut-2-enamide
-
(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
(3Z)-4-cyano-5-(3,6-dibromo-2-methylanilino)-3-hydroxy-5-oxopent-3-enoic acid
-
(4R)-4-amino-1,2-oxazolidin-3-one
-
(E)-2-[[(chloromethyl)amino]acetyl]-N-[(pyridin-2-yl)methyl]diazene-1-carboxamide
-
-
(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
-
-
(E)-N1,N2-bis(2-chloroethyl)diazene-1,2-dicarboxamide
-
(E)-N1,N2-bis[(pyridin-3-yl)methyl]diazene-1,2-dicarboxamide
-
(E)-N1-(2-chloroethyl)-N2-(4-methylphenyl)diazene-1,2-dicarboxamide
-
(E)-N1-(2-chloroethyl)-N2-[(pyridin-4-yl)methyl]diazene-1,2-dicarboxamide
-
(E)-N1-(3-chlorophenyl)-N2-[(pyridin-3-yl)methyl]diazene-1,2-dicarboxamide
-
(E)-N1-(3-chlorophenyl)-N2-[(pyridin-4-yl)methyl]diazene-1,2-dicarboxamide
-
(E)-N1-(4-fluorophenyl)-N2-[(pyridin-4-yl)methyl]diazene-1,2-dicarboxamide
-
(E)-N1-cyclohexyl-N2-[(pyridin-2-yl)methyl]diazene-1,2-dicarboxamide
-
(E)-N1-cyclohexyl-N2-[(pyridin-4-yl)methyl]diazene-1,2-dicarboxamide
-
(E)-N1-phenyl-N2-[(pyridin-3-yl)methyl]diazene-1,2-dicarboxamide
-
(E)-N1-phenyl-N2-[(pyridin-4-yl)methyl]diazene-1,2-dicarboxamide
-
(E)-N1-[4-(butan-2-yl)phenyl]-N2-(2-chloroethyl)diazene-1,2-dicarboxamide
-
1,4-dimethyl-9H-carbazole
-
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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-[(4-fluorocyclohexane-1-sulfonyl)amino]-3-(morpholin-4-yl)propan-2-yl dihydrogen phosphate
-
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-(3,4-dihydroxyphenyl)-3,5,7-trihydroxy-4H-1-benzopyran-4-one
-
2-(3-methylmorpholin-4-yl)-8-phenyl-2,3-dihydro-4H-1-benzopyran-4-one
-
2-([(1R)-1-aminoethyl](hydroxy)phosphoryl]methyl)octanoic acid
-
2-amino-4-(3,4,5-trihydroxyphenyl)but-1-ene-1,1,3-tricarbonitrile
-
2-aminoethylphosphonate
-
weak
2-cyano-3-hydroxy-N-[2-methyl-4-(trifluoromethyl)phenyl]butanamide
-
2-hydroxy-N-(2,4,6-trimethylphenyl)benzamide
-
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
-
-
2-[[(1-aminoethyl)(hydroxy)phosphoryl]methyl]nonanoic acid
-
2-[[6-(benzylamino)-9-methyl-9H-purin-2-yl]amino]ethan-1-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-chloro-2,2-dimethyl-N-[4-(trifluoromethyl)cyclohexyl]propanamide
-
3-chloro-2,2-dimethyl-N-[4-(trifluoromethyl)phenyl]propanamide
-
binding structure, overview
-
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
-
-
3-[[(1S)-1-aminoethyl](hydroxy)phosphoryl]-2-methylpropanoic acid
-
4-chloro-3,3-dimethyl-N-[4-(trifluoromethyl)phenyl]butanamide
-
4-[(E)-2-(3,5-dihydroxyphenyl)ethenyl]benzene-1,2-diol
-
5,11-Dimethyl-6H-pyrido[4,3-b]carbazole
-
-
5,6,11-trimethyl-6H-pyrido[4,3-b]carbazole
-
-
5,7-dihydroxy-2-(4-hydroxyphenyl)-4H-1-benzopyran-4-one
-
5-bromo-1H-indole
-
-
5-methoxy-1H-indole
-
-
5-methyl-N-[4-(trifluoromethyl)phenyl]-1,2-oxazole-4-carboxamide
-
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-(3,5-dimethylphenyl)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-(2,6-dimethylphenyl)-2-hydroxybenzamide
-
N-(2-amino-6-phenylpyrido[2,3-d]pyrimidin-7-yl)-N'-tert-butylurea
-
N-(3,6-dibromo-2-methylphenyl)-2-hydroxybenzamide
-
N-tert-butyl-N'-[6-(2,6-dichlorophenyl)-2-[[3-(morpholin-4-yl)propyl]amino]pyrido[2,3-d]pyrimidin-7-yl]urea
-
N-tert-butyl-N'-[6-(3,5-dimethoxyphenyl)-2-[[3-(morpholin-4-yl)propyl]amino]pyrido[2,3-d]pyrimidin-7-yl]urea
-
N-[(1,4-dimethyl-9H-carbazol-3-yl)methyl]-2,2-diethoxyethanamine
-
-
N-[(2S)-1-[(dihydroxyphosphanyl)oxy]-1-oxopropan-2-yl]-D-alaninamide
-
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
-
-
N-[2-amino-6-(2,6-dibromophenyl)pyrido[2,3-d]pyrimidin-7-yl]-N'-tert-butylurea
-
N-[2-amino-6-(2,6-dichlorophenyl)pyrido[2,3-d]pyrimidin-7-yl]-N'-tert-butylurea
-
N-[2-amino-6-(2,6-difluorophenyl)pyrido[2,3-d]pyrimidin-7-yl]-N'-tert-butylurea
-
N-[2-amino-6-(2-chloro-6-fluorophenyl)pyrido[2,3-d]pyrimidin-7-yl]-N'-tert-butylurea
-
N-[2-amino-6-(3,5-dichlorophenyl)pyrido[2,3-d]pyrimidin-7-yl]-N'-tert-butylurea
-
N-[2-amino-6-(3,5-difluorophenyl)pyrido[2,3-d]pyrimidin-7-yl]-N'-tert-butylurea
-
N-[2-amino-6-(3,5-dimethoxyphenyl)pyrido[2,3-d]pyrimidin-7-yl]-N'-tert-butylurea
-
N-[2-amino-6-[3,5-bis(trifluoromethyl)phenyl]pyrido[2,3-d]pyrimidin-7-yl]-N'-tert-butylurea
-
N2-(3-aminopropyl)-6-(3,5-dimethoxyphenyl)pyrido[2,3-d]pyrimidine-2,7-diamine
-
P-(aminomethyl)phosphonamidic acid
-
Phosphinates
-
phospho-D-cycloserine
-
DCSP, inhibition of D-Ala:D-Ala ligase through a phosphorylated form of the antibiotic D-cycloserine, DCS, bimodal mechanism of action of the inhibitor. The compound also inhibits the phosphatase activity of EcDdlB, formation of phospho-D-cycloserine by EcDdlB in solution a positional isotope exchange (PIX) reaction, a phosphatase activity of EcDdlB is detected as a side-reaction alongside the positional isotope exchange (PIX) reaction. DCS is the specific acceptor of the ATP gamma-P group during the phosphate transfer reaction by the enzyme, and DCS inhibits EcDdlB phosphatase activity
Phosphonate dipeptide analogs
-
phosphorylated D-ala-D-alpha-hydroxybutyrate phosphonate
-
binding structure, overview
-
piceatannol
slight inhibition
quercetin
Tabtoxinine
-
no inhibition by the lactam analogues
tyrphostin 47
competitive versus ATP
tyrphostin 51
mixed-type inhibition
Vancomycin
the antibiotic is primarily used against methicillin-resistant Staphylococcus, it recognizes the terminal D-Ala-D-Ala moiety of the peptide chain of peptidoglycan and inhibits the cross-linking of cell-wall peptidoglycan precursors, eventually causing bacterial cell lysis
Wortmannin
slight inhibition
[(1R)-1-aminoethyl]phosphinic acid
-
[(1R)-1-aminoethyl]phosphonic acid
-
[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
-
-
1530 - 1580
NH3
additional information
additional information
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.00073 - 1.9
ATP
4.92 - 17
D-Ala
0.00073 - 48.5
D-alanine
2.6
D-serine
-
-
additional information
additional information
-
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
7.96
ATP
-
-
0.0103 - 3760.4
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
-
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
7.5
-
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 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
Acinetobacter baumannii (strain ACICU)
Acinetobacter baumannii (strain ACICU)
Burkholderia ambifaria (strain MC40-6)
Burkholderia pseudomallei (strain 1106a)
Burkholderia pseudomallei (strain 1710b)
Burkholderia pseudomallei (strain K96243)
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)
Paraburkholderia xenovorans (strain LB400)
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)
Vibrio cholerae serotype O1 (strain ATCC 39315 / El Tor Inaba N16961)
Xanthomonas oryzae pv. oryzae (strain KACC10331 / KXO85)
Xanthomonas oryzae pv. oryzae (strain KACC10331 / KXO85)
Xanthomonas oryzae pv. oryzae (strain KACC10331 / KXO85)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
38000
-
x * 38000, SDS-PAGE
39271
-
x * 39271, calculation from nucleotide sequence
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
purified recombinant enzyme, development of several different crystallization conditions for the AbDDL protein, e.g. sitting drop vapor diffusion method, 14C, by mixing of 0.06 M MgCl2 and CaCl2, 0.1 M imidazole, 2-(N-morpholino)ethanesulfonic acid-HCl, pH 6.5, with 30% of the precipitant EDO-P8K containing 40% v/v ethylene glycol and 20% w/v PEG 8000, or by microbatch method with 0.2 M NaSCN and 20% w/v PEG 3350 as crystallization solution, X-ray diffraciton structure determination and analysis at 2.2 A resolution, molecular replacement wit the DDL crystal structure from Yestis pestis as a template, PDB ID 3v4z
-
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
-
purified recombinant His-tagged enzyme in complex with ATP and D-alanyl-D-alanine, or with ATD and D-alanyl-D-alanine, or with inhibitor D-cycloserine and ADP, hanging drop method, mixing of 0.002 ml of 12 mg/ml protein in 50 mM HEPES, pH 7.5, 150 mM KCl, 0.5 mM EDTA, 5 mM ATP or 5 mM ADP, and 50 mM D-alanyl-D-alanine, with 0.002 ml of reservoir solution containing 200 mM MgCl2, 25% PEG 3350, 100 mM TrisHCl pH 8.0, 18C, X-ray diffraction structure determination and analysis at 1.4-1.65 A resolution, active site region of EcDdlB in the different complexes, overview
-
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
purified enzyme in apoform, AMP-bound, ADP-bound, adenosine 5'-(beta,gamma-imido)triphosphate-bound, and D-alanyl-D-alanine, and ADP-bound structures, hanging drop vapour diffusion method, mixing of 900 nl of 8 mg/ml protein in 20 mM Tris-HCl, pH 8.0, 20 mM NaCl, and 3 mM 2-mercaptoethanol, with 900 nl of reservoir solution containing 0.2 M sodium acetate, 0.1 M Bis-Tris, pH 7.0, and 29% PEG 8000, and equilibration against 1 ml of reservoir solution, 14C, 2 days, method optimization, X-ray diffraction structure determination and analysis 1.7-2.5 A resolution, molecular replacement of the apoenzyme structure using a structure as model, PDB entry 3v4z
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
90
15 min, stable up to