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Information on EC 3.4.16.4 - serine-type D-Ala-D-Ala carboxypeptidase and Organism(s) Actinomadura sp. and UniProt Accession P39045

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Actinomadura sp.
UNIPROT: P39045 not found.
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The taxonomic range for the selected organisms is: Actinomadura sp.
The enzyme appears in selected viruses and cellular organisms
Reaction Schemes
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Preferential cleavage: (Ac)2-L-Lys-D-Ala-/-D-Ala. Also transpeptidation of peptidyl-alanyl moieties that are N-acyl substituents of D-alanine
Synonyms
transpeptidase, penicillin-binding protein, pbp2x, pbp1a, pbp1b, penicillin binding proteins, pbp 2, pbp 3, pbp 5, dd-peptidase, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
carboxypeptidase I
-
-
-
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CPase
-
-
-
-
D-alanine carboxypeptidase
-
-
-
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D-alanine carboxypeptidase I
-
-
-
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D-alanyl carboxypeptidase
-
-
-
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D-alanyl-D-alanine carboxypeptidase
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-
-
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D-Alanyl-D-alanine hydrolase
-
-
-
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D-alanyl-D-alanine peptidase
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-
-
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D-alanyl-D-alanine-carboxypeptidase
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-
-
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D-alanyl-D-alanine-cleaving peptidase
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-
-
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D-alanyl-D-alanine-cleaving-peptidase
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-
-
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DD-Carboxypeptidase
-
-
-
-
DD-peptidase
DD-transpeptidase
-
-
-
-
PBP-5*
-
-
-
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PBP-6B
-
-
-
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PBP5
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-
-
-
penicillin binding protein 5
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-
-
-
penicillin-binding protein
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VanX
-
-
-
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VanY
-
-
-
-
PATHWAY SOURCE
PATHWAYS
-
-, -, -
CAS REGISTRY NUMBER
COMMENTARY hide
9077-67-2
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
3-carboxyphenyl (2R)-N-(phenylacetyl)-2-hydroxyglycinate + H2O
(2R)-N-(phenylacetyl)-2-hydroxyglycine + 3-hydroxybenzoate
show the reaction diagram
no reaction with (S)-enantiomer
substrate for both beta-lactamases and D,D-peptidases. Both prefer the same enantiomer, the (R)-form
-
?
3-carboxyphenyl (2R)-N-(phenylacetyl)-2-methoxyglycinate
(2R)-N-(phenylacetyl)-2-methoxyglycine + 3-hydroxybenzoate
show the reaction diagram
no reaction with (S)-enantiomer
substrate for both beta-lactamases and D,D-peptidases. Both prefer the same enantiomer, the (R)-form
-
?
Nalpha,Nepsilon-diacetyl-L-Lys-D-Ala-D-Ala + H2O
Nalpha,Nepsilon-diacetyl-L-Lys-D-Ala + D-alanine
show the reaction diagram
-
-
-
-
?
Nalpha,Nepsilon-diacetyl-L-lysyl-D-alanyl-D-alanine + H2O
D-alanine + Nalpha,Nepsilon-diacetyl-L-lysyl-D-alanine
show the reaction diagram
-
-
-
-
?
UDP-N-acetyl-muramyl-L-alanyl-D-glutamyl-mesodiaminopimelyl-D-alanyl-D-alanine
?
show the reaction diagram
-
-
-
-
?
UDP-N-acetylmuramoyl-L-alanyl-D-glutamyl-mesodiaminopimelyl-D-alanyl-D-alanine + H2O
UDP-N-acetylmuramoyl-L-alanyl-D-glutamyl-mesodiaminopimelyl-D-alanine + D-alanine
show the reaction diagram
-
-
-
-
?
additional information
?
-
-
requirement for D-Ala in P1 position
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
UDP-N-acetyl-muramyl-L-alanyl-D-glutamyl-mesodiaminopimelyl-D-alanyl-D-alanine
?
show the reaction diagram
-
-
-
-
?
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(2R)-2-amino-7-oxo-7-[(4,4,4-trifluoro-3-oxobutan-2-yl)amino]heptanoic acid
i.e. D-alpha-aminopimelyl-(1,1,1-trifluoro-3-amino)butan-2-one
arylalkylidene rhodanine derivative 2
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95% inhibition
benzylpenicillin
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ester-linked to serins
beta-lactam
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R39 has a high beta-lactam binding activity
beta-lactams
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kinetic constants
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nocardicin A
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-
Oxyimino-DELTA3-cephalosporins
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syn- and anti-isomers
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penicillin
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kinetic model of interaction
penicillin G
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100% inhibition
sulfazecine
-
-
additional information
-
no significant inhibition by arylalkylidene rhodanine derivative 1 and 3 respectively and arylakylidene imino-thiazolidin-4-ones 6, 8, 13, 16, 17 and 19 respectively
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
4.3
3-carboxyphenyl (2R)-N-(phenylacetyl)-2-hydroxyglycinate
pH 7.5, 25°C
0.2
3-carboxyphenyl (2R)-N-(phenylacetyl)-2-methoxyglycinate
pH 7.5, 25°C
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
10.4
3-carboxyphenyl (2R)-N-(phenylacetyl)-2-hydroxyglycinate
pH 7.5, 25°C
114
3-carboxyphenyl (2R)-N-(phenylacetyl)-2-methoxyglycinate
pH 7.5, 25°C
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
24
3-carboxyphenyl (2R)-N-(phenylacetyl)-2-hydroxyglycinate
pH 7.5, 25°C
570
3-carboxyphenyl (2R)-N-(phenylacetyl)-2-methoxyglycinate
pH 7.5, 25°C
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.00037
(2R)-2-amino-7-oxo-7-[(4,4,4-trifluoro-3-oxobutan-2-yl)amino]heptanoic acid
pH not specified in the publication, temperature not specified in the publication
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6 - 8
-
hydrolysis, value increased by high ionic strength
additional information
-
ratio of hydrolysis/transpeptidation depending on pH
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
by hanging drop vapor diffusion, at 1.8 A and 2.4 A resolution, R39 structure is composed of one penicillin binding domain and two unknown domains, the R39 active site does not undergo a great structural deformation upon beta-lactam binding
-
in complex with inhibitor (2R)-2-amino-7-oxo-7-[(4,4,4-trifluoro-3-oxobutan-2-yl)amino]heptanoic acid. The inhibitor is covalently bonded to the active serine Ser49, the carbonyl carbon is now tetrahedral, and the ketone oxygen occupies the oxyanion hole, defined by the backbone NH groups of Ser49 and Thr413. The D-methyl group is directed into a hydrophobic pocket comprised residues Gly148, Leu 349 and Met414. Branching from the tetrahedral carbon bonded to Ser49Ogamma, the CF3 group occupies the likely position of a leaving group in the tetrahedral intermediate of a peptidase substrate
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Laurent, G.; Durant, F.; Frere, J.M.; Klein, D.; Ghuysen, J.M.
Des-, syn- and anti-oxyimino-delta 3-cephalosporins. Intrinsic reactivity and reaction with RTEM-2 serine beta-lactamase and D-alanyl-D-alanine-cleaving serine and Zn2+-containing peptidases
Biochem. J.
218
933-937
1984
Actinomadura sp., Streptomyces sp.
Manually annotated by BRENDA team
Frere, J.M.; Joris, B.
Penicillin-sensitive enzymes in peptidoglycan biosynthesis
CRC Crit. Rev. Microbiol.
11
299-396
1985
Actinomadura sp., Streptomyces sp.
Manually annotated by BRENDA team
Ghuysen, J.M.; Frere, J.M.; Leyh-Bouille, M.; Nguyen-Disteche, M.; Coyette, J.; Dusart, J.; Charlier, P.; Dive, G.; Lamotte-Brasseur, J.
Bacterial wall peptidoglycan, DD-peptidases and beta-lactam antibiotics
Scand. J. Infect. Dis.
42
17-37
1984
Actinomadura sp., Streptomyces sp.
Manually annotated by BRENDA team
Frere, J.M.; Klein, D.; Kelly, J.A.; Ghuysen, J.M.
Interaction between monobactams and model D-alanyl-D-alanine-cleaving peptidases
FEMS Microbiol. Lett.
21
213-217
1984
Actinomadura sp., Streptomyces sp.
-
Manually annotated by BRENDA team
Duez, C.; Joris, B.; Frere, J.M.; Ghuysen, J.M.
The penicillin-binding site in the exocellular DD-carboxypeptidase-transpeptidase of Actinomadura R39
Biochem. J.
193
83-86
1981
Actinomadura sp.
Manually annotated by BRENDA team
Zervosen, A.; Lu, W.P.; Chen, Z.; White, R.E.; Demuth Jr., T.P.; Frre, J.M.
Interactions between penicillin-binding proteins (PBPs) and two novel classes of PBP inhibitors, arylalkylidene rhodanines and arylalkylidene iminothiazolidin-4-ones
Antimicrob. Agents Chemother.
48
961-969
2004
Actinomadura sp., Escherichia coli, Streptomyces sp. R61
Manually annotated by BRENDA team
Sauvage, E.; Herman, R.; Petrella, S.; Duez, C.; Bouillenne, F.; Frre, J.M.; Charlier, P.
Crystal structure of the Actinomadura R39 DD-peptidase reveals new domains in penicillin-binding proteins
J. Biol. Chem.
280
31249-31256
2005
Actinomadura sp., Escherichia coli
Manually annotated by BRENDA team
Dzhekieva, L.; Adediran, S.A.; Herman, R.; Kerff, F.; Duez, C.; Charlier, P.; Sauvage, E.; Pratt, R.F.
Inhibition of DD-peptidases by a specific trifluoroketone: crystal structure of a complex with the Actinomadura R39 DD-peptidase
Biochemistry
52
2128-2138
2013
Actinomadura sp. (P39045)
Manually annotated by BRENDA team
Pelto, R.B.; Pratt, R.F.
Kinetics and stereochemistry of hydrolysis of an N-(phenylacetyl)-alpha-hydroxyglycine ester catalyzed by serine beta-lactamases and DD-peptidases
Org. Biomol. Chem.
10
7356-7362
2012
Streptomyces sp. (P15555), Actinomadura sp. (P39045)
Manually annotated by BRENDA team