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Information on EC 5.1.1.1 - alanine racemase and Organism(s) Escherichia coli and UniProt Accession P0A6B4
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5.1.1.1 alanine racemaseIUBMB Comments
A pyridoxal-phosphate protein.
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Word Map
- 5.1.1.1
- pyridoxal
- 5'-phosphate
- peptidoglycan
-
racemization
- d-cycloserine
- stearothermophilus
-
plp-dependent
-
d-amino
-
aldimine
- d-alanyl-d-alanine
- exosporium
-
pyridoxal-5'-phosphate-dependent
- drug development
-
5'-phosphate-dependent
-
d-alanine:d-alanine
- medicine
- biotechnology
- pharmacology
The taxonomic range for the selected organisms is: Escherichia coli
The expected taxonomic range for this enzyme is: Bacteria, Archaea, Eukaryota
The expected taxonomic range for this enzyme is: Bacteria, Archaea, Eukaryota
Synonyms
alanine racemase, alr-2, d-alanine racemase, mbalr2, alrbax, alrtt, alraba, cdalr, l-alanine racemase, cbl/alr, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
ALR
L-Alanine racemase
-
-
-
-
L-Alanine:D-alanine racemase
-
-
-
-
Racemase, alanine
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
racemization
racemization
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
alanine racemase
A pyridoxal-phosphate protein.
CAS REGISTRY NUMBER
COMMENTARY
9024-06-0
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
additional information
?
-
the Escherichia coli cystathionine beta-lyase (CBL, EC 4.4.1.13) also shows a promiscuous alanine racemase (ALR) activity. CBL catalyzes the beta-elimination of cystathionine
-
-
-
additional information
?
-
-
the Escherichia coli cystathionine beta-lyase (CBL, EC 4.4.1.13) also shows a promiscuous alanine racemase (ALR) activity. CBL catalyzes the beta-elimination of cystathionine
-
-
-
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
pyridoxal 5'-phosphate
-
stabilizes anionic intermediate after abstraction of alpha-hydrogen of the substrate amino acid by forming a quinoid intermediate
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
L-Cycloserine
competitive inhibition, importance of N2-structural site in cyloserine for bioactivity
norleucyl-N-[(1R)-1-phosphonoethyl]-L-alaninamide
moderate in vivo activity
norvalyl-N-[(1R)-1-phosphonoethyl]-L-alaninamide
moderate in vivo activity
cycloserine
-
8 microg/ml bacterial culture extract markedly inhibits alanine racemase
D-cycloserine
-
time-dependent inactivation rate of enzyme from Streptomyces lavendulae is slower than for enzyme from Escherichia coli
D-cycloserine
competitive inhibition, importance of N2-structural site in cyloserine for bioactivity
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.304
D-alanine
+/-0.034, Alr P219A, 30°C, pH 8.0, spectrophotometrically measured at 340 nm
0.311
D-alanine
+/-0.008, Alr wildtype, 30°C, pH 8.0, spectrophotometrically measured at 340 nm
0.402
D-alanine
+/-0.055, Alr E221K, 30°C, pH 8.0, spectrophotometrically measured at 340 nm
0.439
D-alanine
+/-0.080, Alr E221A, 30°C, pH 8.0, spectrophotometrically measured at 340 nm
0.513
D-alanine
+/-0.084, Alr E221P, 30°C, pH 8.0, spectrophotometrically measured at 340 nm
0.528
D-alanine
+/-0.079, Alr E165K, 30°C, pH 8.0, spectrophotometrically measured at 340 nm
0.592
D-alanine
+/-0.085, Alr E165A, 30°C, pH 8.0, spectrophotometrically measured at 340 nm
0.604
D-alanine
+/-0.070, Alr D164K, 30°C, pH 8.0, spectrophotometrically measured at 340 nm
0.615
D-alanine
+/-0.032, Alr D164A, 30°C, pH 8.0, spectrophotometrically measured at 340 nm
1.008
D-alanine
+/-0.069, Alr wildtype, 30°C, pH 8.0, spectrophotometrically measured at 340 nm
1.049
L-alanine
+/-0.131, Alr P219A, 30°C, pH 8.0, spectrophotometrically measured at 340 nm
1.401
L-alanine
+/-0.209, Alr E221P, 30°C, pH 8.0, spectrophotometrically measured at 340 nm
1.516
L-alanine
+/-0.083, Alr E221A, 30°C, pH 8.0, spectrophotometrically measured at 340 nm
1.562
L-alanine
+/-0.256, Alr E165A, 30°C, pH 8.0, spectrophotometrically measured at 340 nm
1.993
L-alanine
+/-0.269, Alr E221K, 30°C, pH 8.0, spectrophotometrically measured at 340 nm
2.057
L-alanine
+/-0.038, Alr E165K, 30°C, pH 8.0, spectrophotometrically measured at 340 nm
3.03
L-alanine
+/-0.114, Alr D164A, 30°C, pH 8.0, spectrophotometrically measured at 340 nm
3.603
L-alanine
+/-0.180, Alr D164K, 30°C, pH 8.0, spectrophotometrically measured at 340 nm
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.333
D-alanine
+/-0.033, Alr D164K, 30°C, pH 8.0, spectrophotometrically measured at 340 nm
1.317
D-alanine
+/-0.100, Alr E165K, 30°C, pH 8.0, spectrophotometrically measured at 340 nm
4
D-alanine
+/-0.417, Alr E165A, 30°C, pH 8.0, spectrophotometrically measured at 340 nm
4.466
D-alanine
+/-0.200, Alr D164A, 30°C, pH 8.0, spectrophotometrically measured at 340 nm
5.267
D-alanine
+/-0.333, Alr P219A, 30°C, pH 8.0, spectrophotometrically measured at 340 nm
5.783
D-alanine
+/-0.483, Alr wildtype, 30°C, pH 8.0, spectrophotometrically measured at 340 nm
6.35
D-alanine
+/-0.333, Alr E221K, 30°C, pH 8.0, spectrophotometrically measured at 340 nm
6.817
D-alanine
+/-0.650, Alr E221A, 30°C, pH 8.0, spectrophotometrically measured at 340 nm
7.617
D-alanine
+/-0.750, Alr E221P, 30°C, pH 8.0, spectrophotometrically measured at 340 nm
2.8
L-alanine
+/-0.250, Alr D164K, 30°C, pH 8.0, spectrophotometrically measured at 340 nm
16.72
L-alanine
+/-0.850, Alr E165K, 30°C, pH 8.0, spectrophotometrically measured at 340 nm
22.47
L-alanine
+/-2.667, Alr E165A, 30°C, pH 8.0, spectrophotometrically measured at 340 nm
41.82
L-alanine
+/-2.600, Alr D164A, 30°C, pH 8.0, spectrophotometrically measured at 340 nm
51.77
L-alanine
+/-6.067, Alr P219A, 30°C, pH 8.0, spectrophotometrically measured at 340 nm
53.98
L-alanine
+/-3.217, Alr wildtype, 30°C, pH 8.0, spectrophotometrically measured at 340 nm
67.07
L-alanine
+/-7.633, Alr E221P, 30°C, pH 8.0, spectrophotometrically measured at 340 nm
68.23
L-alanine
+/-7.550, Alr E221K, 30°C, pH 8.0, spectrophotometrically measured at 340 nm
70.92
L-alanine
+/-2.333, Alr E221A, 30°C, pH 8.0, spectrophotometrically measured at 340 nm
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
assay method based on circular dichroism spectra of D- and L-alanine
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
alanine racemase is a fold type III pyridoxal 5'-phosphate-dependent amino acid racemase enzyme
physiological function
D-alanine, produced by the action of alanine racemase on L-alanine, is important to both Gram-positive and Gram-negative bacteria, since it is required for the synthesis of the peptidoglycan in the cell wall
evolution
several bacteria with reduced genomes lack alr, encoding alanine racemase, but contain metC encoding cystathionine beta-lyase (CBL, EC 4.4.1.13), which, in these organisms, is a multifunctional CBL/ALR. CBL activity is no longer required in these bacteria. Primordial-like enzymes may be an essential part of the adaptive strategy associated with streamlining
metabolism
additional information
metabolism
several bacteria with reduced genomes lack alr, encoding alanine racemase, but contain metC encoding cystathionine beta-lyase (CBL, EC 4.4.1.13), which, in these organisms, is a multifunctional CBL/ALR. CBL activity is no longer required in these bacteria
additional information
comparisons of structure and function of CBL and ALR, overview
additional information
-
comparisons of structure and function of CBL and ALR, overview
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
homodimer
tetramer
the Escherichia coli CBL tetramer (PDB entry 1CL1) adopts fold type I
dimer
the Escherichia coli ALR dimer (PDB entry 2RJG) adopts a fold type III
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
D164A
alanine racemase Alr from Escherichia coli with single point mutation from D to A at position 164
D164K
alanine racemase Alr from Escherichia coli with single point mutation from D to K at position 164
E165A
alanine racemase Alr from Escherichia coli with single point mutation from E to A at position 165
E165K
alanine racemase Alr from Escherichia coli with single point mutation from E to K at position 165
E221A
alanine racemase Alr from Escherichia coli with single point mutation from E to A at position 221
E221K
alanine racemase Alr from Escherichia coli with single point mutation from E to K at position 221
E221P
alanine racemase Alr from Escherichia coli with single point mutation from E to P at position 221
P219A
alanine racemase Alr from Escherichia coli with single point mutation from P to A at position 219
additional information
-
DNA shuffling of enzyme genes from Salmonella typhimurium and Escherichia coli selecting clones that exhibit higher catalytic activity toward alanine as well as serine. Specific activities of selected clones were increased up to three times more than of wild types. One mutant achieves posttranslationally a high protein level
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
Escherichia coli strain BL21 (DE3) was transformed with pET28aAlr (1 wild-type and 8 single point mutants)
gene metC, phylogenetic analysis. The recombinant enzyme EcCBL is overexpressed in a metC-deficient DELTAmetC Escherichia coli mutant strain and can complement it partially
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
drug development
Alr is a target for the development of antibacterial drugs
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Walsh, C.T.
Enzymes in the D-alanine branch of bacterial cell wall peptidoglycan assembly
J. Biol. Chem.
264
2393-2396
1989
Geobacillus stearothermophilus, Escherichia coli, Salmonella enterica subsp. enterica serovar Typhimurium, Staphylococcus sp.
Thornberry, N.A.; Bull, H.G.; Taub, D.; Greenlee, W.J.; Patchett, A.A.; Cordes, E.H.
Halovinylglycines. Efficient irreversible inhibitors of E. coli alanine racemase
J. Am. Chem. Soc.
109
7543-7544
1987
Escherichia coli
-
Thornberry, N.A.; Bull, H.G.; Taub, D.; Wilson, K.E.; Gimenez-Gallego, G.; Rosegay, A.; Soderman, D.D.; Patchett, A.A.
Mechanism-based inactivation of alanine racemase by 3-halovinylglycines
J. Biol. Chem.
266
21657-21665
1991
Escherichia coli, Escherichia coli B / ATCC 11303
Zboinska, E.; Sztajer, H.; Lejczak, B.; Kafarski, P.
Antibacterial activity of phosphono dipeptides based on 1-amino-1-methylethanephosphonic acid
FEMS Microbiol. Lett.
58
23-28
1990
Escherichia coli, Serratia marcescens
Noda, M.; Matoba, Y.; Kumagai, T.; Sugiyama, M.
A novel assay method for an amino acid racemase reaction based on circular dichroism
Biochem. J.
389
491-496
2005
Streptomyces lavendulae, Escherichia coli
Noda, M.; Kawahara, Y.; Ichikawa, A.; Matoba, Y.; Matsuo, H.; Lee, D.G.; Kumagai, T.; Sugiyama, M.
Self-protection mechanism in D-cycloserine-producing Streptomyces lavendulae. Gene cloning, characterization, and kinetics of its alanine racemase and D-alanyl-D-alanine ligase, which are target enzymes of D-cycloserine
J. Biol. Chem.
279
46143-46152
2004
Escherichia coli, Streptomyces lavendulae (Q65YW7), Streptomyces lavendulae
Ju, J.; Misono, H.; Ohnishi, K.
Directed evolution of bacterial alanine racemases with higher expression level
J. Biosci. Bioeng.
100
246-254
2005
Escherichia coli, Salmonella enterica subsp. enterica serovar Typhimurium
Yoshimura, T.; Goto, M.
D-amino acids in the brain: structure and function of pyridoxal phosphate-dependent amino acid racemases
FEBS J.
275
3527-3537
2008
Bacillus subtilis, Bipolaris zeicola, Escherichia coli, Salmonella enterica subsp. enterica serovar Typhimurium, Tolypocladium inflatum, Geobacillus stearothermophilus (P10724)
Wu, D.; Hu, T.; Zhang, L.; Chen, J.; Du, J.; Ding, J.; Jiang, H.; Shen, X.
Residues Asp164 and Glu165 at the substrate entryway function potently in substrate orientation of alanine racemase from Escherichia coli: Enzymatic characterization with crystal structure analysis
Protein Sci.
17
1066-1076
2008
Escherichia coli (P0A6B4), Escherichia coli
Jamindar, D.; Gutheil, W.G.
A liquid chromatography-tandem mass spectrometry assay for Marfeys derivatives of L-Ala, D-Ala, and D-Ala-D-Ala: application to the in vivo confirmation of alanine racemase as the target of cycloserine in Escherichia coli
Anal. Biochem.
396
1-7
2010
Escherichia coli
Priyadarshi, A.; Lee, E.H.; Sung, M.W.; Nam, K.H.; Lee, W.H.; Kim, E.E.; Hwang, K.Y.
Structural insights into the alanine racemase from Enterococcus faecalis
Biochim. Biophys. Acta
1794
1030-1040
2009
Escherichia coli (P0A6B4), Geobacillus stearothermophilus (P10724), Haemophilus influenzae (P45257), Mycobacterium tuberculosis (P9WQA9), Helicobacter pylori (Q1XG01), Enterococcus faecalis v583 (Q837J0), Enterococcus faecalis v583, Pseudomonas aeruginosa (Q9HTQ2), Mycobacterium tuberculosis H37Rv (P9WQA9)
Ju, J.; Xu, S.; Furukawa, Y.; Zhang, Y.; Misono, H.; Minamino, T.; Namba, K.; Zhao, B.; Ohnishi, K.
Correlation between catalytic activity and monomer-dimer equilibrium of bacterial alanine racemases
J. Biochem.
149
83-89
2011
Escherichia coli, Pseudomonas aeruginosa, Pseudomonas fluorescens, Pseudomonas fluorescens LRB3W1, Pseudomonas fluorescens TM5-2, Pseudomonas putida, Pseudomonas putida KT 2240, Salmonella enterica subsp. enterica serovar Typhimurium
Azam, M.A.; Jayaram, U.
Inhibitors of alanine racemase enzyme a review
J. Enzyme Inhib. Med. Chem.
31
517-526
2016
Geobacillus stearothermophilus, Bacillus cereus, Chlamydia pneumoniae, Enterobacter sp., Enterococcus faecalis, Lactiplantibacillus plantarum, Lactococcus lactis, Listeria monocytogenes, Methanococcus maripaludis, Staphylococcus aureus, Mycobacterium tuberculosis, Mycolicibacterium smegmatis, no activity in Homo sapiens, Proteus mirabilis, Salmonella enterica subsp. enterica serovar Typhimurium, Serratia marcescens, Erysipelothrix rhusiopathiae, Escherichia coli (P0A6B4), Pseudomonas aeruginosa (Q9HUN4), Pseudomonas aeruginosa ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C / PRS 101 / PAO1 (Q9HUN4)
Ferla, M.P.; Brewster, J.L.; Hall, K.R.; Evans, G.B.; Patrick, W.M.
Primordial-like enzymes from bacteria with reduced genomes
Mol. Microbiol.
105
508-524
2017
Candidatus Pelagibacter ubique (Q4FME3), Candidatus Pelagibacter ubique, Candidatus Pelagibacter ubique HTCC1062 (Q4FME3), Escherichia coli (P06721), Escherichia coli, Thermotoga maritima (Q9X0Z7), Thermotoga maritima, Thermotoga maritima ATCC 43589 (Q9X0Z7), Thermotoga maritima DSM 3109 (Q9X0Z7), Thermotoga maritima JCM 10099 (Q9X0Z7), Wolbachia pipientis (Q73GL9), Wolbachia pipientis wMel (Q73GL9)
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