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Information on EC 5.1.1.1 - alanine racemase and Organism(s) Pseudomonas aeruginosa

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EC Tree
     5 Isomerases
         5.1 Racemases and epimerases
             5.1.1 Acting on amino acids and derivatives
                5.1.1.1 alanine racemase
IUBMB Comments
A pyridoxal-phosphate protein.
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This record set is specific for:
Pseudomonas aeruginosa
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Word Map
The taxonomic range for the selected organisms is: Pseudomonas aeruginosa
The expected taxonomic range for this enzyme is: Bacteria, Archaea, Eukaryota
Reaction Schemes
Synonyms
alanine racemase, alr-2, d-alanine racemase, alrbax, mbalr2, alrtt, alraba, cdalr, l-alanine racemase, ecalr, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
alanine racemase
-
L-Alanine racemase
-
-
-
-
L-Alanine:D-alanine racemase
-
-
-
-
Racemase, alanine
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
racemization
-
-
-
-
PATHWAY SOURCE
PATHWAYS
-
-, -, -, -
SYSTEMATIC NAME
IUBMB Comments
alanine racemase
A pyridoxal-phosphate protein.
CAS REGISTRY NUMBER
COMMENTARY hide
9024-06-0
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
D-alanine
L-alanine
show the reaction diagram
-
-
-
-
r
L-Ala
D-Ala
show the reaction diagram
L-alanine
D-alanine
show the reaction diagram
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
L-Ala
D-Ala
show the reaction diagram
-
enzyme is required for production of D-Ala, a necessary component of the bacterial cell wall
-
?
L-alanine
D-alanine
show the reaction diagram
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
pyridoxal 5'-phosphate
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
((6R)-2-carboxy-8-oxo-7-[2-(thiophen-2-yl)acetamido]-5-thia-1-azabicyclo[4.2.0]oct-2-en-3-yl)methyl 3-chloro-D-alanyl-D-alaninate
-
(2S)-1-oxo-1-([(1R)-1-phosphonoethyl]amino)propan-2-yl L-methioninate
-
3-halovinylglycine
-
alafosfalin
selective inhibitor of peptidoglycan biosynthesis in both Grampositive and Gram-negative bacteria
beta-Chloro-D-alanine
90-95% inhibition
beta-chloro-L-alanine
-
D-cycloserine
competitive inhibition, importance of N2-structural site in cyloserine for bioactivity
L-Cycloserine
competitive inhibition, importance of N2-structural site in cyloserine for bioactivity
L-leucyl-N-[(1R)-1-phosphonoethyl]-L-alaninamide
-
L-norvalyl-L-chlorovinylglycine
-
O-carbamoyl-D-serine
-
Vinylglycine
-
-
[(1R)-1-amino-2-chloroethyl]phosphonic acid
-
additional information
N2-substitution of carboxybenzyl-protected derivatives of DL-cycloserine proceed smoothly with the requisite alkyl halide in the presence of potassium tert-butoxide in dimethylformamide. The synthesised compounds are evaluated for their inhibitory activity against purified Alrs (Alr gene product). Structural modification at the N2 position result in reduced activity in the enzyme assay and underscore the importance of structural modification at N2-position of cycloserine. A compound with CH2CONHOCH3 substituent at (N)-2 position exhibits modest inhibitory activity against purified Alr enzyme from Escherichia coli, Ki is 0.47 mM. No inhibition by ((6R)-2-carboxy-8-oxo-7-[2-(thiophen-2-yl)acetamido]-5-thia-1-azabicyclo[4.2.0]oct-2-en-3-yl)methyl 3-chloro-D-alanyl-3-chloro-D-alaninate
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1.1 - 1.4
D-Ala
4.2 - 5.6
D-alanine
1.1 - 1.4
L-Ala
4.1 - 9.8
L-alanine
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0138
D-cycloserine
pH and temperature not specified in the publication
0.0138
L-Cycloserine
pH and temperature not specified in the publication
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
evolution
alanine racemase is a fold type III pyridoxal 5'-phosphate-dependent amino acid racemase enzyme. Pseudomonas aeruginosa has two isozymes, encoded by the Alr and the DadB genes
metabolism
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
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
A0A643EDL7_PSEAI
357
0
38953
TrEMBL
-
A0A8G7D9U5_PSEAI
358
0
38299
TrEMBL
-
A0A509JCB1_PSEAI
357
0
39097
TrEMBL
-
A0A8G3ASV5_PSEAI
358
0
38326
TrEMBL
-
A0A6B1YB29_PSEAI
357
0
38945
TrEMBL
-
A0A8F9KBU1_PSEAI
357
0
38974
TrEMBL
-
A0A2R3INB0_PSEAI
363
0
39017
TrEMBL
-
A0A8G2ZDV3_PSEAI
358
0
38373
TrEMBL
-
A0A485H893_PSEAI
116
0
12683
TrEMBL
-
A0A367MA98_PSEAI
358
0
38382
TrEMBL
-
A0A509JIV9_PSEAI
363
0
38745
TrEMBL
-
A0A8G2KUJ1_PSEAI
357
0
38970
TrEMBL
-
A0A2R3J187_PSEAI
357
0
38892
TrEMBL
-
A0A8G2S131_PSEAI
358
0
38504
TrEMBL
-
A0A072ZWM5_PSEAI
358
0
38354
TrEMBL
-
A0A8F9JXD0_PSEAI
358
0
38427
TrEMBL
-
A0A485H636_PSEAI
57
0
6124
TrEMBL
-
A0A8G5EUC4_PSEAI
357
0
39012
TrEMBL
-
A0A8G2KE96_PSEAI
357
0
39002
TrEMBL
-
A0A8G6DTH0_PSEAI
360
0
38468
TrEMBL
-
A0A367M8S8_PSEAI
176
0
18968
TrEMBL
-
A0A8G2N6L6_PSEAI
357
0
39012
TrEMBL
-
A0A8G4AFA5_PSEAI
358
0
38366
TrEMBL
-
A0A8G4DJM2_PSEAI
357
0
39028
TrEMBL
-
A0A8G7I1S0_PSEAI
358
0
38451
TrEMBL
-
A0A3M5DAJ1_PSEAI
360
0
38594
TrEMBL
-
A0A485GRJ3_PSEAI
358
0
38571
TrEMBL
-
A0A8F9NXU8_PSEAI
357
0
38965
TrEMBL
-
A0A8G6G283_PSEAI
333
0
35625
TrEMBL
-
A0A0A8RKE1_PSEAI
368
0
40215
TrEMBL
-
A0A8G5CTS8_PSEAI
358
0
38535
TrEMBL
-
A0A8G3ZT38_PSEAI
358
0
38269
TrEMBL
-
A0A8G3PH41_PSEAI
360
0
38611
TrEMBL
-
A0A8G7FPJ5_PSEAI
358
0
38412
TrEMBL
-
A0A3N0EMU8_PSEAI
357
0
39058
TrEMBL
-
A0A8G7CP04_PSEAI
358
0
38507
TrEMBL
-
A0A8G6G138_PSEAI
357
0
38901
TrEMBL
-
A0A8G5IX33_PSEAI
357
0
39040
TrEMBL
-
A0A8G6A828_PSEAI
363
0
38814
TrEMBL
-
A0A7M3B2X2_PSEAI
358
0
38463
TrEMBL
-
A0A8G4JXB9_PSEAI
358
0
38328
TrEMBL
-
A0A485H8A3_PSEAI
105
0
11699
TrEMBL
-
A0A8B5BKP5_PSEAI
358
0
38382
TrEMBL
-
A0A232BI16_PSEAI
357
0
38915
TrEMBL
-
A0A8G2PX96_PSEAI
358
0
38311
TrEMBL
-
A0A8G4GYD6_PSEAI
357
0
38957
TrEMBL
-
A0A8G4NBD6_PSEAI
357
0
38939
TrEMBL
-
A0A0F6RVW7_PSEAI
358
0
38368
TrEMBL
-
A0A8G6Y1R5_PSEAI
358
0
38301
TrEMBL
-
A0A659BEA5_PSEAI
357
0
38960
TrEMBL
-
A0A8G6ICA9_PSEAI
357
0
39086
TrEMBL
-
A0A8G2NSF3_PSEAI
357
0
38994
TrEMBL
-
A0A485GC23_PSEAI
357
0
38878
TrEMBL
-
A0A8G6DKK3_PSEAI
358
0
38315
TrEMBL
-
A0A8G6R0K2_PSEAI
358
0
38326
TrEMBL
-
A0A8G4AJA3_PSEAI
363
0
38784
TrEMBL
-
A0A8G2S4E3_PSEAI
357
0
38993
TrEMBL
-
A0A6A9JQQ8_PSEAI
358
0
38350
TrEMBL
-
A0A8G4C9W3_PSEAI
357
0
38940
TrEMBL
-
A0A3N0FB14_PSEAI
363
0
38754
TrEMBL
-
A0A8G7H8S3_PSEAI
357
0
39000
TrEMBL
-
A0A8G5T4G8_PSEAI
357
0
38970
TrEMBL
-
A0A8G3JJB4_PSEAI
357
0
39012
TrEMBL
-
A0A8B4ZNV7_PSEAI
357
0
38998
TrEMBL
-
A0A8G3JLS2_PSEAI
358
0
38397
TrEMBL
-
A0A8G7NGV3_PSEAI
357
0
38976
TrEMBL
-
A0A8F9NXS2_PSEAI
358
0
38340
TrEMBL
-
A0A8F9V9U8_PSEAI
363
0
38701
TrEMBL
-
A0A8G4HTK4_PSEAI
358
0
38479
TrEMBL
-
A0A8G1Q5T9_PSEAI
363
0
38728
TrEMBL
-
A0A8G7TFU1_PSEAI
363
0
38756
TrEMBL
-
A0A2R7XJF2_PSEAI
357
0
38984
TrEMBL
-
A0A7M3B5H3_PSEAI
357
0
39030
TrEMBL
-
A0A8F9VFY1_PSEAI
357
0
39056
TrEMBL
-
A0A8G6ZVL3_PSEAI
357
0
39014
TrEMBL
-
A0A6A9JZX0_PSEAI
357
0
39053
TrEMBL
-
A0A3S0J1M5_PSEAI
358
0
38513
TrEMBL
-
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
38337
-
2 * 38337, calculated from amino acid sequence
39068
-
2 * 39068, calculated from amino acid sequence
40000
-
2 * 40000, SDS-PAGE
80000
-
gel filtration
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
dimer
each monomer is comprised of two domains, an eight-stranded alpha/beta barrel containing the pyridoxal 5'-phosphate cofactor and a second domain primarily composed of beta-strands
homodimer
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
sitting drops equilibrated versus 1.5 M (NH4)2SO4, 2% polyethylene glycol 400 and 0.1 M HEPES, pH 7.5, crystal strcuture at 1.45 A resolution
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant enzymes Alr and DadX
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
cloning of two independent alanine racemases in Escherichia coli: Alr and DadX
-
expressed in Escherichia coli BL21(DE3) cells
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
drug development
Alr is a target for the development of antibacterial drugs
medicine
-
the requirement for D-Ala as a necessary component of the bacterial cell wall makes the enzyme a logical target for the development of novel antibiotics
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Lacoste, A.M.; Darriet, M.; Neuzil, E.; Le Goffic, F.
Inhibition of alanine racemase by vinylglycine and its phosphonic analogue: a 1H nuclear magnetic resonance spectroscopy study
Biochem. Soc. Trans.
16
606-608
1988
Pseudomonas aeruginosa, Pseudomonas aeruginosa A237
-
Manually annotated by BRENDA team
LeMagueres, P.; Im, H.; Dvorak, A.; Strych, U.; Benedik, M.; Krause, K.L.
Crystal structure at 1.45 A resolution of alanine racemase from a pathogenic bacterium, Pseudomonas aeruginosa, contains both internal and external aldimine forms
Biochemistry
42
14752-14761
2003
Pseudomonas aeruginosa (Q9HTQ2), Pseudomonas aeruginosa
Manually annotated by BRENDA team
Strych, U.; Huang, H.C.; Krause, K.L.; Benedik, M.J.
Characterization of the alanine racemases from Pseudomonas aeruginosa PAO1
Curr. Microbiol.
41
290-294
2000
Pseudomonas aeruginosa
Manually annotated by BRENDA team
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)
Manually annotated by BRENDA team
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
Manually annotated by BRENDA team
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)
Manually annotated by BRENDA team