5.1.1.1: alanine racemase
This is an abbreviated version!
For detailed information about alanine racemase, go to the full flat file.
Word Map on EC 5.1.1.1
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5.1.1.1
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pyridoxal
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5'-phosphate
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peptidoglycan
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racemization
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d-cycloserine
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stearothermophilus
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plp-dependent
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d-amino
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aldimine
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d-alanyl-d-alanine
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exosporium
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pyridoxal-5'-phosphate-dependent
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drug development
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5'-phosphate-dependent
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d-alanine:d-alanine
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medicine
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biotechnology
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pharmacology
- 5.1.1.1
- pyridoxal
- 5'-phosphate
- peptidoglycan
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racemization
- d-cycloserine
- stearothermophilus
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plp-dependent
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d-amino
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aldimine
- d-alanyl-d-alanine
- exosporium
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pyridoxal-5'-phosphate-dependent
- drug development
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5'-phosphate-dependent
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d-alanine:d-alanine
- medicine
- biotechnology
- pharmacology
Reaction
Synonyms
1SFT, AAR, alanine racemase, AlaR, ALR, alr-2, ALR1, ALR2, Alr2 racemase, AlrA, AlrAba, AlrBax, AlrMtb, alrTt, ARL, BA0252, BAS0238, CBL/ALR, CdAlr, cystathionine beta-lyase, D-alanine racemase, DadB, DadX, dadXOF4, dal1, EcAlr, EcCBL, EfAlaR, L-Alanine racemase, L-Alanine:D-alanine racemase, MBalr1, MBAlr2, MetC, More, MurI, OEOE_1641, PDB, Racemase, alanine, tAlaRac, TmCBL, wMelCBL
ECTree
5.1.1.1 alanine racemaseAdvanced search results
results (
results (Inhibitors
Inhibitors on EC 5.1.1.1 - alanine racemase
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INHIBITOR 
ORGANISM
UNIPROT
COMMENTARY 
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
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(6R)-3-[(D-alanyloxy)methyl]-8-oxo-7-[2-(thiophen-2-yl)acetamido]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
1,1'-(2-oxido-1,2,5-oxadiazole-3,4-diyl)-bis (1-(2-thienyl))-methanone
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2-(4,6-dimethyl-3-oxo-[1,2]thiazolo[5,4-b]pyridin-2-yl)-N-[2-(4-ethoxyphenyl)ethyl]acetamide
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2-N',2-N',7-N',7-N'-tetramethyl-9H-fluorene-2,7-disulfonohydrazide
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4-[4-(propan-2-yl)phenyl]-2-[4-[(trifluoromethyl)sulfanyl]phenyl]-1,2,4-thiadiazolidine-3,5-dione
5-chloro-N-(3-chloro-4-methoxyphenyl)-2-(methylsulfonyl)pyrimidine-4-carboxamide
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6-O-[3-chloro-4-(6-methoxycarbonylpyridine-2-carbonyl)oxyphenyl] 2-O-methyl pyridine-2,6-dicarboxylate
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DTT
DTT at 1 mmol/l inhibits 67% of the enzyme activity compared with the control and DTT at 5 mmol/l results in complete inhibition of the enzyme activity
FAD
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slight activation at low concentrations, inhibition at high concentrations
homogentisic acid
competitive inhibition, has minimal cytotoxicity against mammalian cells. Homogentisic acid binds to the active site of the racemase
hydroquinone
noncompetitive inhibition, has minimal cytotoxicity against mammalian cells. Hydroquinone binds near the active center of alanine racemase
O-Carbamoyl-D-Ser
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inhibition of wild type enzyme but not of the O-carbamoyl-D-Ser mutant
[4-(5-butyl-5-methyl-2(5H)-furanylidene)dihydro-3,5-dioxo-2(3H)-furanylidene]acetic acid
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(2S)-1-oxo-1-([(1R)-1-phosphonoethyl]amino)propan-2-yl L-methioninate
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(2S)-1-oxo-1-([(1R)-1-phosphonoethyl]amino)propan-2-yl L-methioninate
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(2S)-1-oxo-1-([(1R)-1-phosphonoethyl]amino)propan-2-yl L-methioninate
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(2S)-1-oxo-1-([(1R)-1-phosphonoethyl]amino)propan-2-yl L-methioninate
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(2S)-1-oxo-1-[[(1R)-1-phosphonoethyl]amino]propan-2-yl L-methioninate
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(2S)-1-oxo-1-[[(1R)-1-phosphonoethyl]amino]propan-2-yl L-methioninate
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(6R)-3-[(D-alanyloxy)methyl]-8-oxo-7-[2-(thiophen-2-yl)acetamido]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
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(6R)-3-[(D-alanyloxy)methyl]-8-oxo-7-[2-(thiophen-2-yl)acetamido]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
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(6R)-3-[(D-alanyloxy)methyl]-8-oxo-7-[2-(thiophen-2-yl)acetamido]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
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(6R)-3-[(D-alanyloxy)methyl]-8-oxo-7-[2-(thiophen-2-yl)acetamido]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
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(R)-1-aminoethylphosphonic acid
Q81VF6
in combination with pyridoxal 5'-phosphate
(R)-1-aminoethylphosphonic acid
upon formation of the external aldimine the phosphonate group interacts with putative catalytic residues, thereby rendering them unavailable for catalysis
2-(2-chloro-4-nitrophenyl)-4-(2,3-dihydro-1H-inden-2-yl)-1,2,4-thiadiazolidine-3,5-dione
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2-(2-chloro-4-nitrophenyl)-4-(2,3-dihydro-1H-inden-2-yl)-1,2,4-thiadiazolidine-3,5-dione
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2-(2-chloro-4-nitrophenyl)-4-(cyclopropylmethyl)-1,2,4-thiadiazolidine-3,5-dione
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2-(2-chloro-4-nitrophenyl)-4-(cyclopropylmethyl)-1,2,4-thiadiazolidine-3,5-dione
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2-(2-chloro-6-methylphenyl)-4-(cyclopropylmethyl)-1,2,4-thiadiazolidine-3,5-dione
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2-(2-chloro-6-methylphenyl)-4-(cyclopropylmethyl)-1,2,4-thiadiazolidine-3,5-dione
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2-(3,5-dimethyl-1,2-oxazol-4-yl)-4-(4-fluorophenyl)-1,2,4-thiadiazolidine-3,5-dione
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2-(3,5-dimethyl-1,2-oxazol-4-yl)-4-(4-fluorophenyl)-1,2,4-thiadiazolidine-3,5-dione
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2-(3-chloro-4-fluorophenyl)-4-(2,3-dihydro-1H-inden-2-yl)-1,2,4-thiadiazolidine-3,5-dione
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2-(3-chloro-4-fluorophenyl)-4-(2,3-dihydro-1H-inden-2-yl)-1,2,4-thiadiazolidine-3,5-dione
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4-(2,3-dihydro-1H-inden-2-yl)-2-[(3-ethylphenyl)methyl]-1,2,4-thiadiazolidine-3,5-dione
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4-(2,3-dihydro-1H-inden-2-yl)-2-[(3-ethylphenyl)methyl]-1,2,4-thiadiazolidine-3,5-dione
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4-(cyclopropylmethyl)-2-(3,5-dimethyl-1,2-oxazol-4-yl)-1,2,4-thiadiazolidine-3,5-dione
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4-(cyclopropylmethyl)-2-(3,5-dimethyl-1,2-oxazol-4-yl)-1,2,4-thiadiazolidine-3,5-dione
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4-(cyclopropylmethyl)-2-[2-(trifluoromethyl)phenyl]-1,2,4-thiadiazolidine-3,5-dione
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4-(cyclopropylmethyl)-2-[2-(trifluoromethyl)phenyl]-1,2,4-thiadiazolidine-3,5-dione
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4-[4-(propan-2-yl)phenyl]-2-[4-[(trifluoromethyl)sulfanyl]phenyl]-1,2,4-thiadiazolidine-3,5-dione
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4-[4-(propan-2-yl)phenyl]-2-[4-[(trifluoromethyl)sulfanyl]phenyl]-1,2,4-thiadiazolidine-3,5-dione
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acetate
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enzyme-inhibitor complex structure, with pyridoxyl 5'-phosphate, PDB ID 1SFT
alafosfalin
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effective in reducing D-alanine pool levels, alafosfalin forms an external aldimine with the bound PLP cofactor, but is neither racemised nor efficiently hydrolyzed and upon formation of the external aldimine, the phosphonate group interacts with putative catalytic residues and thereby renders them unavailable for catalysis
alafosfalin
selective inhibitor of peptidoglycan biosynthesis in both Grampositive and Gram-negative bacteria
alafosfalin
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effective in reducing D-alanine pool levels, alafosfalin forms an external aldimine with the bound PLP cofactor, but is neither racemised nor efficiently hydrolyzed and upon formation of the external aldimine, the phosphonate group interacted with putative catalytic residues and thereby renders them unavailable for catalysis
beta,beta,beta-trifluoroalanine
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nucleophilic attack of Lys38 on the electrophilic beta-difluoro-alpha,beta-unsaturated imine
beta,beta,beta-trifluoroalanine
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nucleophilic attack of Lys38 on the electrophilic beta-difluoro-alpha,beta-unsaturated imine
beta-Chloro-D-alanine
BCDA, its primary target is glutamate racemase, poor activity oagainst alanine racemase activity, potent antituberculosis activity. BCDA does not inhibit the D-alanine pathway in intact cells, consistent with its poor in vitro activity, it is instead an irreversible mechanism-based inactivator of glutamate racemase (MurI), an upstream enzyme in the same early stage of peptidoglycan biosynthesis. Inhibition kinetics, overview. Glutamate racemase (MurI) is a pyridoxal 5'-phosphate-independent racemase and is therefore unable to undergo the same mechanism of inhibition as Alr with BCDA
beta-Chloro-D-alanine
BCDA, the compund is a very poor inhibitor of recombinant Mycobacterium tuberculosis Alr, despite having potent antituberculosis activity, its primary target is glutamate racemase, poor activity oagainst alanine racemase activity, potent antituberculosis activity. BCDA does not inhibit the D-alanine pathway in intact cells, consistent with its poor in vitro activity, it is instead an irreversible mechanism-based inactivator of glutamate racemase (MurI), an upstream enzyme in the same early stage of peptidoglycan biosynthesis. Inhibition kinetics, overview. Glutamate racemase (MurI) is a pyridoxal 5'-phosphate-independent racemase and is therefore unable to undergo the same mechanism of inhibition as Alr with BCDA
beta-Chloro-D-alanine
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effective in the inhibition of bacterial growth
beta-chloro-L-alanine
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effective in the inhibition of bacterial growth like that of the D-isomer. But the L-isomer has less specificity towards the concerned Alr enzymes due to its inhibitory activity towards decarboxylase and transaminases. This results in the blockage of the production of essential L-amino acids with a loss of viability of bacterial and mammalial cells
beta-chloroalanine
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enantiomers of beta-chloroalanine as Alr inhibitors
cycloserine
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8 microg/ml bacterial culture extract markedly inhibits alanine racemase
cycloserine
D-cycloserine or a racemic mixture of D- and L-cycloserine
D-cycloserine
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importance of N2-structural site in cyloserine for bioactivity
D-cycloserine
active site bound inhibitor, binding structure, overview
D-cycloserine
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importance of N2-structural site in cyloserine for bioactivity
D-cycloserine
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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
D-cycloserine
model for inactivation mechanism via geminal diamine and ketimine to isoxazole
D-cycloserine
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mechanism of inactivation and comparison with inactivation of Streptomyces lavendulae enzyme
D-cycloserine
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importance of N2-structural site in cyloserine for bioactivity
D-cycloserine
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importance of N2-structural site in cyloserine for bioactivity
D-cycloserine
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importance of N2-structural site in cyloserine for bioactivity
D-cycloserine
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importance of N2-structural site in cyloserine for bioactivity
D-cycloserine
specific inhibition is reversible by D-alanine in the growth medium
D-cycloserine
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DCS, inhibits enzyme Alr irreversibly by covalently bonding to pyridoxal 5'-phosphate, molecular modeling
D-cycloserine
competitive inhibition, importance of N2-structural site in cyloserine for bioactivity
D-cycloserine
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competitive inhibitor, importance of N2-structural site in cyloserine for bioactivity
D-cycloserine
structural features such as the hinge angle or the surface area between the monomers do not contribute to D-cycloserine resistance, binding structure analysis, overview
D-cycloserine
time-dependent inactivation rate of enzyme from Streptomyces lavendulae is slower than for enzyme from Escherichia coli. Enzyme from Streptomyces lavendulae is one of its self-resistance determinants
D-cycloserine
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mechanism of inactivation and comparison with inactivation of Bacillus stearothermophilus enzyme
hydroxylamine
via elimanting the cofactor pyridoxal-5'-phosphate from the enzyme
L-Cycloserine
competitive inhibition, importance of N2-structural site in cyloserine for bioactivity
L-Cycloserine
model for inactivation mechanism via geminal diamine and ketimine to isoxazole
L-Cycloserine
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mechanism of inactivation and comparison with inactivation of Streptomyces lavendulae enzyme
L-Cycloserine
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importance of N2-structural site in cyloserine for bioactivity
L-Cycloserine
competitive inhibition, importance of N2-structural site in cyloserine for bioactivity
L-Cycloserine
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competitive inhibitor, importance of N2-structural site in cyloserine for bioactivity
L-Cycloserine
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mechanism of inactivation and comparison with inactivation of Bacillus stearothermophilus enzyme
L-leucyl-N-[(1R)-1-phosphonoethyl]-L-alaninamide
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N2-(2-aminodecanoyl)-N-[(1R)-1-phosphonoethyl]-L-alaninamide
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norleucyl-N-[(1R)-1-phosphonoethyl]-L-alaninamide
moderate in vivo activity
norvalyl-N-[(1R)-1-phosphonoethyl]-L-alaninamide
moderate in vivo activity
O-carbamoyl-D-serine
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good inhibitor, determination of primary site of action is based on the observed accumulation of UDP-MurNAc-L-Ala-D-Glu-L-Lys and on the absence of D-Ala-O-carbamyl-D-serine accumulation
propionate
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propionate influences both Km (affinity for substrate) and Vmax (enzyme catalysis)
pyridoxal 5'-phosphate
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slight activation at low concentrations, inhibition at high concentrations
Sodium borohydride
complete inactivation after dialysis against
Sodium borohydride
reduction of the enzyme by dialysis with sodium borohydride, the reduced enzyme is catalytically inactive and addition of pyridoxal 5'-phosphate does not reverse the inactivation
Sodium borohydride
reduction of the enzyme by dialysis with sodium borohydride, the reduced enzyme is catalytically inactive and addition of pyridoxal 5'-phosphate does not reverse the inactivation
Sodium borohydride
reduction of the enzyme by dialysis with sodium borohydride, the reduced enzyme is catalytically inactive and addition of pyridoxal 5'-phosphate does not reverse the inactivation
Sodium borohydride
reduction of the enzyme by dialysis with sodium borohydride, the reduced enzyme is catalytically inactive and addition of pyridoxal 5'-phosphate does not reverse the inactivation
additional information
inhibitor screening of a library of 2100 compounds, and molecular docking study
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additional information
the enzyme activity is not sensitive to the metal chelating agent EDTA indicating that divalent cations are not required for enzyme activity
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additional information
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no inhibition by O-carbamoyl-L-serine
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additional information
wild-type enzyme ALR is strongly activated by low concentrations (e.g. 1 mM) of short-chain carboxylates, and is inhibited at higher concentrations (e.g. 10 mM). The enzyme mutant ALRA131K is inhibited at all carboxylate concentrations tested (1-40 mM). Both propionate and butyrate strongly inhibit mutant ALRA131K. ALR and ALRA131K are both inhibited by DL-lactate, though wild-type ALR is inhibited to a lesser degree than ALRA131K. In addition, succinate, pyruvate, 2-oxoglutarate, oxaloacetate, and aspartate also more strongly inhibit mutant ALRA131K than wild-type ALR
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additional information
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wild-type enzyme ALR is strongly activated by low concentrations (e.g. 1 mM) of short-chain carboxylates, and is inhibited at higher concentrations (e.g. 10 mM). The enzyme mutant ALRA131K is inhibited at all carboxylate concentrations tested (1-40 mM). Both propionate and butyrate strongly inhibit mutant ALRA131K. ALR and ALRA131K are both inhibited by DL-lactate, though wild-type ALR is inhibited to a lesser degree than ALRA131K. In addition, succinate, pyruvate, 2-oxoglutarate, oxaloacetate, and aspartate also more strongly inhibit mutant ALRA131K than wild-type ALR
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additional information
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N2-substitution of carboxybenzyl-protected derivatives of D,L-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 N2 position exhibits modest inhibitory activity against purified Alr enzyme from Mycobacterium tuberculosis, Ki = 0.36 mM
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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
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additional information
the active-site binding pocket, dimer interface and active-site entryway of the enzyme are potential targets for structure-aided inhibitor design, formation of a template for structure-based drug-development efforts targeting the enzyme, overview
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additional information
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the active-site binding pocket, dimer interface and active-site entryway of the enzyme are potential targets for structure-aided inhibitor design, formation of a template for structure-based drug-development efforts targeting the enzyme, overview
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additional information
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no inhibition by O-carbamoyl-L-serine. N2-substitution of carboxybenzyl-protected derivatives of D,L-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 Streptococcus aureus, Ki = 1.16 mM
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