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Information on EC 5.1.1.1 - alanine racemase
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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
-
racemization
- peptidoglycan
- stearothermophilus
- d-cycloserine
-
plp-dependent
-
d-amino
-
aldimine
- d-alanyl-d-alanine
- exosporium
- drug development
-
pyridoxal-5'-phosphate-dependent
-
d-alanine:d-alanine
-
5'-phosphate-dependent
- pharmacology
- medicine
- biotechnology
The enzyme appears in viruses and cellular organisms
Synonyms
alanine racemase, alr-2, d-alanine racemase, alrbax, mbalr2, alrtt, l-alanine racemase, alraba, cdalr, alr2 racemase, 
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
alanine racemase
AlaR
ALR
alr-2
ALR2
Alr2 racemase
CdAlr
DadB
DadX
dadXOF4
MurI
OEOE_1641
ALR
Pseudomonas aeruginosa ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C / PRS 101 / PAO1
-
alr-2
Aeromonas hydrophila subsp. hydrophila HBNUAh01 / ATCC 7966 / DSM 30187 / JCM 1027 / KCTC 2358 / NCIMB 9240
-
alr-2
Aeromonas hydrophila subsp. hydrophila HBNUAh01 / ATCC 7966 / DSM 30187 / JCM 1027 / KCTC 2358 / NCIMB 9240
gen ename
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
L-alanine = D-alanine
-
-
-
-
L-alanine = D-alanine
the alanine racemase builds two different bases in the active site. The base for D-Ala may be closer to the enzyme surface, and that for L-Ala inside
-
L-alanine = D-alanine
the active site of the alanine racemase reacts asymmetrically with the enantiomers of the substrate and has a conformation which greatly favors the D-enantiomer
-
L-alanine = D-alanine
consensus water sites at the interface between the two enzyme monomers maintain and stabilize dimer and supply the active site continuously with water molecules to allow rapid equilibration of active site protons
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
racemization
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PATHWAY SOURCE
PATHWAYS
BRENDA
KEGG
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SYSTEMATIC NAME
IUBMB Comments
alanine racemase
A pyridoxal-phosphate protein.
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CAS REGISTRY NUMBER
COMMENTARY
9024-06-0
-
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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
D-lysine
L-lysine
enzyme mutant I222T/Y354W, no activity with the wild-type enzyme
-
?
L-2-Aminobutyrate
D-2-Aminobutyrate
0.37% of the activity with L-Ala
-
r
L-2-aminobutyric acid
D-2-aminobutyric acid
-
18% of the activity with L-Ala
-
?
L-Arg
D-Arg
-
stepwise mechanism for alanine racemase at both 25°C and at 65°C. The carbanionic intermediate is obligatory, and Arg219 may serve to destabilize it to avoid side reactions such as transamination, a detailed reaction mechanism is proposed that includes enzyme and substrate protonation states
-
r
L-arginine
D-arginine
less than 10% activity compared to L-alanine
-
r
L-Methionine
D-Methionine
less than 10% activity compared to L-alanine
-
r
L-phenylalanine
D-phenylalanine
1.1% activity compared to L-alanine
-
r
L-proline
D-proline
1.1% activity compared to L-alanine
-
r
L-valine
D-valine
less than 10% activity compared to L-alanine
-
r
L-Ala
?
-
enzyme provides D-Ala as an essential building block for biosynthesis of the peptidoglycan layer of the cell wall
-
?
L-Ala
?
-
enzyme provides D-Ala as an essential building block for biosynthesis of the peptidoglycan layer of the cell wall
-
?
L-Ala
?
-
enzyme provides D-Ala as an essential building block for biosynthesis of the peptidoglycan layer of the cell wall
-
?
L-Ala
?
-
enzyme provides D-Ala as an essential building block for biosynthesis of the peptidoglycan layer of the cell wall
-
?
L-Ala
D-Ala
-
the enzyme catalyzes transamination as a side function.The pyridoxal form of the enzyme is converted to the pyridoxamine form by incubation with its natural substrate, D-alanine or L-alanine, under acidic conditions: the enzyme loses its racemase activity concomitantly. The pyridoxamine form of the enzyme returns to the pyridoxal form by incubation with pyruvate at alkaline pH
-
r
L-Ala
D-Ala
-
Tyr265 and Lys39 are the catalytic bases removing alpha-hydrogen from L- and D-alanine
-
r
L-Ala
D-Ala
the enzyme catalyzes the first committed step in bacterial cell wall biosynthesis
-
?
L-Ala
D-Ala
-
the ratio of the activity for conversion of D-alanine to L-alanine to that of the reverse conversion is constantly about 0.5 in the pH range 7-9.5
-
r
L-Ala
D-Ala
-
enzyme is required for production of D-Ala, a necessary component of the bacterial cell wall
-
?
L-alanine
D-alanine
Aeromonas hydrophila subsp. hydrophila HBNUAh01 / ATCC 7966 / DSM 30187 / JCM 1027 / KCTC 2358 / NCIMB 9240
-
-
r
L-alanine
D-alanine
Q81VF6
-
enzyme provides D-Ala as a required compound for the synthesis of the peptidoglycan layer of the bacterial cell wall, Tolypocladium niveum requires alanine racemase for cyclosporin biosynthesis
r
L-alanine
D-alanine
-
alanine racemase can discriminate effectively between L-alanine and L-2-aminobutyric acid, and selectively and reversibly catalyzes L-alanine to D-alanine transformation Therefore, the enzyme shows ability of eliminating L-Ala from the reaction mixtures of L-2-aminobutyric acid biosynthesis, method optimization and evaluation in a coupled reaction with D-amino acid oxidase converting D-alanine to pyruvate stereoselectively, overview
-
r
L-alanine
D-alanine
-
-
responsible for the synthesis of the d-alanine moiety present in cyclosporin A and of HC-toxin
?
L-alanine
D-alanine
TOXG encodes an alanine racemase whose function is to synthesize D-Ala for incorporation into HC-toxin, enzyme is involved in cyclic peptide biosynthesis
-
?
L-alanine
D-alanine
catalyzes the interconversion of D-alanine and L-alanine
-
r
L-alanine
D-alanine
catalyzes the interconversion of D-alanine and L-alanine, highly preferred substrate
-
r
L-alanine
D-alanine
reversible racemization
-
r
L-alanine
D-alanine
first step in the biosynthesis of the peptidoglycan
-
?
L-alanine
D-alanine
-
The bacterium utilizes D-alanine (DAla) for synthesis of the peptidoglycan cell wall.
-
r
L-alanine
D-alanine
-
a major component of the alanine pathway, D-alanine is a major component in cell wall synthesis
-
?
L-alanine
D-alanine
catalyzes the interconversion of D-alanine and L-alanine
-
r
L-alanine
D-alanine
catalyzes the interconversion of D-alanine and L-alanine
-
r
L-alanine
D-alanine
Pseudomonas aeruginosa ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C / PRS 101 / PAO1
-
-
r
L-alanine
D-alanine
-
responsible for the synthesis of the d-alanine moiety present in cyclosporin A and of HC-toxin
-
?
L-alanine
D-alanine
-
reversible reaction from an external aldimine in both directions via a quinonoid intermediate, overview
-
r
L-leucine
D-leucine
-
activity is 20% compared with L-alanine, other amino acids are not racemized
-
r
L-leucine
D-leucine
0.9% activity compared to L-alanine
-
r
L-lysine
D-lysine
less than 10% activity compared to L-alanine
-
r
L-lysine
D-lysine
enzyme mutant I222T/Y354W, no activity with the wild-type enzyme
-
?
L-serine
D-serine
less than 10% activity compared to L-alanine
-
r
additional information
?
-
assay method optimization and validation, overview
-
?
additional information
?
-
Aeromonas hydrophila subsp. hydrophila HBNUAh01 / ATCC 7966 / DSM 30187 / JCM 1027 / KCTC 2358 / NCIMB 9240
assay method optimization and validation, overview
-
?
additional information
?
-
-
exchange of the alpha-hydrogen of D-Ala and L-Ala with D2O
-
?
additional information
?
-
high specificity to L-alanine, low activity with L-arginine, L-methionine, L-lysine, L-serine, L-valine, L-proline, L-phenylalanine, L-leucine, respectively, no activity with L-histidine
-
?
additional information
?
-
the enzyme is absolutely specific for L-alanine compared to other L-amino acids, overview
-
?
additional information
?
-
-
purified chlamydial GlyA also exhibits racemase activity on L-Ala in vitro
-
?
additional information
?
-
Alr2 can interconvert L- and D-serine and Alr2 binds to L- and D-serine with 2fold weaker affinity to that of L- and D-alanine, cf. EC 5.1.1.18
-
?
additional information
?
-
-
Alr2 can interconvert L- and D-serine and Alr2 binds to L- and D-serine with 2fold weaker affinity to that of L- and D-alanine, cf. EC 5.1.1.18
-
?
additional information
?
-
Alr2 converts L-serine to an approximately equal amount of D-serine. When tested with D-serine, Alr2 does not convert as much, and nearly 75% of the D-serine remains in the D-form
-
?
additional information
?
-
-
Alr2 converts L-serine to an approximately equal amount of D-serine. When tested with D-serine, Alr2 does not convert as much, and nearly 75% of the D-serine remains in the D-form
-
?
additional information
?
-
Alr2 can interconvert L- and D-serine and Alr2 binds to L- and D-serine with 2fold weaker affinity to that of L- and D-alanine, cf. EC 5.1.1.18
-
?
additional information
?
-
Alr2 converts L-serine to an approximately equal amount of D-serine. When tested with D-serine, Alr2 does not convert as much, and nearly 75% of the D-serine remains in the D-form
-
?
additional information
?
-
-
the enzyme catalyzes transamination as side reaction, R-isomer preference in the hydrogen abstraction from pyridoxamine 5'-phosphate
-
?
additional information
?
-
-
the epsilon-amino group of Lys39 participates in both racemization and transamination when catalyzed by the wild-type enzyme
-
?
additional information
?
-
residues Ile222 and Tyr354 are important for the enzyme substrate specificity
-
?
additional information
?
-
-
residues Ile222 and Tyr354 are important for the enzyme substrate specificity
-
?
additional information
?
-
-
no racemization of L-Ser, L-Asp, L-Glu, L-Val and L-Arg
-
?
additional information
?
-
-
the enzyme is only specific to L-alanine and L-isoleucine, and does not catalyze isomerization the other amino acids
-
?
additional information
?
-
-
the enzyme is only specific to L-alanine and L-isoleucine, and does not catalyze isomerization the other amino acids
-
?
additional information
?
-
-
alr racemase is constitutive and serves an anabolic function, dadB encoded enzyme is inducible and required for cell growth on L-Ala
-
?
additional information
?
-
-
alr racemase is constitutive and serves an anabolic function, dadB encoded enzyme is inducible and required for cell growth on L-Ala
-
?
additional information
?
-
-
two nonhomologous alanine racemase genes, one of which is associated with the catabolic function and the other of which presumably represents the biosynthetic function
-
?
additional information
?
-
-
key enzyme in cyclosporin A biosynthesis
-
?
additional information
?
-
-
Tolypocladium inflatum alanine racemase is able to catalyse retroaldol cleavage and transamination reactions, kinetic analysis and reaction mechanisms, overview
-
?
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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
L-Ala
?
-
enzyme provides D-Ala as an essential building block for biosynthesis of the peptidoglycan layer of the cell wall
-
-
?
L-Ala
?
-
enzyme provides D-Ala as an essential building block for biosynthesis of the peptidoglycan layer of the cell wall
-
-
?
L-Ala
?
-
enzyme provides D-Ala as an essential building block for biosynthesis of the peptidoglycan layer of the cell wall
-
-
?
L-Ala
?
-
enzyme provides D-Ala as an essential building block for biosynthesis of the peptidoglycan layer of the cell wall
-
-
?
L-Ala
D-Ala
the enzyme catalyzes the first committed step in bacterial cell wall biosynthesis
-
?
L-Ala
D-Ala
-
enzyme is required for production of D-Ala, a necessary component of the bacterial cell wall
-
?
L-alanine
D-alanine
Aeromonas hydrophila subsp. hydrophila HBNUAh01 / ATCC 7966 / DSM 30187 / JCM 1027 / KCTC 2358 / NCIMB 9240
-
-
-
r
L-alanine
D-alanine
Q81VF6
-
enzyme provides D-Ala as a required compound for the synthesis of the peptidoglycan layer of the bacterial cell wall, Tolypocladium niveum requires alanine racemase for cyclosporin biosynthesis
-
r
L-alanine
D-alanine
-
-
responsible for the synthesis of the d-alanine moiety present in cyclosporin A and of HC-toxin
-
?
L-alanine
D-alanine
TOXG encodes an alanine racemase whose function is to synthesize D-Ala for incorporation into HC-toxin, enzyme is involved in cyclic peptide biosynthesis
-
?
L-alanine
D-alanine
catalyzes the interconversion of D-alanine and L-alanine
-
-
r
L-alanine
D-alanine
first step in the biosynthesis of the peptidoglycan
-
-
?
L-alanine
D-alanine
-
The bacterium utilizes D-alanine (DAla) for synthesis of the peptidoglycan cell wall.
-
-
r
L-alanine
D-alanine
-
a major component of the alanine pathway, D-alanine is a major component in cell wall synthesis
-
-
?
L-alanine
D-alanine
catalyzes the interconversion of D-alanine and L-alanine
-
-
r
L-alanine
D-alanine
catalyzes the interconversion of D-alanine and L-alanine
-
-
r
L-alanine
D-alanine
Pseudomonas aeruginosa ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C / PRS 101 / PAO1
-
-
-
r
L-alanine
D-alanine
-
responsible for the synthesis of the d-alanine moiety present in cyclosporin A and of HC-toxin
-
-
?
additional information
?
-
Alr2 can interconvert L- and D-serine and Alr2 binds to L- and D-serine with 2fold weaker affinity to that of L- and D-alanine, cf. EC 5.1.1.18
-
-
?
additional information
?
-
-
Alr2 can interconvert L- and D-serine and Alr2 binds to L- and D-serine with 2fold weaker affinity to that of L- and D-alanine, cf. EC 5.1.1.18
-
-
?
additional information
?
-
Alr2 can interconvert L- and D-serine and Alr2 binds to L- and D-serine with 2fold weaker affinity to that of L- and D-alanine, cf. EC 5.1.1.18
-
-
?
additional information
?
-
-
alr racemase is constitutive and serves an anabolic function, dadB encoded enzyme is inducible and required for cell growth on L-Ala
-
-
?
additional information
?
-
-
alr racemase is constitutive and serves an anabolic function, dadB encoded enzyme is inducible and required for cell growth on L-Ala
-
-
?
additional information
?
-
-
two nonhomologous alanine racemase genes, one of which is associated with the catabolic function and the other of which presumably represents the biosynthetic function
-
-
?
additional information
?
-
-
key enzyme in cyclosporin A biosynthesis
-
-
?
additional information
?
-
-
Tolypocladium inflatum alanine racemase is able to catalyse retroaldol cleavage and transamination reactions, kinetic analysis and reaction mechanisms, overview
-
-
?
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
FAD
-
not required as cofactor, slight activation at low concentrations, inhibition at high concentrations
pyridoxal 5'-phosphate
-
the monomeric inactive enzyme appears to bind the cofactor pyridoxal 5'-phosphate by a non-covalent linkage, although the native dimeric enzyme binds the cofactor through an aldimine Schiff base linkage
pyridoxal 5'-phosphate
-
not required as cofactor, slight activation at low concentrations, inhibition at high concentrations
pyridoxal 5'-phosphate
-
pyridoxal 5'-phosphate binds to Lys of the enzyme protein and forms an aldimine Schiff base. The alpha-proton of the substrate is then abstracted, and the pyridoxal 5'-phosphate carbanion is generated
pyridoxal 5'-phosphate
-
pyridoxal 5'-phosphate binds to Lys of the enzyme protein and forms an aldimine Schiff base. The alpha-proton of the substrate is then abstracted, and the pyridoxal 5'-phosphate carbanion is generated
pyridoxal 5'-phosphate
-
pyridoxal 5'-phosphate binds to Lys of the enzyme protein and forms an aldimine Schiff base. The alpha-proton of the substrate is then abstracted, and the pyridoxal 5'-phosphate carbanion is generated
pyridoxal 5'-phosphate
-
pyridoxal 5'-phosphate binds to Lys of the enzyme protein and forms an aldimine Schiff base. The alpha-proton of the substrate is then abstracted, and the pyridoxal 5'-phosphate carbanion is generated
pyridoxal 5'-phosphate
-
the sequence of 10 amino acid residues around the Lys residue, to which pyridoxal 5'-phosphate is bound, is identical with that of the dadB racemase
pyridoxal 5'-phosphate
-
1 mol of pyridoxal 5'-phosphate is bound per subunit
pyridoxal 5'-phosphate
-
pyridoxal 5'-phosphate dependent enzyme
pyridoxal 5'-phosphate
-
pyridoxal 5'-phosphate dependent enzyme
pyridoxal 5'-phosphate
-
2 mol of pyridoxal 5'-phosphate bound per mol of enzyme dimer
pyridoxal 5'-phosphate
-
2 mol of pyridoxal 5'-phosphate bound per mol of enzyme dimer
pyridoxal 5'-phosphate
-
Arg219 forms a hydrogen bond with the pyridine nitrogen of the cofactor, Arg136 donates a hydrogen bond to the phenolic oxygen of pyridoxal 5'-phosphate and may be involved in the binding of substrate as well as stabilization of intermediates
pyridoxal 5'-phosphate
-
Km: 0.000033 mM
pyridoxal 5'-phosphate
-
contains one mol of pyridoxal 5'-phosphate per mol of enzyme
pyridoxal 5'-phosphate
dependent on
pyridoxal 5'-phosphate
both active sites of the dimer contain a pyridoxal 5'-phosphate molecule in aldimine linkage to Lys39 as a protonated Schiff base. The protonated pyridoxal 5'-phosphate-Lys39 Schiff base is the reactive form of the enzyme
pyridoxal 5'-phosphate
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. The cofactor adopts two partially occupied conformational states that resemble previously reported and external aldimine complexes
pyridoxal 5'-phosphate
-
enzyme is dependent on, maximal activity at 0.025 mM
pyridoxal 5'-phosphate
-
Km at 30°C is 0.005 mM. Maximal activity is obtained in presence of more than 0.125 mM pyridoxal 5'-phosphate. The decrease in activity at incubation temperatures over 40°C is consistent with the decrease in the amount of bound pyridoxal 5'-phosphate
pyridoxal 5'-phosphate
-
the pyridoxal form of the enzyme is converted to the pyridoxamine form by incubation with its natural substrate, D-alanine or L-alanine, under acidic conditions: the enzyme loses its racemase activity concomitantly. The pyridoxamine form of the enzyme returns to the pyridoxal form by incubation with pyruvate at alkaline pH
pyridoxal 5'-phosphate
Q81VF6
C-terminal region of 1 subdomain: Arg138 donates a hydrogen bond to the phenolic O atom of PLP, Arg224 donates a hydrogen bond to the pyridinyl N atom of PLP, Lys41 forms an aldimine linkage with the PLP, eliminating water to form the Schiff base, C-terminal atoms of second subunit Ser209, Gly226 and Ile227 stabilize the PLP phosphate with the help of Ser209 O(gamma), Tyr45 O(eta) and Tyr359 O(eta)
pyridoxal 5'-phosphate
once per 1 million turnovers of racemization a H-atom is added to C4-atom of the substrate moiety of the anionic intermediate instead of the reprotonation of the abstracted hydrogen at C(alpha) resulting in pyridoxamine 5'-phosphate
pyridoxal 5'-phosphate
-
stabilizes anionic intermediate after abstraction of alpha-hydrogen of the substrate amino acid by forming a quinoid intermediate
pyridoxal 5'-phosphate
-
stabilizes anionic intermediate after abstraction of alpha-hydrogen of the substrate amino acid by forming a quinoid intermediate
pyridoxal 5'-phosphate
-
stabilizes anionic intermediate after abstraction of alpha-hydrogen of the substrate amino acid by forming a quinoid intermediate
pyridoxal 5'-phosphate
PLP is bound to the enzyme, adding PLP during developement of enzyme or to an assay is not necessary
pyridoxal 5'-phosphate
-
PLP is inherently bound to the enzyme, removal of PLP inactivates the enzyme, adding PLP restores the activity, addition of 10 microM PLP to native enzyme slightly enhances activity
pyridoxal 5'-phosphate
dependent on, alanine racemase requires pyridoxal-5'-phosphate as a cofactor to form a Schiff base between pyridoxal 5'-phosphate and epsilon-amino group of the lysine residue in the active site
pyridoxal 5'-phosphate
dependent on, pyridoxal 5'-phosphate is bound to each monomer of the dimeric enzyme and forms a Schiff base with Lys39
pyridoxal 5'-phosphate
-
PLP, dependent on
pyridoxal 5'-phosphate
PLP, dependent on, binding structure analysis: the phosphate group of the pyridoxal 5'-phosphate is stabilized by hydrogen bonds with the side chains of Tyr50, Ser222 and Tyr374, and with the backbone of Gly239, Ser222, and Ile240. The pyridine ring of the PLP is stabilized by a hydrogen bond between the N-1 of the cofactor and Nepsilon of Arg237. The C2A of the PLP also interacts with oxygen Q1 of the carboxylated Lys141. All residues stabilizing the PLP cofactor (Tyr50, Ser222, Gly239, Ile240, Arg237, Tyr374) are conserved among Alr proteins. But the AlrSco lacks one important hydrogen bond between Arg148 and the phenolic oxygen of the PLP molecule
pyridoxal 5'-phosphate
-
PLP, dependent on, enzyme-cofactor complex structure, with inhibitor acetate, PDB ID 1SFT
pyridoxal 5'-phosphate
PLP, dependent on, no catalytic enzyme activity without, the apoenzyme activity is completely inhibited
pyridoxal 5'-phosphate
PLP, dependent on. The PLP-binding motif containing the catalytic Lys34 (sequence SMVKANAYGHG) is largely conserved between the various enzymes. The essential PLP cofactor is covalently bound to Lys34 via an internal aldimine linkage and extends towards the centre of the alpha/beta-barrel. The pyridine N1 of the PLP ring is stabilized by hydrogen bonding to Arg209, which is further stabilized by interactions with His159. The phosphate tail of PLP is stabilized by several residues from one monomer. The OP1 of the phosphate group hydrogen bonds to Ile212 and Tyr38, OP2 hydrogen bonds to Try341 and OP3 hydrogen bonds to Ile212 and Ser190. Arg132 is not within hydrogen-bonding distance of PLP in the AlrAba structure
pyridoxal 5'-phosphate
PLP, the PLP content of the enzyme is determined by a spectroscopic method
additional information
-
exogenous pyridoxal 5’-phosphate is not required, but enzyme may be pyridoxal 5’-phosphate-dependent
-
additional information
there is no additional density in the AlrAba structure consistent with the presence of any additional ligands besides pyridoxal 5'-phosphate
-
additional information
-
there is no additional density in the AlrAba structure consistent with the presence of any additional ligands besides pyridoxal 5'-phosphate
-
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Cu2+
enhances the catalytic activity up to 300%
additional information
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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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
-
(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
-
-
2-(4,6-dimethyl-3-oxo-[1,2]thiazolo[5,4-b]pyridin-2-yl)-N-[2-(4-ethoxyphenyl)ethyl]acetamide
-
-
2-N',2-N',7-N',7-N'-tetramethyl-9H-fluorene-2,7-disulfonohydrazide
-
-
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
-
-
6-O-[3-chloro-4-(6-methoxycarbonylpyridine-2-carbonyl)oxyphenyl] 2-O-methyl pyridine-2,6-dicarboxylate
-
-
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
-
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
-
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
-
(2S)-1-oxo-1-([(1R)-1-phosphonoethyl]amino)propan-2-yl L-methioninate
-
-
(2S)-1-oxo-1-([(1R)-1-phosphonoethyl]amino)propan-2-yl L-methioninate
-
(2S)-1-oxo-1-([(1R)-1-phosphonoethyl]amino)propan-2-yl L-methioninate
-
-
(2S)-1-oxo-1-([(1R)-1-phosphonoethyl]amino)propan-2-yl L-methioninate
-
-
(2S)-1-oxo-1-[[(1R)-1-phosphonoethyl]amino]propan-2-yl L-methioninate
-
-
(2S)-1-oxo-1-[[(1R)-1-phosphonoethyl]amino]propan-2-yl L-methioninate
-
-
(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
-
-
(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
-
-
(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
-
-
(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
-
-
(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
-
-
2-(2-chloro-4-nitrophenyl)-4-(2,3-dihydro-1H-inden-2-yl)-1,2,4-thiadiazolidine-3,5-dione
-
-
2-(2-chloro-4-nitrophenyl)-4-(cyclopropylmethyl)-1,2,4-thiadiazolidine-3,5-dione
-
-
2-(2-chloro-4-nitrophenyl)-4-(cyclopropylmethyl)-1,2,4-thiadiazolidine-3,5-dione
-
-
2-(2-chloro-6-methylphenyl)-4-(cyclopropylmethyl)-1,2,4-thiadiazolidine-3,5-dione
-
-
2-(2-chloro-6-methylphenyl)-4-(cyclopropylmethyl)-1,2,4-thiadiazolidine-3,5-dione
-
-
2-(3,5-dimethyl-1,2-oxazol-4-yl)-4-(4-fluorophenyl)-1,2,4-thiadiazolidine-3,5-dione
-
-
2-(3,5-dimethyl-1,2-oxazol-4-yl)-4-(4-fluorophenyl)-1,2,4-thiadiazolidine-3,5-dione
-
-
2-(3-chloro-4-fluorophenyl)-4-(2,3-dihydro-1H-inden-2-yl)-1,2,4-thiadiazolidine-3,5-dione
-
-
2-(3-chloro-4-fluorophenyl)-4-(2,3-dihydro-1H-inden-2-yl)-1,2,4-thiadiazolidine-3,5-dione
-
-
4-(2,3-dihydro-1H-inden-2-yl)-2-[(3-ethylphenyl)methyl]-1,2,4-thiadiazolidine-3,5-dione
-
-
4-(2,3-dihydro-1H-inden-2-yl)-2-[(3-ethylphenyl)methyl]-1,2,4-thiadiazolidine-3,5-dione
-
-
4-(cyclopropylmethyl)-2-(3,5-dimethyl-1,2-oxazol-4-yl)-1,2,4-thiadiazolidine-3,5-dione
-
-
4-(cyclopropylmethyl)-2-(3,5-dimethyl-1,2-oxazol-4-yl)-1,2,4-thiadiazolidine-3,5-dione
-
-
4-(cyclopropylmethyl)-2-[2-(trifluoromethyl)phenyl]-1,2,4-thiadiazolidine-3,5-dione
-
-
4-(cyclopropylmethyl)-2-[2-(trifluoromethyl)phenyl]-1,2,4-thiadiazolidine-3,5-dione
-
-
4-[4-(propan-2-yl)phenyl]-2-[4-[(trifluoromethyl)sulfanyl]phenyl]-1,2,4-thiadiazolidine-3,5-dione
-
-
4-[4-(propan-2-yl)phenyl]-2-[4-[(trifluoromethyl)sulfanyl]phenyl]-1,2,4-thiadiazolidine-3,5-dione
-
-
acetate
-
enzyme-inhibitor complex structure, with pyridoxyl 5'-phosphate, PDB ID 1SFT
alafosfalin
-
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
-
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
-
nucleophilic attack of Lys38 on the electrophilic beta-difluoro-alpha,beta-unsaturated imine
beta,beta,beta-trifluoroalanine
-
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
-
effective in the inhibition of bacterial growth
beta-chloro-L-alanine
-
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
-
enantiomers of beta-chloroalanine as Alr inhibitors
cycloserine
-
8 microg/ml bacterial culture extract markedly inhibits alanine racemase
cycloserine
D-cycloserine or a racemic mixture of D- and L-cycloserine
D-cycloserine
-
importance of N2-structural site in cyloserine for bioactivity
D-cycloserine
active site bound inhibitor, binding structure, overview
D-cycloserine
-
importance of N2-structural site in cyloserine for bioactivity
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
D-cycloserine
model for inactivation mechanism via geminal diamine and ketimine to isoxazole
D-cycloserine
-
mechanism of inactivation and comparison with inactivation of Streptomyces lavendulae enzyme
D-cycloserine
-
importance of N2-structural site in cyloserine for bioactivity
D-cycloserine
-
importance of N2-structural site in cyloserine for bioactivity
D-cycloserine
-
importance of N2-structural site in cyloserine for bioactivity
D-cycloserine
-
importance of N2-structural site in cyloserine for bioactivity
D-cycloserine
specific inhibition is reversible by D-alanine in the growth medium
D-cycloserine
-
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
-
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
-
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
-
mechanism of inactivation and comparison with inactivation of Streptomyces lavendulae enzyme
L-Cycloserine
-
importance of N2-structural site in cyloserine for bioactivity
L-Cycloserine
competitive inhibition, importance of N2-structural site in cyloserine for bioactivity
L-Cycloserine
-
competitive inhibitor, importance of N2-structural site in cyloserine for bioactivity
L-Cycloserine
-
mechanism of inactivation and comparison with inactivation of Bacillus stearothermophilus enzyme
L-leucyl-N-[(1R)-1-phosphonoethyl]-L-alaninamide
-
-
N2-(2-aminodecanoyl)-N-[(1R)-1-phosphonoethyl]-L-alaninamide
-
-
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
-
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
-
propionate influences both Km (affinity for substrate) and Vmax (enzyme catalysis)
pyridoxal 5'-phosphate
-
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
-
additional information
the enzyme activity is not sensitive to the metal chelating agent EDTA indicating that divalent cations are not required for enzyme activity
-
additional information
-
no inhibition by O-carbamoyl-L-serine
-
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
-
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
-
additional information
-
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
-
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
-
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
-
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
-
additional information
-
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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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
pyridoxal 5'-phosphate
-
0.02 mM, activation to 108% of control in the direction of D-Ala formation, activation to 124% of control in the direction of L-Ala formation
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), enzyme residue A131 mediates the activation and stabilization of enzyme ALR by short chain carboxylates
-
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), enzyme residue A131 mediates the activation and stabilization of enzyme ALR by short chain carboxylates
-
additional information
-
activated in presence of monovalent anions including Cl-
-
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
18
D-Lysine
pH 8.0, 30°C, recombinant mutant I222T/Y354W
32
L-lysine
pH 8.0, 30°C, recombinant mutant I222T/Y354W
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
0.89
D-alanine
pH not specified in the publication, 30°C, recombinant enzyme
1.008
D-alanine
+/-0.069, Alr wildtype, 30°C, pH 8.0, spectrophotometrically measured at 340 nm
2.8
D-alanine
pH 8.0, 30°C, recombinant wild-type enzyme
4
D-alanine
pH 8.0, 30°C, recombinant mutant I222T/Y354W
5.4
D-alanine
pH 8.5, temperature not specified in the publication, recombinant mutant K271T
6.1
D-alanine
-
in 50 mM potassium phosphate buffer pH 7.4, at 30°C
7
D-alanine
pH 8.5, temperature not specified in the publication, recombinant wild-type enzyme
15.36
D-alanine
recombinant His-tagged wild-type enzyme, pH and temperature not specified in the publication
20.16
D-alanine
pH 11.0, 70°C, recombinant enzyme
20.78
D-alanine
pH 10.5, 40°C, recombinant wild-type enzyme
52
D-alanine
pH 10.0, 65°C, recombinant mutant Q360Y
58.5
D-alanine
pH 10.0, 65°C, recombinant mutant S173D/Q360Y
110.3
D-alanine
pH 10.0, 65°C, recombinant mutant Q360I
160.9
D-alanine
pH 10.0, 65°C, recombinant mutant S173D
216.1
D-alanine
pH 10.0, 65°C, recombinant mutant Q360W
381.2
D-alanine
pH 10.0, 65°C, recombinant wild-type enzyme
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
2.77
L-alanine
pH not specified in the publication, 30°C, recombinant enzyme
3.03
L-alanine
+/-0.114, Alr D164A, 30°C, pH 8.0, spectrophotometrically measured at 340 nm