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Information on EC 5.1.1.11 - phenylalanine racemase (ATP-hydrolysing) and Organism(s) Brevibacillus brevis and UniProt Accession P0C062
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5.1.1.11 phenylalanine racemase (ATP-hydrolysing)Specify your search results
Word Map
- 5.1.1.11
- brevis
-
racemization
-
nonribosomal
- adenylate
- thioester
-
three-domain
- synthetases
-
decapeptide
-
aminoacyl
-
epimerization
-
nagano
-
triphosphate-dependent
-
single-turnover
-
non-producing
-
diester
- d-phe
-
equilibrate
-
thiolation
- 4'-phosphopantetheine
-
phenylalanyl
- synthesis
The taxonomic range for the selected organisms is: Brevibacillus brevis
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota
Synonyms
pheate, phenylalanine racemase, gramicidin s synthetase i, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
Gramicidin S synthetase I
-
-
-
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GS I
-
-
-
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Phenylalanine racemase
-
-
-
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Phenylalanine racemase (adenosine triphosphate-hydrolyzing)
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-
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Phenylalanine racemase (ATP-hydrolyzing)
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-
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Racemase, phenylalanine (adenosine triphosphate-hydrolyzing)
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-
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
ATP + L-phenylalanine + H2O = AMP + diphosphate + D-phenylalanine
the enzyme activates both L-Phe and D-Phe to form L-phenylalanyl adenylate and D-phenylalanyl adenylate bound to the enzyme, respectively, and then transfers the L-Phe and D-Phe moiety to the thiol group of the enzyme followed by conversion of its configuration, the D-isomer being the more favorable configuration
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ATP + L-phenylalanine + H2O = AMP + diphosphate + D-phenylalanine
racemizes Phe in the thioester-bound stage
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ATP + L-phenylalanine + H2O = AMP + diphosphate + D-phenylalanine
phenylalanine racemase catalyzes the exchange between a proton in the medium and alpha-hydrogen of Phe. Probably a sulfhydryl group, on the enzyme functions as proton donor and acceptor during the reaction
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ATP + L-phenylalanine + H2O = AMP + diphosphate + D-phenylalanine
the amino group of Phe is essential for its binding to the aminoacyl adenylate reaction center. The carbonyl group is not at all or only weakly bound. The benzene ring of Phe which determines substrate recognition also seems to be of minor importance for substrate binding
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
racemization
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-
-
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PATHWAY SOURCE
PATHWAYS
BRENDA
SYSTEMATIC NAME
IUBMB Comments
phenylalanine racemase (ATP-hydrolysing)
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CAS REGISTRY NUMBER
COMMENTARY
37290-95-2
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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
additional information
?
-
-
the enzyme catalyzes Phe racemization and activation. Catalyzes ATP-AMP exchange reaction, L-Phe dependent ATP-AMP exchange reaction
-
-
?
ATP + L-Phe + H2O
AMP + diphosphate + D-Phe
-
equilibrium ratio of L-Phe to D-Phe is 3:7
-
?
ATP + L-phenylalanine + H2O
?
-
phenylalanine racemase, i.e. gramicidin-S synthetase 1, activates and transfers D-Phe to the heavy enzyme, gramicidin S-synthetase 2, which activates the other constituent amino acids on the thioester template
-
-
?
ATP + L-phenylalanine + H2O
?
-
phenylalanine racemase, the light component of gramicidin S synthetase, racemizes Phe and activates it to the aminoacyl adenylate and in a second step to the thioester
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-
?
ATP + L-phenylalanine + H2O
AMP + diphosphate + D-phenylalanine
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there are three activated intermediates: L-phenylalanyl-adenosine-5'-monophosphate diester, L-Phe-S-4'-phosphopantetheine and D-Phe-S-4'-phosphopantetheine-acyl enzyme
-
?
ATP + L-phenylalanine + H2O
AMP + diphosphate + D-phenylalanine
-
the three-domain initiation module PheATE of gramicidin S synthetase catalyzes the activation, thiolation and epimerization of L-phenylalanine, the first amino acid incorporated into the decapeptide antibiotic gramicidin S
-
?
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
ATP + L-phenylalanine + H2O
AMP + diphosphate + D-phenylalanine
-
the three-domain initiation module PheATE of gramicidin S synthetase catalyzes the activation, thiolation and epimerization of L-phenylalanine, the first amino acid incorporated into the decapeptide antibiotic gramicidin S
-
?
ATP + L-phenylalanine + H2O
?
-
phenylalanine racemase, i.e. gramicidin-S synthetase 1, activates and transfers D-Phe to the heavy enzyme, gramicidin S-synthetase 2, which activates the other constituent amino acids on the thioester template
-
-
?
ATP + L-phenylalanine + H2O
?
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phenylalanine racemase, the light component of gramicidin S synthetase, racemizes Phe and activates it to the aminoacyl adenylate and in a second step to the thioester
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-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
4'-phosphopantetheine
-
a 4'-phosphopantetheine carrier is found to be attached to the active site Ser of the consensus motif LGGDSI forming the thiolation site of Phe
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Mg2+
-
Mn2+ or Mg2+ required, up to 0.5 mM. Inhibitory at higher concentrations
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
5,5'-dithiobis(2-nitrobenzoate)
-
presence of ATP, MgCl2, and dithiothreitol prevent rapid sulfhydryl modification. With the enzyme of a gramicidin S non-producing and phenylalanine racemization-lacking mutant the substrate protection against rapid sulfhydryl modification is not detected
cystamine
-
Mg2+ alone or in combination with the substrates ATP and Phe causes significant protection. Cystamine-inactivated enzyme can be reactivated by treatment with dithioerythritol or other sulfhydryl compounds. 0.5 M cystamine causes 90%, 40% and 30% loss in activity if preincubated at 37°C, 20°C, or 0°C for 20 min
Phenylglyoxal
-
inhibition of Phe activation. Both ATP and Phe prevent the inactivation. ATP is competitive with phenylglyoxal, whereas Phe is not. A single arginine residue of GS 1 is essential for Phe activation in binding the phosphate moiety of ATP
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
dithiothreitol
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stimulates 2-2.5fold at 0.05 M. Inhibition at higher concentrations
dithiothreitol
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the velocity of the D-Phe formation from the L-isomer is markedly affected by the concentration of DTT, whereas that of L-Phe formation from the D-isomer is less affected
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
-
temperature dependence of Km-values
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
8.2 - 8.5
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.2 - 8.6
-
7.2: about 25% of maximal activity, 8.6: about 85% of maximal activity
additional information
-
the velocity of the D-Phe formation from the L-isomer is markedly affected by the concentration of DTT, whereas that of L-Phe formation from the D-isomer is less affected
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
73900
holo-A-PCP-form (GrsA plus peptidyl carrier protein domain), gel-filtration
74200
apo-A-PCP-form (GrsA plus peptidyl carrier protein domain), gel-filtration
100000
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
C60F/C331A/C376S/C473A
named A-PCP(delta-4Cys), Km for L-Phe is increased by 2fold, while the kcat is reduced by 1.5fold
D767S
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mutant enzyme is impaired in approach to D-Phe/L-Phe-S-4'phosphopantetheine equilibrium only for D-Phe to L-Phe direction
E892A
R896A
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mutant enzyme is dramatically impaired in approach to D-Phe/L-Phe-S-4'phosphopantetheine equilibrium from either D-Phe or L-Phe
E892A
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mutant enzyme is dramatically impaired in approach to D-Phe/L-Phe-S-4'phosphopantetheine equilibrium from either D-Phe or L-Phe
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
overexpressed as a C-terminal His6-tag protein in Escherichia coli BL21 (DE3)
mutant genes of gramicidin-S synthetase 1 defective in Phe racemization have the same sequence as the wild type gene. These mutant strains also produce defective gramicidin S synthetase 2, lacking 4'-phosphopantetheine, a prosthetic group of this enzyme. The participation of this group in phenylalanine racemization is suggested
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Adams, E.
Amino acid racemases and epimerases
The Enzymes, 3rd Ed. (Boyer, P. D. , ed. )
6
479-507
1972
Brevibacillus brevis
-
Yamada, M.; Kurahashi, K.
Adenosine triphosphate and pyrophosphate dependent phenylalanine racemase of Bacillus brevis Nagano
J. Biochem.
63
59-69
1968
Brevibacillus brevis
Yamada, M.; Kurahashi, K.
Further purification and properties of adenosine triphosphate-dependent phenylalanine racemase of Bacillus brevis NAGANO
J. Biochem.
66
529-540
1969
Brevibacillus brevis
Vater, J.; Kleinkauf, H.
Gramicidin S synthetase. A further characterization of phenylalanine racemase, the light enzyme of gramicidin S-synthetase
Biochim. Biophys. Acta
429
1062-1072
1976
Brevibacillus brevis
Hori, K.; Saito, F.; Tokita, K.; Kurotsu, T.; Kanda, M.; Saito, Y.
Mutant genes of gramicidin S synthetase 1 defective in phenylalanine racemization have the same sequence as the wild gene
J. Biochem.
116
1202-1204
1994
Brevibacillus brevis
Nguyen Huu, M.C.; von Dungen, A.; Kleinkauf, H.
Irreversible inhibition of the light enzyme of gramicidin S synthetase by halogenomethylketones of phenylalanine
FEBS Lett.
67
75-79
1976
Brevibacillus brevis
Kanda, M.; Hori, K.; Kurotsu, T.; Yamada, Y.; Miura, S.; Saito, Y.
Essential arginine residue in gramicidin S synthetase I of Bacillus brevis
J. Biochem.
91
939-943
1982
Brevibacillus brevis
Vater, J.; Mallow, N.; Gerhardt, S.; Kleinkauf, H.
The temperature dependence of the partial processes involved in the biosynthesis of gramicidin S
Pept. Antibiot.
1982
219-230
1982
Brevibacillus brevis
-
Vater, J.; Mallow, N.; Gerhardt, S.; Gadow, A.; Kleinkauf, H.
Gramicidin S synthetase. Temperature dependence and thermodynamic parameters of substrate amino acid activation reactions
Biochemistry
24
2022-2027
1985
Brevibacillus brevis
Schroeter-Kermani, C.; von Dhren, H.; Kleinkauf, H.
Active thiol-directed binding and adsorption of gramicidin S-synthetase I to disulfide-containing matrices
Biochim. Biophys. Acta
883
345-352
1986
Brevibacillus brevis
-
Schlunsen, J.; Manecke, G.
Spezifische Adsorbentien fur das Peptidantibiotika synthetisierende Enzymsystem Gramicidin S Synthetase, 1. Darstellung niedermolekularer Spacer-Ligand-Verbindungen
Makromol. Chem.
188
3005-3016
1987
Brevibacillus brevis
-
Kambe, M.; Imae, Y.; Kurahashi, K.
Biochemical studies on gramicidin S non-producing mutants of Bacillus brevis ATCC 9999
J. Biochem.
75
481-493
1974
Brevibacillus brevis
Kanda, M.; Hori, K.; Kurotsu, T.; Miura, S.; Yamada, Y.; Saito, Y.
Sulfhydryl groups related to the catalytic activity of gramicidin S synthetase 1 of Bacillus brevis
J. Biochem.
90
765-771
1981
Brevibacillus brevis
Saito, Y.
Some characteristics of gramicidin S-synthetase obtained from mutants of Bacillus brevis which could not form D-phenylalanyl-L-prolyl diketo-piperazine
Pept. Antibiot.
1982
195-207
1982
Brevibacillus brevis
-
Matteo, C.C.; Cooney, C.L.; Demain, A.L.
Production of gramicidin S synthetases by Bacillus brevis in continuous culture
J. Gen. Microbiol.
96
415-422
1976
Brevibacillus brevis
Takahashi, H.; Sato, E.; Kurahashi, K.
Racemization of phenylalanine by adenosine triphosphate-dependent phenylalanine racemase of Bacillus brevis Nagano
J. Biochem.
69
973-976
1971
Brevibacillus brevis
Kanda, M.; Hori, K.; Kurotsu, T.; Miura, S.; Saito, Y.
Reaction mechanism of gramicidin S synthetase 1, phenylalanine racemase, of Bacillus brevis
J. Biochem.
105
653-659
1989
Brevibacillus brevis
Stein, T.; Kluge, B.; Vater, J.; Franke, P.; Otto, A.; Wittmann-Liebold, B.
Gramicidin S synthetase 1 (phenylalanine racemase), a prototype of amino acid racemase containing the cofactor 4'-phosphopantetheine
Biochemistry
34
4633-4642
1995
Brevibacillus brevis
Vater, J.; Schlumbohm, W.; Salnikow, J.; Irrgang, K.D.; Miklus, M.; Choli, T.; Kleinkauf, H.
Proteinchemical and kinetic features of gramicidin S synthetase
Biol. Chem. Hoppe-Seyler
370
1013-1018
1989
Brevibacillus brevis
Stachelhaus, T.; Walsh, C.T.
Mutational analysis of the epimerization domain in the initiation module PheATE of gramicidin S synthetase
Biochemistry
39
5775-5787
2000
Brevibacillus brevis
Luo, L.; Walsh, C.T.
Kinetic analysis of three activated phenylalanyl intermediates generated by the initiation module PheATE of gramicidin S synthetase
Biochemistry
40
5329-5337
2001
Brevibacillus brevis
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