Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
2'-methyl-(2S)-alpha-phenylalanine
2'-methyl-beta-phenylalanine
-
plus about 2% of 2'-methyl-(E)-cinnamate
-
?
2-fluoro-L-phenylalanine
(S)-3-amino-3-(2-fluorophenyl)propanoic acid
-
-
-
?
2-methoxy-L-phenylalanine
(S)-3-amino-3-(2-methoxyphenyl)propanoic acid
-
-
-
?
2-methyl-L-phenylalanine
(S)-3-amino-3-(o-tolyl)propanoic acid
-
-
-
?
3-bromo-L-phenylalanine
(S)-3-amino-3-(3-bromophenyl)propanoic acid
-
-
-
?
3-chloro-L-phenylalanine
(S)-3-amino-3-(3-chlorophenyl)propanoic acid
-
-
-
?
3-fluoro-L-phenylalanine
(S)-3-amino-3-(3-fluorophenyl)propanoic acid
-
-
-
?
3-furan-2-yl-L-phenylalanine
(S)-3-amino-3-(furan-2-yl)propanoic acid
-
-
-
?
3-methoxy-L-phenylalanine
(S)-3-amino-3-(3-methoxyphenyl)propanoic acid
-
-
-
?
3-methyl-L-phenylalanine
(S)-3-amino-3-(3-methylphenyl)propanoic acid
-
-
-
?
3-nitro-L-phenylalanine
(S)-3-amino-3-(3-nitrophenyl)propanoic acid
-
-
-
?
3-thiophen-2-yl-L-phenylalanine
(S)-3-amino-3-(thiophen-2-yl)propanoic acid
-
-
-
?
3-thiophen-3-yl-L-phenylalanine
(S)-3-amino-3-(thiophen-3-yl)propanoic acid
-
-
-
?
4-bromo-L-phenylalanine
(S)-3-amino-3-(4-bromophenyl)propanoic acid
-
-
-
?
4-chloro-L-phenylalanine
(S)-3-amino-3-(4-chlorophenyl)propanoic acid
-
-
-
?
4-fluoro-L-phenylalanine
(S)-3-amino-3-(4-fluorophenyl)propanoic acid
-
-
-
?
4-methoxy-L-phenylalanine
(S)-3-amino-3-(4-methoxyphenyl)propanoic acid
-
-
-
?
4-methyl-L-phenylalanine
(S)-3-amino-3-(4-methylphenyl)propanoic acid
-
-
-
?
4-nitro-L-phenylalanine
(S)-3-amino-3-(4-nitrophenyl)propanoic acid
-
-
-
?
D-alpha-phenylalanine
D-beta-phenylalanine
(S)-alpha-phenylalanine
-
-
?
D-beta-phenylalanine
L-phenylalanine
D-phenylalanine
D-beta-phenylalanine
-
-
-
?
L-phenylalanine
(S)-3-amino-3-phenylpropanoic acid
-
-
-
?
L-phenylalanine
D-beta-phenylalanine
L-phenylalanine
L-beta-phenylalanine
-
when L-Phe enters the active site, the carboxylate group forms a bidentate salt bridge with residue R325. The carboxylate group further interacts with residue Q319. The amine group and the pro-3S hydrogen atom are oriented in an anti-periplanar geometry suitable for the elimination step. A nucleophilic attack of the amine group of the substrate on the 4-methylideneimidazole-5-one cofactor group preceeds abstraction of the proton by the general base Y80, possibly assisted by another basic group, and elimination of 4-methylideneimidazole-5-one-NH2. This leads to formation of trans-cinnamic acid, with the carboxylate group still bound to residue R325. The next step is the readdition of 4-methylideneimidazole-5-one-NH2 to the beta-position and of the proton to the alpha-position. This step requires exposure of the Re face of Cbeta to the 4-methylideneimidazole-5-one-NH2 and the carboxylate group to function as a good electron sink
-
r
rac-2-chloro-phenylalanine
2-chloro-D-beta-phenylalanine + 2-chloro-L-beta-phenylalanine
-
-
-
?
rac-2-fluoro-phenylalanine
2-fluoro-D-beta-phenylalanine + 2-fluoro-L-beta-phenylalanine
-
-
-
?
rac-2-nitro-phenylalanine
2-nitro-D-beta-phenylalanine + 2-nitro-L-beta-phenylalanine
-
-
-
?
rac-3-chloro-phenylalanine
3-chloro-D-beta-phenylalanine + 3-chloro-L-beta-phenylalanine
-
-
-
?
rac-3-fluoro-phenylalanine
3-fluoro-D-beta-phenylalanine + 3-fluoro-L-beta-phenylalanine
-
-
-
?
rac-3-nitro-phenylalanine
3-nitro-D-beta-phenylalanine + 3-nitro-L-beta-phenylalanine
-
-
-
?
rac-4-bromo-phenylalanine
4-bromo-D-beta-phenylalanine + 4-bromo-L-beta-phenylalanine
-
-
-
?
rac-4-chloro-phenylalanine
4-chloro-D-beta-phenylalanine + 4-chloro-L-beta-phenylalanine
-
-
-
?
rac-4-fluoro-phenylalanine
4-fluoro-D-beta-phenylalanine + 4-fluoro-L-beta-phenylalanine
-
-
-
?
rac-4-nitro-phenylalanine
4-nitro-D-beta-phenylalanine + 4-nitro-L-beta-phenylalanine
-
-
-
?
rac-alpha-phenylalanine
D-beta-phenylalanine
-
-
-
?
rac-thiophen-2-ylalanine
D-beta-thiophen-2-ylalanine + L-beta-thiophen-2-ylalanine
-
-
-
?
additional information
?
-
D-beta-phenylalanine
L-phenylalanine
-
-
-
r
D-beta-phenylalanine
L-phenylalanine
-
-
-
r
L-phenylalanine
D-beta-phenylalanine
-
-
-
?
L-phenylalanine
D-beta-phenylalanine
-
-
-
?
L-phenylalanine
D-beta-phenylalanine
-
-
-
?
L-phenylalanine
D-beta-phenylalanine
-
-
-
r
L-phenylalanine
D-beta-phenylalanine
-
plus trans-cinnamate. At steady state, enzyme converts (S)-alpha-phenylalanine to (S)-beta-phenylalanine/transcinnamate in a 90:10 ratio
-
?
L-phenylalanine
D-beta-phenylalanine
the NH2 and pro-(3S) hydrogen groups at Calpha and Cbeta, respectively, of the substrate are removed and interchanged completely intramolecularly with inversion of configuration at the migration centers to form beta-phenylalanine
-
-
?
L-phenylalanine
D-beta-phenylalanine
-
-
-
r
additional information
?
-
enzyme additionally displays ammonia lyase activity, EC. 4.3.1.24, catalyzing the elimination of ammonia from L-phenylalanine to give trans-cinnamate. No trans-cinnamate is produced upon incubation with L-phenylalanine at 25°C, whilst very low lyase activity can be observed at 30°C
-
-
?
additional information
?
-
enzyme reacts by an alkylamine elimination pathway, which involves covalent attachment between the amino group of the substrate and the product as well as the 4-methylidene-1H-imidazol-5(4H)-one cofactor
-
-
?
additional information
?
-
in nature, phenylalanine 2,3-aminonutase from Pantoea agglomerans is an (S)-selective enzyme, transforming the (S)-alpha-phenylalanine in (S)-beta-phenylalanine
-
-
?
additional information
?
-
enzyme substrate specificity, detailed overview. Interactions the most significant are between the substrates and residues Phe428, Val108, Leu421, Leu104, Gln456, and Tyr. Electronic effects of ortho-, para-, and meta-substituents. The enzyme produces a different amount of cinnamate as side-product dependent on the substrate, e.g. the product pool catalyzed by PaPAM from 13 contains more cinnamate analogue (21.7%) compared to that made from other m-substituted substrates 3-bromo-L-phenylalanine, 3-chloro-L-phenylalanine, 3-nitro-L-phenylalanine, and 3-methoxy-L-phenylalanine that contain between 1.0% and 7.4%. Relationship between PaPAM-substrate interaction energies, flexibility, and Km. Compounds 2-bromo-L-phenylalanine, 2-chloro-L-phenylalanine, and 2-nitro-L-phenylalanine are no substrates
-
-
?
additional information
?
-
PaPAM converts (S)-alpha-amino acids to (S)-beta-amino acids
-
-
?
additional information
?
-
the enzyme performs enantiomer-selective isomerization of various racemic alpha- and beta-arylalanines, both alpha- and beta-arylalanines are accepted as substrates when the aryl moiety is relatively small, like phenyl, 2-, 3-, 4-fluorophenyl or thiophen-2-yl. While 2-substituted alpha-phenylalanines bearing bulky electron withdrawing substituents do not react, the corresponding substituted beta-aryl analogues are converted rapidly. Conversion of 3- and 4-substituted alpha-arylalanines happens smoothly, while conversion of the corresponding beta-arylalanines is poor or non-existent. The high enantiomeric excess (ee) values of the products indicate excellent enantiomer selectivity and stereospecificity of the isomerization except for (S)-2-nitro-a-phenylalanine (ee 92%) from the beta-isomer. Computational modelling reveals that one of the main factors controlling biocatalytic activity is the energy difference between the covalent regioisomeric enzyme-substrate complexes. Formation of significant amounts of (E)-arylacrylates is observed with many substrates indicating substantial lyase-activity of enzyme PaPAM. Differences of conversions of the PaPAM-catalysed isomerizations from alpha- and beta-arylalanines racemates, substrate categories and relative energy differences of the regioisomeric N-MIO intermediates, substrate specificity and reaction products, overview
-
-
?
additional information
?
-
enzyme additionally displays ammonia lyase activity, EC. 4.3.1.24, catalyzing the elimination of ammonia from L-phenylalanine to give trans-cinnamate. No trans-cinnamate is produced upon incubation with L-phenylalanine at 25°C, whilst very low lyase activity can be observed at 30°C
-
-
?
additional information
?
-
-
the recombinant enzyme displays a broad substrate spectrum
-
-
?
additional information
?
-
enzyme additionally displays ammonia lyase activity, EC. 4.3.1.24, catalyzing the elimination of ammonia from L-phenylalanine to give trans-cinnamate
-
-
?
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
0.073
2-fluoro-L-phenylalanine
pH 8.0, 31°C, recombinant enzyme
0.164
2-methoxy-L-phenylalanine
pH 8.0, 31°C, recombinant enzyme
0.088
2-methyl-L-phenylalanine
pH 8.0, 31°C, recombinant enzyme
0.339
3-bromo-L-phenylalanine
pH 8.0, 31°C, recombinant enzyme
0.432
3-chloro-L-phenylalanine
pH 8.0, 31°C, recombinant enzyme
0.027
3-fluoro-L-phenylalanine
pH 8.0, 31°C, recombinant enzyme
0.415
3-furan-2-yl-L-phenylalanine
pH 8.0, 31°C, recombinant enzyme
0.99
3-methoxy-L-phenylalanine
pH 8.0, 31°C, recombinant enzyme
0.204
3-methyl-L-phenylalanine
pH 8.0, 31°C, recombinant enzyme
0.43
3-nitro-L-phenylalanine
pH 8.0, 31°C, recombinant enzyme
0.132
3-thiophen-2-yl-L-phenylalanine
pH 8.0, 31°C, recombinant enzyme
0.337
3-thiophen-3-yl-L-phenylalanine
pH 8.0, 31°C, recombinant enzyme
0.525
4-bromo-L-phenylalanine
pH 8.0, 31°C, recombinant enzyme
0.491
4-chloro-L-phenylalanine
pH 8.0, 31°C, recombinant enzyme
0.029
4-fluoro-L-phenylalanine
pH 8.0, 31°C, recombinant enzyme
1.187
4-methoxy-L-phenylalanine
pH 8.0, 31°C, recombinant enzyme
0.163
4-methyl-L-phenylalanine
pH 8.0, 31°C, recombinant enzyme
0.752
4-nitro-L-phenylalanine
pH 8.0, 31°C, recombinant enzyme
0.027 - 0.04
D-beta-phenylalanine
0.022 - 0.168
L-phenylalanine
additional information
additional information
Michaelis-Menten kinetics
-
0.027
D-beta-phenylalanine
25°C, pH not specified in the publication
0.04
D-beta-phenylalanine
25°C, pH not specified in the publication
0.022
L-phenylalanine
25°C, pH not specified in the publication
0.032
L-phenylalanine
25°C, pH not specified in the publication
0.05
L-phenylalanine
pH not specified in the publication, temperature not specified in the publication
0.168
L-phenylalanine
pH 8.0, 31°C
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
0.022
2-fluoro-L-phenylalanine
pH 8.0, 31°C, recombinant enzyme
0.003
2-methoxy-L-phenylalanine
pH 8.0, 31°C, recombinant enzyme
0.064
2-methyl-L-phenylalanine
pH 8.0, 31°C, recombinant enzyme
0.42
3-bromo-L-phenylalanine
pH 8.0, 31°C, recombinant enzyme
0.484
3-chloro-L-phenylalanine
pH 8.0, 31°C, recombinant enzyme
0.031
3-fluoro-L-phenylalanine
pH 8.0, 31°C, recombinant enzyme
0.236
3-furan-2-yl-L-phenylalanine
pH 8.0, 31°C, recombinant enzyme
0.209
3-methoxy-L-phenylalanine
pH 8.0, 31°C, recombinant enzyme
0.058
3-methyl-L-phenylalanine
pH 8.0, 31°C, recombinant enzyme
0.146
3-nitro-L-phenylalanine
pH 8.0, 31°C, recombinant enzyme
0.026
3-thiophen-2-yl-L-phenylalanine
pH 8.0, 31°C, recombinant enzyme
0.143
3-thiophen-3-yl-L-phenylalanine
pH 8.0, 31°C, recombinant enzyme
0.045
4-bromo-L-phenylalanine
pH 8.0, 31°C, recombinant enzyme
0.053
4-chloro-L-phenylalanine
pH 8.0, 31°C, recombinant enzyme
0.023
4-fluoro-L-phenylalanine
pH 8.0, 31°C, recombinant enzyme
0.022
4-methoxy-L-phenylalanine
pH 8.0, 31°C, recombinant enzyme
0.013
4-methyl-L-phenylalanine
pH 8.0, 31°C, recombinant enzyme
0.038
4-nitro-L-phenylalanine
pH 8.0, 31°C, recombinant enzyme
0.059 - 0.22
D-beta-phenylalanine
0.061 - 0.301
L-phenylalanine
0.059
D-beta-phenylalanine
25°C, pH not specified in the publication
0.22
D-beta-phenylalanine
25°C, pH not specified in the publication
0.061
L-phenylalanine
pH not specified in the publication, temperature not specified in the publication
0.087
L-phenylalanine
25°C, pH not specified in the publication
0.159
L-phenylalanine
25°C, pH not specified in the publication
0.301
L-phenylalanine
pH 8.0, 31°C, recombinant enzyme
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
0.31
2-fluoro-L-phenylalanine
pH 8.0, 31°C, recombinant enzyme
0.02
2-methoxy-L-phenylalanine
pH 8.0, 31°C, recombinant enzyme
0.73
2-methyl-L-phenylalanine
pH 8.0, 31°C, recombinant enzyme
1.24
3-bromo-L-phenylalanine
pH 8.0, 31°C, recombinant enzyme
1.12
3-chloro-L-phenylalanine
pH 8.0, 31°C, recombinant enzyme
1.2
3-fluoro-L-phenylalanine
pH 8.0, 31°C, recombinant enzyme
0.588
3-furan-2-yl-L-phenylalanine
pH 8.0, 31°C, recombinant enzyme
0.21
3-methoxy-L-phenylalanine
pH 8.0, 31°C, recombinant enzyme
0.19
3-methyl-L-phenylalanine
pH 8.0, 31°C, recombinant enzyme
0.34
3-nitro-L-phenylalanine
pH 8.0, 31°C, recombinant enzyme
0.19
3-thiophen-2-yl-L-phenylalanine
pH 8.0, 31°C, recombinant enzyme
0.428
3-thiophen-3-yl-L-phenylalanine
pH 8.0, 31°C, recombinant enzyme
0.09
4-bromo-L-phenylalanine
pH 8.0, 31°C, recombinant enzyme
0.11
4-chloro-L-phenylalanine
pH 8.0, 31°C, recombinant enzyme
0.79
4-fluoro-L-phenylalanine
pH 8.0, 31°C, recombinant enzyme
0.019
4-methoxy-L-phenylalanine
pH 8.0, 31°C, recombinant enzyme
0.082
4-methyl-L-phenylalanine
pH 8.0, 31°C, recombinant enzyme
0.05
4-nitro-L-phenylalanine
pH 8.0, 31°C, recombinant enzyme
2.2 - 5.53
D-beta-phenylalanine
0.051 - 7.19
L-phenylalanine
2.2
D-beta-phenylalanine
25°C, pH not specified in the publication
5.53
D-beta-phenylalanine
25°C, pH not specified in the publication
0.051
L-phenylalanine
pH 8.0, 31°C, recombinant enzyme
1.2
L-phenylalanine
pH not specified in the publication, temperature not specified in the publication
2.73
L-phenylalanine
25°C, pH not specified in the publication
7.19
L-phenylalanine
25°C, pH not specified in the publication
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
physiological function
PaPAM makes the (3S)-beta-phenylalanine antipode on the biosynthetic pathway to the antibiotic andrimid starting from (S)-beta-phenylalanine via (S)-alpha-phenylalanine
evolution
phenylalanine 2,3-mutases, PAMs, belong to the class I lyase-like family that includes tyrosine 2,3-aminomutases (TAMs), tyrosine ammonia-lyases (TALs), and histidine ammonia-lyases (HALs). All these enzymes rely on a protein-derived cofactor, 4-methylideneimidazol-5-one (MIO), which is generated autocatalytically from three active site residues, Ala-Ser-Gly (Thr-Ser-Gly in PaPAM), forming a MIO signature motif
evolution
the enzyme belongs to a class I lyase-like superfamily of catalysts, along with other MIO-dependent aminomutases
malfunction
a hitA knockout mutant shows no hitachimycin production, but antibiotic production is restored by feeding with (S)-beta-Phe
malfunction
-
a hitA knockout mutant shows no hitachimycin production, but antibiotic production is restored by feeding with (S)-beta-Phe
-
metabolism
the enzyme is important in the hitachimycin biosynthetic pathway. A plausible biosynthetic pathway for hitachimycin, including a unique polyketide skeletal transformation mechanism, is proposed
metabolism
-
the enzyme is important in the hitachimycin biosynthetic pathway. A plausible biosynthetic pathway for hitachimycin, including a unique polyketide skeletal transformation mechanism, is proposed
-
additional information
enzyme structure-activity analysis and modeling of substrate-PaPAM structural interactions, overview
additional information
molecular modelling of the covalent enzyme-substrate N-MIO complexes in PaPAM
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Ratnayake, N.D.; Wanninayake, U.; Geiger, J.H.; Walker, K.D.
Stereochemistry and mechanism of a microbial phenylalanine aminomutase
J. Am. Chem. Soc.
133
8531-8533
2011
Pantoea agglomerans, Pantoea agglomerans (Q84FL5)
brenda
Strom, S.; Wanninayake, U.; Ratnayake, N.; Walker, K.; Geiger, J.
Insights into the mechanistic pathway of the Pantoea agglomerans phenylalanine aminomutase
Angew. Chem. Int. Ed. Engl.
51
2898-2902
2012
Pantoea agglomerans (Q84FL5)
brenda
Wu, B.; Szymanski, W.; Wybenga, G.; Heberling, M.; Bartsch, S.; Dewildeman, S.; Poelarends, G.; Feringa, B.; Dijkstra, B.; Janssen, D.
Mechanism-inspired engineering of phenylalanine aminomutase for enhanced beta-regioselective asymmetric amination of cinnamates
Angew. Chem. Int. Ed. Engl.
51
482-486
2012
Taxus chinensis (Q68G84)
brenda
Chesters, C.; Wilding, M.; Goodall, M.; Micklefield, J.
Thermal bifunctionality of bacterial phenylalanine aminomutase and ammonia lyase enzymes
Angew. Chem. Int. Ed. Engl.
51
4344-4348
2012
Pantoea agglomerans (Q84FL5), Streptomyces maritimus (Q9KHJ9)
brenda
Ratnayake, N.; Liu, N.; Kuhn, L.; Walker, K.
Ring-substituted beta-arylalanines for probing substituent effects on the isomerization reaction catalyzed by an aminomutase
ACS Catal.
4
3077-3090
2014
Pantoea agglomerans (Q84FL5)
-
brenda
Zhu, L.; Tao, Y.; Ge, F.; Li, W.; Liu, Y.; Du, G.
Production and characterization of phenylalanine aminomutase from Streptomyces maritimus and synthesis of beta-arylalanine
Chem. J. Chin. Univ.
38
206-211
2017
Streptomyces maritimus
-
brenda
Kudo, F.; Kawamura, K.; Uchino, A.; Miyanaga, A.; Numakura, M.; Takayanagi, R.; Eguchi, T.
Genome mining of the hitachimycin biosynthetic gene cluster involvement of a phenylalanine-2,3-aminomutase in biosynthesis
ChemBioChem
16
909-914
2015
Embleya scabrispora (A0A0F7R1D9), Embleya scabrispora JCM 11712 / DSM 41855 (A0A0F7R1D9)
brenda
Varga, A.; Banoczi, G.; Nagy, B.; Bencze, L.; Tosa, M.; Gellert, A.; Irimie, F.; Retey, J.; Poppe, L.; Paizs, C.
Influence of the aromatic moiety in alpha- and beta-arylalanines on their biotransformation with phenylalanine 2,3-aminomutase from Pantoea agglomerans
RSC Adv.
6
56412-56420
2016
Pantoea agglomerans (Q84FL5)
-
brenda
Varga, A.; Filip, A.; Bencze, L.; Satorhelyi, P.; Bell, E.; Vertessy, B.; Poppe, L.; Paizs, C.
Expression and purification of recombinant phenylalanine 2,3-aminomutase from Pantoea agglomerans
Stud. Univ. Babes-Bolyai Chem.
61
7-19
2016
Pantoea agglomerans (Q84FL5)
-
brenda