We're sorry, but BRENDA doesn't work properly without JavaScript. Please make sure you have JavaScript enabled in your browser settings.
Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
EC Tree
IUBMB Comments Requires Fe2+. Involved in the biosynthesis of the vancomycin group of glycopeptide antibiotics.
The enzyme appears in viruses and cellular organisms
Synonyms
hydroxymandelate synthase, 4-hydroxymandelate synthase, (s)-hydroxymandelate synthase,
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
(S)-hydroxymandelate synthase
4-(S) hydroxymandelate synthase
4-hydroxyphenylpyruvate dioxygenase II
-
-
-
hydroxymandelate synthase
-
-
(S)-hydroxymandelate synthase
-
-
(S)-hydroxymandelate synthase
-
-
4-(S) hydroxymandelate synthase
-
-
4-(S) hydroxymandelate synthase
-
-
HMS
-
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
4-hydroxyphenylpyruvate + O2 = (S)-4-hydroxymandelate + CO2
4-hydroxyphenylpyruvate + O2 = (S)-4-hydroxymandelate + CO2
one oxygen from molecular oxygen is incorporated into the carboxyl group and one into the benzylic hydroxyl group
-
4-hydroxyphenylpyruvate + O2 = (S)-4-hydroxymandelate + CO2
reaction mechanism, overview
-
4-hydroxyphenylpyruvate + O2 = (S)-4-hydroxymandelate + CO2
HMS uses Fe(IV)=O to perform hydroxylation of the benzylic carbon, reaction mechanism with electrophilic attack on the aromatic ring, and HMS catalytic cycle, overview
-
4-hydroxyphenylpyruvate + O2 = (S)-4-hydroxymandelate + CO2
-
-
-
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
oxidative decarboxylation
-
-
-
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.
4-hydroxyphenylpyruvate:oxygen oxidoreductase (decarboxylating)
Requires Fe2+. Involved in the biosynthesis of the vancomycin group of glycopeptide antibiotics.
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-oxo-4-phenylbutanoic acid + O2
?
4-fluorophenylpyruvic acid + O2
?
4-hydroxyphenylpyruvate + O2
4-hydroxymandelate + CO2
4-methoxyphenylpyruvic acid + O2
?
4-methylphenylpyruvic acid + O2
?
-
-
-
?
4-nitrophenylpyruvic acid + O2
?
-
-
-
?
phenylpyruvic acid + O2
?
-
-
-
?
additional information
?
-
2-oxo-4-phenylbutanoic acid + O2
?
-
-
-
?
2-oxo-4-phenylbutanoic acid + O2
?
-
-
-
?
4-fluorophenylpyruvic acid + O2
?
-
-
-
?
4-fluorophenylpyruvic acid + O2
?
-
-
-
?
4-hydroxyphenylpyruvate + O2
4-hydroxymandelate + CO2
-
-
-
?
4-hydroxyphenylpyruvate + O2
4-hydroxymandelate + CO2
-
-
-
?
4-hydroxyphenylpyruvate + O2
4-hydroxymandelate + CO2
-
alpha-keto acid dependent dioxygenase reaction
substrate of non-ribosomal peptide antibiotics such as vancomycin and chloroeremomycin
?
4-hydroxyphenylpyruvate + O2
4-hydroxymandelate + CO2
-
active site structure and 4-hydroxymandelate binding structure, overview
-
?
4-hydroxyphenylpyruvate + O2
4-hydroxymandelate + CO2
-
-
-
?
4-hydroxyphenylpyruvate + O2
4-hydroxymandelate + CO2
-
-
-
?
4-methoxyphenylpyruvic acid + O2
?
-
-
-
?
4-methoxyphenylpyruvic acid + O2
?
-
-
-
?
additional information
?
-
-
substrate specificity, overview, Hms accepts a range of 2-oxo acids, whereby the presence of an aromatic substituent is crucial for efficient substrate turnover. A hydrophobic substrate binding pocket is identified as the likely determinant of substrate specificity. The enzyme shows high regioselectivity of oxygenation and a strong coupling efficiency of C-C bond cleavage and subsequent hydroxylation. The turnover number of Hms strongly correlates with substrate hydrophobicity. Quantitative structure activity relationship and in silico docking analyses, e.g. with (S)-mandelate and (R)-mandelate, overview
-
?
additional information
?
-
-
substrate specificity, overview, Hms accepts a range of 2-oxo acids, whereby the presence of an aromatic substituent is crucial for efficient substrate turnover. A hydrophobic substrate binding pocket is identified as the likely determinant of substrate specificity. The enzyme shows high regioselectivity of oxygenation and a strong coupling efficiency of C-C bond cleavage and subsequent hydroxylation. The turnover number of Hms strongly correlates with substrate hydrophobicity. Quantitative structure activity relationship and in silico docking analyses, e.g. with (S)-mandelate and (R)-mandelate, overview
-
?
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
4-hydroxyphenylpyruvate + O2
4-hydroxymandelate + CO2
4-hydroxyphenylpyruvate + O2
4-hydroxymandelate + CO2
-
-
-
?
4-hydroxyphenylpyruvate + O2
4-hydroxymandelate + CO2
-
-
-
-
?
4-hydroxyphenylpyruvate + O2
4-hydroxymandelate + CO2
-
alpha-keto acid dependent dioxygenase reaction
substrate of non-ribosomal peptide antibiotics such as vancomycin and chloroeremomycin
-
?
4-hydroxyphenylpyruvate + O2
4-hydroxymandelate + CO2
-
-
-
-
?
4-hydroxyphenylpyruvate + O2
4-hydroxymandelate + CO2
-
-
-
-
?
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Fe2+
-
putative FeIV=O species hydroxylates benzylic position
Fe2+
-
a Fe(II)-dependent dioxygenase
Fe2+
-
a nonheme Fe(II) dependent dioxygenase
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
2-[2-nitro-4-(triflouromethyl)benzoyl]-1,3-cyclohexanedione
-
anaerobic conditions, complex with Fe2+ and enzyme, a herbicide/therapeutic that inhibits 4-hydroxyphenylpyruvate dioxygenase in a similar manner
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
0.035
2-oxo-4-phenylbutanoic acid
-
pH 7.5, 25°C
0.0143 - 0.22
4-hydroxyphenylpyruvate
0.16
4-methoxyphenylpyruvic acid
-
pH 7.5, 25°C
0.353
phenylpyruvic acid
-
pH 7.5, 25°C
additional information
additional information
-
steady-state kinetic analysis, overview
-
0.0143
4-hydroxyphenylpyruvate
-
pH 7.0, 25°C, mutant I216N
0.0205
4-hydroxyphenylpyruvate
-
pH 7.0, 25°C, mutant T214P
0.028
4-hydroxyphenylpyruvate
-
pH 7.0, 25°C, mutant S201A
0.0476
4-hydroxyphenylpyruvate
-
pH 7.0, 25°C, wild-type enzyme
0.22
4-hydroxyphenylpyruvate
-
pH 7.5, 25°C
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
0.17
2-oxo-4-phenylbutanoic acid
-
pH 7.5, 25°C
0.077
4-fluorophenylpyruvic acid
-
pH 7.5, 25°C
1.2 - 4.5
4-hydroxyphenylpyruvate
0.96
4-methoxyphenylpyruvic acid
-
pH 7.5, 25°C
0.13
4-methylphenylpyruvic acid
-
pH 7.5, 25°C
0.035
4-nitrophenylpyruvic acid
-
pH 7.5, 25°C
0.88
phenylpyruvic acid
-
pH 7.5, 25°C
1.2
4-hydroxyphenylpyruvate
-
pH 7.0, 25°C, mutant T214P
1.4
4-hydroxyphenylpyruvate
-
pH 7.0, 25°C, mutant I216N
3
4-hydroxyphenylpyruvate
-
pH 7.0, 25°C, mutant S201A
3.7
4-hydroxyphenylpyruvate
-
pH 7.0, 25°C, wild-type enzyme
4.5
4-hydroxyphenylpyruvate
-
pH 7.5, 25°C
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
57.5 - 108
4-hydroxyphenylpyruvate
57.5
4-hydroxyphenylpyruvate
-
pH 7.0, 25°C, mutant T214P
77
4-hydroxyphenylpyruvate
-
pH 7.0, 25°C, wild-type enzyme
98.5
4-hydroxyphenylpyruvate
-
pH 7.0, 25°C, mutant I216N
108
4-hydroxyphenylpyruvate
-
pH 7.0, 25°C, mutant S201A
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.
25
-
assay at
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
-
-
-
brenda
-
-
-
brenda
-
-
-
brenda
gene AOHMS
-
-
brenda
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
evolution
-
4-hydroxyphenylpyruvate dioxygenase, HPPD, EC 1.13.11.27, and hydroxymandelate synthase catalyze similar reactions using the same substrates, 4-hydroxyphenylpyruvate and dioxygen. Initially, both enzymes reduce and activate dioxygen in order to decarboxylate 4-hydroxyphenylpyruvate, yielding 4-hydroxyphenylacetate, CO2, and an activated oxo intermediate. Both enzymes then hydroxylate 4-hydroxyphenylacetate but do so in different positions
additional information
-
molecular docking and modeling, molecular dynamics and simulations by classical molecular dynamics simulations, simulated HMS-Fe(IV)-O-HPA species, overview
malfunction
-
upon introduction of a steric barrier, which is suspected to obstruct the accommodation of the aromatic ring in the hydrophobic pocket during the final hydroxylation step, the racemization of product is obtained
malfunction
-
upon introduction of a steric barrier, which is suspected to obstruct the accommodation of the aromatic ring in the hydrophobic pocket during the final hydroxylation step, the racemization of product is obtained
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
HMAS_AMYOR
357
0
38339
Swiss-Prot
-
A0A5E4WJA1_9BURK
629
0
68919
TrEMBL
-
A0A5E4VXC5_9BURK
629
0
68974
TrEMBL
-
A0A2P7Z9R8_9ACTN
358
0
38633
TrEMBL
-
A0A445NHB2_STRNE
374
0
40065
TrEMBL
-
A0A5E4X1V6_9BURK
629
0
68944
TrEMBL
-
W9CUP1_9ACTN
355
0
38284
TrEMBL
-
A0A2H6APQ6_9BACT
145
0
16212
TrEMBL
-
A0A062WQG3_9ACTN
355
0
38284
TrEMBL
-
D6ES43_STRLI
358
0
38633
TrEMBL
-
A0A1V6E6V3_9BACT
136
0
14749
TrEMBL
-
A0A2P8AQ98_9ACTN
339
0
36787
TrEMBL
-
A0A1B9EJB1_9ACTN
343
0
37335
TrEMBL
-
A0A330KXG9_9PSED
348
0
38235
TrEMBL
-
A0A2P4UIU2_9ACTN
365
0
38607
TrEMBL
-
A0A1D8AVI2_9BACT
140
0
14991
TrEMBL
-
A0A0N0VKG3_9PSED
350
0
38388
TrEMBL
-
A0A5B7UMW8_9ACTN
371
0
39068
TrEMBL
-
A0A3E2YNL7_9ACTN
367
0
39219
TrEMBL
-
A0A5E4SFQ3_9BURK
629
0
68698
TrEMBL
-
A0A1J5T042_9ZZZZ
136
0
14758
TrEMBL
other Location (Reliability: 1 )
A0A075UYC1_9PSEU
350
0
37890
TrEMBL
-
A0A1V6DHG3_9BACT
143
0
15419
TrEMBL
-
A0A3N6GRC0_9ACTN
354
0
38554
TrEMBL
-
A0A5E4W8C5_9BURK
629
0
68988
TrEMBL
-
A0A2H6F7J6_9BACT
138
0
15723
TrEMBL
-
A0A2P4UIT4_9ACTN
354
0
37936
TrEMBL
-
A0A1L7F8E4_9PSEU
349
0
36739
TrEMBL
-
A0A2P8AWI8_9ACTN
368
0
39198
TrEMBL
-
A0A5B7V4T3_9ACTN
368
0
39701
TrEMBL
-
A0A0K2B0T1_STRA7
Streptomyces ambofaciens (strain ATCC 23877 / 3486 / DSM 40053 / JCM 4204 / NBRC 12836 / NRRL B-2516)
385
0
41683
TrEMBL
-
A0A3P5XBZ2_9BACL
139
0
15072
TrEMBL
-
A0A1D2I561_9ACTN
313
0
32403
TrEMBL
-
Q9Z4X7_STRCO
Streptomyces coelicolor (strain ATCC BAA-471 / A3(2) / M145)
371
0
40198
TrEMBL
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Streptomyces coelicolor (strain ATCC BAA-471 / A3(2) / M145)
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
40368
-
alpha,alpha, 2 * 40368, gel filtration, electrospray mass spectrometry
80000
-
gel filtration, electrospray mass spectrometry
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
dimer
-
alpha,alpha, 2 * 40368, gel filtration, electrospray mass spectrometry
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
crystal structure analysis
-
hanging drop method, the crystal structure of the hydroxymandelate synthase/Co2+/hydroxymandelate complex determined to a resolution of 2.3 A
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
I216N
-
site-directed mutagenesis, the mutant shows increased catalytic efficiency compared to the wild-type enzyme, the mutant produces 90% 4-hydroxmandelate and 10% 4-hydroxyphenylacetate from 4-hydroxyphenylpyruvate, which differs from the wild-type, that does not produce any 4-hydroxyphenylacetate
T214P
-
site-directed mutagenesis, mutant shows decreased catalytic efficiency compared to the wild-type enzyme
S201A
-
site-directed mutagenesis, the mutant enzyme produces 3% 4-hydroxyphenylacetate, and 97% 4-hydroxymandelate, the benzylic carbon retains predominant sp3 character in the TS for the initial hydrogen abstraction
S201A
-
site-directed mutagenesis, the mutant shows increased catalytic efficiency compared to the wild-type enzyme, the mutant produces 88% 4-hydroxmandelate and 12% 4-hydroxyphenylacetate from 4-hydroxyphenylpyruvate, which differs from the wild-type, that does not produce any 4-hydroxyphenylacetate
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
recombinant C-terminally strep-tagged enzyme from Escherichia coli strain BL21(DE3) by affinity chromatography
-
recombinant His-tagged protein, Ni-NTA resin
-
recombinant wild-type and mutant enzymes by ammonium sulfate fractionation, anion echange chromatography, and gel filtration
-
recombinant wild-type and mutant enzymes from Escherichia coli strain BL21(DE3) by ammonium sulfate fractionation, anion exchange chromatography, and gel filtration
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
expressed in Escherichia coli
-
expression of C-terminally strep-tagged enzyme in Escherichia coli strain BL21(DE3)
-
expression of wild-type and mutant enzymes in Escherichia coli strain BL21(DE3)
-
recombinant expression of wild-type and mutant enzymes
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Choroba, O.W.; Williams, D.H.; Spencer, J.B.
Biosynthesis of the vancomycin group of antibiotics: involvement of an unusual dioxygenase in the pathway to (S)-4-hydroxyphenylglycine
J. Am. Chem. Soc.
122
5389-5390
2000
Amycolatopsis orientalis
-
brenda
Brownlee, J.; He, P.; Moran, G.R.; Harrison, D.H.
Two roads diverged: the structure of hydroxymandelate synthase from Amycolatopsis orientalis in complex with 4-hydroxymandelate
Biochemistry
47
2002-2013
2008
Amycolatopsis orientalis
brenda
Conrad, J.A.; Moran, G.R.
The interaction of hydroxymandelate synthase with the 4-hydroxyphenylpyruvate dioxygenase inhibitor: NTBC
Inorg. Chim. Acta
361
1197-1201
2008
Amycolatopsis orientalis
brenda
Shah, D.D.; Conrad, J.A.; Heinz, B.; Brownlee, J.M.; Moran, G.R.
Evidence for the mechanism of hydroxylation by 4-hydroxyphenylpyruvate dioxygenase and hydroxymandelate synthase from intermediate partitioning in active site variants
Biochemistry
50
7694-7704
2011
Amycolatopsis orientalis
brenda
Wojcik, A.; Broclawik, E.; Siegbahn, P.E.; Borowski, T.
Mechanism of benzylic hydroxylation by 4-hydroxymandelate synthase. A computational study
Biochemistry
51
9570-9580
2012
Amycolatopsis orientalis
brenda
Shah, D.; Conrad, J.; Moran, G.
Intermediate partitioning kinetic isotope effects for the NIH shift of 4-hydroxyphenylpyruvate dioxygenase and the hydroxylation reaction of hydroxymandelate synthase reveal mechanistic complexity
Biochemistry
52
6097-6107
2013
Amycolatopsis orientalis
brenda
Di Giuro, C.M.; Konstantinovics, C.; Rinner, U.; Nowikow, C.; Leitner, E.; Straganz, G.D.
Chiral hydroxylation at the mononuclear nonheme Fe(II) center of 4-(S) hydroxymandelate synthase - a structure-activity relationship analysis
PLoS ONE
8
e68932
2013
Streptomyces coelicolor, Streptomyces coelicolor A3(2)
brenda
Select items on the left to see more content.
html completed
HOME
login
history
all enzymes
BRENDA home
History
1.13.11.46 4-hydroxymandelate synthase
more
top
Information
