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Information on EC 1.14.16.4 - tryptophan 5-monooxygenase and Organism(s) Gallus gallus and UniProt Accession P70080

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IUBMB Comments
The active centre contains mononuclear iron(II). The enzyme is activated by phosphorylation, catalysed by a Ca2+-activated protein kinase. The 4a-hydroxytetrahydropteridine formed can dehydrate to 6,7-dihydropteridine, both spontaneously and by the action of EC 4.2.1.96, 4a-hydroxytetrahydrobiopterin dehydratase. The 6,7-dihydropteridine must be enzymically reduced back to tetrahydropteridine, by EC 1.5.1.34, 6,7-dihydropteridine reductase, before it slowly rearranges into the more stable but inactive compound 7,8-dihydropteridine.
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Gallus gallus
UNIPROT: P70080
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The taxonomic range for the selected organisms is: Gallus gallus
The enzyme appears in selected viruses and cellular organisms
Synonyms
tryptophan hydroxylase, tryptophan hydroxylase 2, tryptophan hydroxylase 1, tph-1, tryptophan hydroxylase-2, tryptophan hydroxylase-1, tph-2, tryptophan-5-hydroxylase, tryptophan 5-monooxygenase, tryptophan 5-hydroxylase, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
tryptophan hydroxylase
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tryptophan hydroxylase 1
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indoleacetic acid-5-hydroxylase
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-
-
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L-tryptophan hydroxylase
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-
-
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oxygenase, tryptophan 5-mono-
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-
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tryptophan 5-hydroxylase
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-
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tryptophan hydroxylase
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-
-
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tryptophan hydroxylase 2
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-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
redox reaction
-
-
-
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oxidation
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-
-
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reduction
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-
-
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PATHWAY SOURCE
PATHWAYS
-
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SYSTEMATIC NAME
IUBMB Comments
L-tryptophan,tetrahydrobiopterin:oxygen oxidoreductase (5-hydroxylating)
The active centre contains mononuclear iron(II). The enzyme is activated by phosphorylation, catalysed by a Ca2+-activated protein kinase. The 4a-hydroxytetrahydropteridine formed can dehydrate to 6,7-dihydropteridine, both spontaneously and by the action of EC 4.2.1.96, 4a-hydroxytetrahydrobiopterin dehydratase. The 6,7-dihydropteridine must be enzymically reduced back to tetrahydropteridine, by EC 1.5.1.34, 6,7-dihydropteridine reductase, before it slowly rearranges into the more stable but inactive compound 7,8-dihydropteridine.
CAS REGISTRY NUMBER
COMMENTARY hide
9037-21-2
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SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
L-tryptophan + (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
-
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
first and rate-determining step in the biosynthesis of the neurotransmitter serotonin
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-
?
L-tryptophan + (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
-
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
tetrahydrobiopterin
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Fe2+
the iron coordination is a distorted trigonal bipyramidal coordination with His273, His278, and Glu318 (partially bidentate) and one imidazole as ligands. The tryptophan stacks against Pro269 with a distance of 3.9 A between the iron and the tryptophan Czeta3 atom that is hydroxylated
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
L-tryptophan
substrate inhibition at concentrations above 0.015 mM
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0077
L-tryptophan
pH 7.0, 15°C, recombinant TPH1
0.039
O2
pH 7.0, 15°C, recombinant TPH1
0.324
tetrahydrobiopterin
pH 7.0, 15°C, recombinant TPH1
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
32
L-tryptophan
pH 7.0, 15°C, recombinant TPH1
22.8
O2
pH 7.0, 15°C, recombinant TPH1
43
tetrahydrobiopterin
pH 7.0, 15°C, recombinant TPH1
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.164
L-tryptophan
pH 7.0, 15°C, recombinant TPH1
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.6
purified recombinant TPH1
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
TPH1_CHICK
445
0
51139
Swiss-Prot
other Location (Reliability: 1)
PDB
SCOP
CATH
UNIPROT
ORGANISM
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
catalytic domain (DETLA1-100/DELTA415-445) of TPH1 in complex with the tryptophan substrate and an iron-bound imidazole, by vapor diffusion method with sitting drops, at 1.9 A resolution, crystallization time of 3-6 months. Loops of residues Leu124-Asp139 and Ile367-Thr369 close around the active site. The tryptophan substrate is bound close to the iron in a binding pocket distinct from the BH4 binding pocket. The hydrophobic part of the tryptophan binding pocket is lined by residues Tyr236, Thr266, Pro269, His273, Phe314, Phe319, and Ile367, while the polar interactions of the tryptophan are with Thr266, Ile367, and Ser337 and a salt bridge to Arg258. The overall structure is more compact with two loops closing around the active site, when compared to the structure of human catalytic domain of TPH1
purified enzyme without 7,8-dihydro-L-biopterin, sitting drop vapour diffusion method, 0.002 ml of 4.2 mg/ml protein in 20 mM Tris/NaOH, 100 mM (NH4)2SO4 pH 8.5, is mixed with 0.002 ml of reservoir solution containing 0.2 M imidazole malate, pH 8.5, 22.5% PEG 10000, and tetrahydrobiopterin in excess, X-ray diffraction structure determination and analysis at 3.0 A reslution
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
catalytic domain (DETLA1-100/DELTA415-445) of TPH1
recombinant catalytic domain of chicken TPH isoform 1 from Escherichia coli strain BL21(DE3) by anion exchange chromatography and gel filtration to homogeneity, release from the fusion by in vivo cleavage by a co-expressed ubiquitin-specific, carboxy-terminal protease
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
catalytic domain (DETLA1-100/DELTA415-445) of TPH1, expression in Escherichia coli
high yield expression of the catalytic domain of chicken TPH isoform 1, comprising residues 1-100 and 415-445, fused to ubiquitin in Escherichia coli strain BL21(DE3)
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Zhang, X.; Beaulieu, J.M.; Gainetdinov, R.R.; Caron, M.G.
Functional polymorphisms of the brain serotonin synthesizing enzyme tryptophan hydroxylase-2
Cell. Mol. Life Sci.
63
6-11
2006
Danio rerio, Gallus gallus, Drosophila melanogaster, Homo sapiens, Mus musculus, Rattus norvegicus
Manually annotated by BRENDA team
Nielsen, M.S.; Petersen, C.R.; Munch, A.; Vendelboe, T.V.; Boesen, J.; Harris, P.; Christensen, H.E.
A simple two step procedure for purification of the catalytic domain of chicken tryptophan hydroxylase 1 in a form suitable for crystallization
Protein Expr. Purif.
57
116-126
2008
Gallus gallus (P70080), Gallus gallus
Manually annotated by BRENDA team
Windahl, M.S.; Petersen, C.R.; Christensen, H.E.; Harris, P.
Crystal structure of tryptophan hydroxylase with bound amino acid substrate
Biochemistry
47
12087-12094
2008
Gallus gallus (P70080), Gallus gallus
Manually annotated by BRENDA team