Information on EC 1.14.11.18 - phytanoyl-CoA dioxygenase and Organism(s) Homo sapiens

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The taxonomic range for the selected organisms is: Homo sapiens

The enzyme appears in selected viruses and cellular organisms

EC NUMBER
COMMENTARY hide
1.14.11.18
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RECOMMENDED NAME
GeneOntology No.
phytanoyl-CoA dioxygenase
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
oxidation
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redox reaction
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reduction
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SYSTEMATIC NAME
IUBMB Comments
phytanoyl-CoA, 2-oxoglutarate:oxygen oxidoreductase (2-hydroxylating)
Part of the peroxisomal phytanic acid alpha-oxidation pathway. Requires Fe2+ and ascorbate.
CAS REGISTRY NUMBER
COMMENTARY hide
185402-46-4
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ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
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infantile-onset Adult Refsum's disease due to phytanoyl-CoA hydroxylase ((PHYH) c.164delT, p.L55fsX12) mutation. The challenges of a successful pregnancy in a patient with Adult Refsums disease due to phytanoyl-CoA hydroxylase deficiency
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
3,7-dimethyloctan-6-enoyl-CoA + 2-oxoglutarate + O2
3,7-dimethyl-2-hydroxyocta-7-enoyl-CoA + succinate + CO2
show the reaction diagram
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75.2 of the activity with 3-methylhexadecanoyl-CoA
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?
3-ethylnonanoyl-CoA + 2-oxoglutarate + O2
3-ethoxy-2-hydroxyhexadecanoyl-CoA + succinate + CO2
show the reaction diagram
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64.7% of the activity with 3-methylhexadecanoyl-CoA
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?
3-methyl-5-phenyl-pentanoyl-CoA + 2-oxoglutarate + O2
2-hydroxy-3-methyl-5-phenylpentanoyl-CoA + succinate + CO2
show the reaction diagram
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53% of the activity with 3-methylhexadecanoyl-CoA
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?
3-methyldodecanoyl-CoA + 2-oxoglutarate + O2
2-hydroxy-3-methyldodecanoyl-CoA + succinate + CO2
show the reaction diagram
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110% of the activity with 3-methylhexadecanoyl-CoA
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?
3-methylheptanoyl-CoA + 2-oxoglutarate + O2
2-hydroxy-3-methylheptanoyl-CoA + succinate + CO2
show the reaction diagram
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16.2% of the activity with 3-methylhexadecanoyl-CoA
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?
3-methylhexadecanoyl-CoA + 2-oxoglutarate + O2
2-hydroxy-3-methylhexadecanoyl-CoA + succinate + CO2
show the reaction diagram
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?
3-methylnonanoyl-CoA + 2-oxoglutarate + O2
2-hydroxy-3-methylnonanoyl-CoA + succinate + CO2
show the reaction diagram
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111% of the activity with 3-methylhexadecanoyl-CoA
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?
3-methylundecanoyl-CoA + 2-oxoglutarate + O2
2-hydroxy-3-methylundecanoyl-CoA + succinate + CO2
show the reaction diagram
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110% of the activity with 3-methylhexadecanoyl-CoA
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?
butanoyl-CoA + 2-oxoglutarate + O2
2-hydroxybutanoyl-CoA + succinate + CO2
show the reaction diagram
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?
decanoyl-CoA + 2-oxoglutarate + O2
2-hydroxydecanoyl-CoA + succinate + CO2
show the reaction diagram
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-
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?
dodecanoyl-CoA + 2-oxoglutarate + O2
2-hydroxydodecanoyl-CoA + succinate + CO2
show the reaction diagram
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-
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?
hexadecanoyl-CoA + 2-oxoglutarate + O2
2-hydroxyhexadecanoyl-CoA + succinate + CO2
show the reaction diagram
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?
hexanoyl-CoA + 2-oxoglutarate + O2
2-hydroxyhexanoyl-CoA + succinate + CO2
show the reaction diagram
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?
isovaleryl-CoA + 2-oxoglutarate + O2
?
show the reaction diagram
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?
octadecanoyl-CoA + 2-oxoglutarate + O2
2-hydroxyoctadecanoyl-CoA + succinate + CO2
show the reaction diagram
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?
octanoyl-CoA + 2-oxoglutarate + O2
2-hydroxyoctanoyl-CoA + succinate + CO2
show the reaction diagram
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?
phytanoyl-CoA + 2-oxoglutarate
2-hydroxyphytanoyl-CoA + succinate + CO2
show the reaction diagram
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ir
phytanoyl-CoA + 2-oxoglutarate + O2
2-hydroxyphytanoyl-CoA + succinate + CO2
show the reaction diagram
phytanoyl-CoA + 2-oxoglutarate + O2
alpha-hydroxyphytanoyl-CoA + succinate + CO2
show the reaction diagram
tetradecanoyl-CoA + 2-oxoglutarate + O2
2-hydroxytetradecanoyl-CoA + succinate + CO2
show the reaction diagram
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?
additional information
?
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NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
phytanoyl-CoA + 2-oxoglutarate + O2
2-hydroxyphytanoyl-CoA + succinate + CO2
show the reaction diagram
O14832
Refsum‘s disease ia a neurological syndrome characterized by adult-onset retinitis pigmentosa, anosemia, sensory neuropathy and phytanic acidaemia. Many cases are caused by mutations in peroxidomal oxygenase phytanoyl-CoA 2-hydroxylase
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?
additional information
?
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
additional information
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UTP, CTP, ITP, AMP, ADP, NAD+ and FAD can not act as cofactors, ATP and GTP can be replaced by adenosine-5'-O-(3-thiotriphosphate), adenylylimidodiphosphate, adenylyl-(beta,gamma-methylene)-diphosphonate and guanylyl-imidodiphosphate
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
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Cu2+, Mn2+ or Zn2+ can not replace Fe2+
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
2-methylhexadecanoyl-CoA
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56% of control activity
ATP
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at 0.1 mM Fe2+ 4 mM ATP inhibits enzyme activity. At increased Fe2+ concentrations ATP stimulates with a maximum at 64 mM ATP for 1.0 mM Fe2+
GTP
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at 0.1 mM Fe2+ 4 mM ATP inhibits enzyme activity. At increased Fe2+ concentrations ATP stimulates with a maximum at 64 mM ATP for 1.0 mM Fe2+
hexadecanoyl-CoA
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74% of control activity
propyl gallate
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no activity with 1 mM, interacts with iron binding
additional information
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not inhibited by bifonazole, clotrimazole, miconazole, ketoconazole
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
2-hydroxyphytanoyl-CoA
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albumin
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0.05 mM 3-methylhexadecanoyl-CoA, no hydroxylation in absence of albumin. Hydroxylation of 3-methylnonanoyl-CoA or 3-methyldodecanoyl-CoA is much less dependent on the presence of albumin
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ascorbate
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2.5fold induction at 5 mM
ATP
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at 0.1 mM Fe2+ 4 mM ATP inhibits enzyme activity. At increased Fe2+ concentrations ATP stimulates with a maximum at 64 mM ATP for 1.0 mM Fe2+
GTP
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at 0.1 mM Fe2+ 4 mM GTP inhibits enzyme activity. At increased Fe2+ concentrations ATP stimulates with a maximum at 64 mM GTP for 1.0 mM Fe2+
imidazole
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at 0.1 mM Fe2+ 4 mM ATP inhibits enzyme activity. At increased Fe2+ concentrations ATP stimulates with a maximum at 64 mM ATP for 1.0 mM Fe2+; stimulates at 1.0 mM Fe2+
SCP-2
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phytanoylis efficiently 2-hydroxylated by PAHX in vitro in the presence of mature SCO-2. SCP-2 increases discrimination between straight-chain and branched-chain substrates, i.e. it decreases activity with straight chain substrates and increase activity with branched-chain substrates. In vivo substrates for PAHX may be SCP-2 complexes
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.049
2-oxoglutarate
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0.0408
3-methylhexadecanoyl-CoA
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.000002
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in kidney cell line 293, activity can be induced 4fold by phytanic acid
0.0000022
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in fibroblast homogenate
0.0000031
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in hepatoma cell line HepG2, no induction by phytanic acid
0.000041
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in liver homogenate
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6.5 - 8.5
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at pH 6.5 over 80%, at pH 8.5 50% of control activity
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
PDB
SCOP
CATH
ORGANISM
UNIPROT
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
35400
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mature protein after cleavage of presumed leader sequence, calculation from cDNA sequence
35440
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calculated from amino acid sequence without N-terminal methionine
41200
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precursor protein with peroxisomal targeting signal type 2, calculation from cDNA sequence
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
proteolytic modification
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unprocessed proenzyme contains a N-terminal peroxisomal targeting sequence that is cleaved to give mature PAHX. Both forms are able to hydroxylate a range of CoA derivatives, but under the same assay conditions, the N-terminal Hexa-His-tagged unprocessed form is less active than the nontagged mature form
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
hanging drop vapour diffusion method in 21% polyethylene glycol 3350, 0.3 M triammonium citrate, pH 7.1, at 18°C
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Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
carboxymethyl-Sepharose cation exchange chromatography and Superdex S75 gel filtration
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Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expressed in Escherichia coli
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in bacterial expression vector pMALc2
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in bacterial expression vector pQE-31
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in mammalian expression vector pcDNA3
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in yeast expression vector
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wild-type and mutant enzymes, expression in Escherichia coli
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
E197Q
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disruption of the 2-oxoglutarate binding pocket
F275S
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places a polar side chain in a hydrophobic pocket and possibly interferes with the overall structure or impair protein folding
H213A
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insoluble mutant enzyme
H259A
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mutation removes two of the hydrogen bonds and probably destabilizes the beta-turn, which in turn destabilizes the core double stranded beta-helix
H264A
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activity with phytanoyl-CoA is 7.5 of the wild-type activity
I199F
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disruption of the 2-oxoglutarate binding pocket
N83Y
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disruption of protein-protein interactions proposed to involve PAHX, such as that with sterol carrier protein-2, proposed to be responsible for solubilization and presentation of phytanoyl-CoA to PAHX
P29S
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clinically observed mutant is fully active, mutation may result in a defective targeting of the protein to peroxisomes
Q176A
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activity with phytanoyl-CoA is 16.3% of the wild-type activity
Q176K
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mutation causes partial uncoupling of 2-oxoglutarate conversion from phytanoyl-CoA oxidation
R245Q
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disruption of protein-protein interactions proposed to involve PAHX, such as that with sterol carrier protein-2, proposed to be responsible for solubilization and presentation of phytanoyl-CoA to PAHX
W193R
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disruption of the 2-oxoglutarate binding pocket
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
diagnostics
medicine
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treatment of Refsum disease