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Literature summary for 1.14.11.18 extracted from

  • Mukherji, M.; Chien, W.; Kershaw, N.J.; Clifton, I.J.; Schofield, C.J.; Wierzbicki, A.S.; Lloyd, M.D.
    Structure-function analysis of phytanoyl-CoA 2-hydroxylase mutations causing Refsum's disease (2001), Hum. Mol. Genet., 10, 1971-1982.
    View publication on PubMed

Application

Application Comment Organism
diagnostics assays for Refsum‘s disease should not be based on PAHX activity alone. At least four different types of mutation cause loss of PAHX activity in vivo. Mutations to the peroxisomal targeting sequence do not affect catalytic function but probably affect targeting or degradation of the enzyme. A second group of mutations, including truncation and missense mutations, results in total loss of activity. A third group of mutations results in uncoupling of substrate oxidation from that of 2-oxoglutarate. A fourth group of mutations causes partial inactivation by hindering binding/utilization of the 2-oxoglutarate cosubstrate and/or iron(II) cofactor. From the therapeutic and biochemical view-point the latter two groups are particularly interesting since it may be possible to restore their activity with modified cosubstrates Homo sapiens

Cloned(Commentary)

Cloned (Comment) Organism
wild-type and mutant enzymes, expression in Escherichia coli Homo sapiens

Protein Variants

Protein Variants Comment Organism
D177A mutant enzyme does not catalyze hydroxylation of phytanoyl-CoA Homo sapiens
G204S mutation causes partial uncoupling of 2-oxoglutarate conversion from phytanoyl-CoA oxidation Homo sapiens
H175A mutant enzyme does not catalyze hydroxylation of phytanoyl-CoA Homo sapiens
N269H mutation causes partial uncoupling of 2-oxoglutarate conversion from phytanoyl-CoA oxidation Homo sapiens
P29S clinically observed mutant is fully active, mutation may result in a defective targeting of the protein to peroxisomes Homo sapiens
Q176K mutation causes partial uncoupling of 2-oxoglutarate conversion from phytanoyl-CoA oxidation Homo sapiens
R275Q mutation results in impaired 2-oxoglutarate binding Homo sapiens
R275W mutation results in impaired 2-oxoglutarate binding Homo sapiens

Localization

Localization Comment Organism GeneOntology No. Textmining
peroxisome
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Homo sapiens 5777
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Metals/Ions

Metals/Ions Comment Organism Structure
Iron required Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
phytanoyl-CoA + 2-oxoglutarate + O2 Homo sapiens 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 2-hydroxyphytanoyl-CoA + succinate + CO2
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Organism

Organism UniProt Comment Textmining
Homo sapiens O14832
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-

Purification (Commentary)

Purification (Comment) Organism
-
Homo sapiens

Source Tissue

Source Tissue Comment Organism Textmining
liver
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Homo sapiens
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Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
phytanoyl-CoA + 2-oxoglutarate + O2 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 Homo sapiens 2-hydroxyphytanoyl-CoA + succinate + CO2
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