Phytanoyl-CoA dioxygenase

In enzymology, a phytanoyl-CoA dioxygenase (EC 1.14.11.18) is an enzyme that catalyzes the chemical reaction

phytanoyl-CoA + 2-oxoglutarate + O2 2-hydroxyphytanoyl-CoA + succinate + CO2
phytanoyl-CoA dioxygenase
The structure of human PAHX (PDB: 2A1X​). The Fe(II) cofactor is shown as an orange sphere, coordinated by two histidine and one aspartate residue (shown in green) and by the 2-oxoglutarate cosubstrate (shown in yellow).[1]
Identifiers
EC no.1.14.11.18
CAS no.185402-46-4
Databases
IntEnzIntEnz view
BRENDABRENDA entry
ExPASyNiceZyme view
KEGGKEGG entry
MetaCycmetabolic pathway
PRIAMprofile
PDB structuresRCSB PDB PDBe PDBsum
Gene OntologyAmiGO / QuickGO
Search
PMCarticles
PubMedarticles
NCBIproteins
phytanoyl-CoA 2-hydroxylase
Identifiers
SymbolPHYH
Alt. symbolsPAHX
NCBI gene5264
HGNC8940
OMIM602026
RefSeqNM_001037537
UniProtO14832
Other data
LocusChr. 10 p15.3-10p12.2
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StructuresSwiss-model
DomainsInterPro

The three substrates of this enzyme are phytanoyl-CoA, 2-oxoglutarate (2OG), and O2, whereas its three products are 2-hydroxyphytanoyl-CoA, succinate, and CO2.

This enzyme belongs to the family of iron(II)-dependent oxygenases, which typically incorporate one atom of dioxygen into the substrate and one atom into the succinate carboxylate group. The mechanism is complex, but is believed to involve ordered binding of 2-oxoglutarate to the iron(II) containing enzyme followed by substrate. Binding of substrate causes displacement of a water molecule from the iron(II) cofactor, leaving a vacant coordination position to which dioxygen binds. A rearrangement occurs to form a high energy iron-oxygen species (which is generally thought to be an iron(IV)=O species) that performs the actual oxidation reaction.[2][3]

Nomenclature

The systematic name of this enzyme class is phytanoyl-CoA, 2-oxoglutarate:oxygen oxidoreductase (2-hydroxylating). This enzyme is also called phytanoyl-CoA hydroxylase and phytanoyl-CoA alpha-hydroxylase.[4]

Examples

In humans, phytanoyl-CoA hydroxylase is encoded by the PHYH (aka PAHX) gene and is required for the alpha-oxidation of branched chain fatty acids (e.g. phytanic acid) in peroxisomes. PHYH deficiency results in the accumulation of large tissue stores of phytanic acid and is the major cause of Refsum disease.[5]

Iron(II) and 2OG-dependent oxygenases are common in microorganisms, plants, and animals; the human genome is predicted to contain about 80 examples, and the model plant Arabidopsis thaliana likely contains more.[2] In plants and microorganisms this enzyme family is associated with a large diversity of oxidative reactions.[6]

References
  1. McDonough MA, Kavanagh KL, Butler D, Searls T, Oppermann U, Schofield CJ (Dec 2005). "Structure of human phytanoyl-CoA 2-hydroxylase identifies molecular mechanisms of Refsum disease". The Journal of Biological Chemistry. 280 (49): 41101–10. doi:10.1074/jbc.M507528200. PMID 16186124.
  2. Hausinger, Robert P. (2015). "CHAPTER 1. Biochemical Diversity of 2-Oxoglutarate-Dependent Oxygenases". 2-Oxoglutarate-Dependent Oxygenases. Metallobiology. pp. 1–58. doi:10.1039/9781782621959-00001. ISBN 978-1-84973-950-4. S2CID 85596364.
  3. Martinez S, Hausinger RP (Aug 2015). "Catalytic Mechanisms of Fe(II)- and 2-Oxoglutarate-dependent Oxygenases". The Journal of Biological Chemistry. 290 (34): 20702–11. doi:10.1074/jbc.R115.648691. PMC 4543632. PMID 26152721.
  4. "PHYH phytanoyl-CoA 2-hydroxylase [ Homo sapiens (human) ]". National Center for Biotechnology Information.
  5. Mihalik SJ, Morrell JC, Kim D, Sacksteder KA, Watkins PA, Gould SJ (Oct 1997). "Identification of PAHX, a Refsum disease gene". Nature Genetics. 17 (2): 185–9. doi:10.1038/ng1097-185. PMID 9326939. S2CID 39214017.
  6. McDonough MA, Loenarz C, Chowdhury R, Clifton IJ, Schofield CJ (Dec 2010). "Structural studies on human 2-oxoglutarate dependent oxygenases". Current Opinion in Structural Biology. 20 (6): 659–72. doi:10.1016/j.sbi.2010.08.006. PMID 20888218.

Further reading
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