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2a1x
From Proteopedia
| 2a1x, resolution 2.50Å () | |||||||||
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| Ligands: | , | ||||||||
| Gene: | PHYH, PAHX (Homo sapiens) | ||||||||
| Activity: | Phytanoyl-CoA dioxygenase, with EC number 1.14.11.18 | ||||||||
| Domains: | PhyH | ||||||||
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||
Human phytanoyl-coa 2-hydroxylase in complex with iron and 2-oxoglutarate
Refsum disease (RD), a neurological syndrome characterized by adult onset retinitis pigmentosa, anosmia, sensory neuropathy, and phytanic acidaemia, is caused by elevated levels of phytanic acid. Many cases of RD are associated with mutations in phytanoyl-CoA 2-hydroxylase (PAHX), an Fe(II) and 2-oxoglutarate (2OG)-dependent oxygenase that catalyzes the initial alpha-oxidation step in the degradation of phytenic acid in peroxisomes. We describe the x-ray crystallographic structure of PAHX to 2.5 A resolution complexed with Fe(II) and 2OG and predict the molecular consequences of mutations causing RD. Like other 2OG oxygenases, PAHX possesses a double-stranded beta-helix core, which supports three iron binding ligands (His(175), Asp(177), and His(264)); the 2-oxoacid group of 2OG binds to the Fe(II) in a bidentate manner. The manner in which PAHX binds to Fe(II) and 2OG together with the presence of a cysteine residue (Cys(191)) 6.7 A from the Fe(II) and two further histidine residues (His(155) and His(281)) at its active site distinguishes it from that of the other human 2OG oxygenase for which structures are available, factor inhibiting hypoxia-inducible factor. Of the 15 PAHX residues observed to be mutated in RD patients, 11 cluster in two distinct groups around the Fe(II) (Pro(173), His(175), Gln(176), Asp(177), and His(220)) and 2OG binding sites (Trp(193), Glu(197), Ile(199), Gly(204), Asn(269), and Arg(275)). PAHX may be the first of a new subfamily of coenzyme A-binding 2OG oxygenases.
Structure of human phytanoyl-CoA 2-hydroxylase identifies molecular mechanisms of Refsum disease., McDonough MA, Kavanagh KL, Butler D, Searls T, Oppermann U, Schofield CJ, J Biol Chem. 2005 Dec 9;280(49):41101-10. Epub 2005 Sep 25. PMID:16186124
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
About this Structure
2A1X is a 1 chain structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
- McDonough MA, Kavanagh KL, Butler D, Searls T, Oppermann U, Schofield CJ. Structure of human phytanoyl-CoA 2-hydroxylase identifies molecular mechanisms of Refsum disease. J Biol Chem. 2005 Dec 9;280(49):41101-10. Epub 2005 Sep 25. PMID:16186124 doi:10.1074/jbc.M507528200
Page seeded by OCA on Tue Feb 17 09:13:41 2009
Categories: Homo sapiens | Phytanoyl-CoA dioxygenase | Arrowsmith, C. | Bunkoczi, G. | Butler, D. | Delft, F Von. | Edwards, A. | Kavanagh, K L. | McDonough, M A. | Oppermann, U. | SGC, Structural Genomics Consortium. | Schofield, C J. | Searles, T. | Sundstrom, M. | Beta jelly roll | Double-stranded beta-helix | Sgc | Structural genomic | Structural genomics consortium
