View source for 2a1x


==Human phytanoyl-coa 2-hydroxylase in complex with iron and 2-oxoglutarate==
<StructureSection load='2a1x' size='340' side='right' caption='[[2a1x]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2a1x]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2A1X OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2A1X FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AKG:2-OXOGLUTARIC+ACID'>AKG</scene>, <scene name='pdbligand=FE2:FE+(II)+ION'>FE2</scene></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PHYH, PAHX ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Phytanoyl-CoA_dioxygenase Phytanoyl-CoA dioxygenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.11.18 1.14.11.18] </span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2a1x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2a1x OCA], [http://pdbe.org/2a1x PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2a1x RCSB], [http://www.ebi.ac.uk/pdbsum/2a1x PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2a1x ProSAT]</span></td></tr>
</table>
== Disease ==
[[http://www.uniprot.org/uniprot/PAHX_HUMAN PAHX_HUMAN]] Defects in PHYH are a cause of Refsum disease (RD) [MIM:[http://omim.org/entry/266500 266500]]. RD is an autosomal recessive disorder characterized clinically by a tetrad of abnormalities: retinitis pigmentosa, peripheral neuropathy, cerebellar ataxia, and elevated protein levels in the cerebrospinal fluid (CSF). Patients exhibit accumulation of the branched-chain fatty acid, phytanic acid, in blood and tissues. Less constant features are nerve deafness, anosmia, skeletal abnormalities, ichthyosis, cataracts and cardiac impairment. Manifestations of the disease appear in the second or third decade of life.<ref>PMID:9326939</ref> <ref>PMID:9326940</ref> <ref>PMID:10767344</ref> <ref>PMID:10709665</ref>  
== Function ==
[[http://www.uniprot.org/uniprot/PAHX_HUMAN PAHX_HUMAN]] Converts phytanoyl-CoA to 2-hydroxyphytanoyl-CoA. 
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/a1/2a1x_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2a1x ConSurf].
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== Publication Abstract from PubMed ==
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<ref>PMID:16186124</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Human]]
[[Category: Phytanoyl-CoA dioxygenase]]
[[Category: Arrowsmith, C]]
[[Category: Bunkoczi, G]]
[[Category: Butler, D]]
[[Category: Delft, F von]]
[[Category: Edwards, A]]
[[Category: Kavanagh, K L]]
[[Category: McDonough, M A]]
[[Category: Oppermann, U]]
[[Category: Structural genomic]]
[[Category: Schofield, C J]]
[[Category: Searles, T]]
[[Category: Sundstrom, M]]
[[Category: Beta jelly roll]]
[[Category: Double-stranded beta-helix]]
[[Category: Oxidoreductase]]
[[Category: Sgc]]