2a1x: Difference between revisions

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==Human phytanoyl-coa 2-hydroxylase in complex with iron and 2-oxoglutarate==
==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=''>
<StructureSection load='2a1x' size='340' side='right'caption='[[2a1x]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[2a1x]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. 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>
<table><tr><td colspan='2'>[[2a1x]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. 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 [https://proteopedia.org/fgij/fg.htm?mol=2A1X FirstGlance]. <br>
</td></tr><tr><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><br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5&#8491;</td></tr>
<tr><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 Homo sapiens])</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AKG:2-OXOGLUTARIC+ACID'>AKG</scene>, <scene name='pdbligand=FE2:FE+(II)+ION'>FE2</scene></td></tr>
<tr><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'>[https://proteopedia.org/fgij/fg.htm?mol=2a1x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2a1x OCA], [https://pdbe.org/2a1x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2a1x RCSB], [https://www.ebi.ac.uk/pdbsum/2a1x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2a1x ProSAT]</span></td></tr>
<tr><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://www.rcsb.org/pdb/explore.do?structureId=2a1x RCSB], [http://www.ebi.ac.uk/pdbsum/2a1x PDBsum]</span></td></tr>
</table>
<table>
== Disease ==
== 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>
[https://www.uniprot.org/uniprot/PAHX_HUMAN PAHX_HUMAN] Defects in PHYH are a cause of Refsum disease (RD) [MIM:[https://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 ==
== Function ==
[[http://www.uniprot.org/uniprot/PAHX_HUMAN PAHX_HUMAN]] Converts phytanoyl-CoA to 2-hydroxyphytanoyl-CoA.  
[https://www.uniprot.org/uniprot/PAHX_HUMAN PAHX_HUMAN] Converts phytanoyl-CoA to 2-hydroxyphytanoyl-CoA.
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
Check<jmol>
   <jmolCheckbox>
   <jmolCheckbox>
     <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/a1/2a1x_consurf.spt"</scriptWhenChecked>
     <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>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>
   </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/chain_selection.php?pdb_ID=2ata ConSurf].
</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].
<div style="clear:both"></div>
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== 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>
==See Also==
</div>
*[[Dioxygenase 3D structures|Dioxygenase 3D structures]]
== References ==
== References ==
<references/>
<references/>
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</StructureSection>
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Phytanoyl-CoA dioxygenase]]
[[Category: Large Structures]]
[[Category: Arrowsmith, C.]]
[[Category: Arrowsmith C]]
[[Category: Bunkoczi, G.]]
[[Category: Bunkoczi G]]
[[Category: Butler, D.]]
[[Category: Butler D]]
[[Category: Delft, F Von.]]
[[Category: Edwards A]]
[[Category: Edwards, A.]]
[[Category: Kavanagh KL]]
[[Category: Kavanagh, K L.]]
[[Category: McDonough MA]]
[[Category: McDonough, M A.]]
[[Category: Oppermann U]]
[[Category: Oppermann, U.]]
[[Category: Schofield CJ]]
[[Category: SGC, Structural Genomics Consortium.]]
[[Category: Searles T]]
[[Category: Schofield, C J.]]
[[Category: Sundstrom M]]
[[Category: Searles, T.]]
[[Category: Von Delft F]]
[[Category: Sundstrom, M.]]
[[Category: Beta jelly roll]]
[[Category: Double-stranded beta-helix]]
[[Category: Oxidoreductase]]
[[Category: Sgc]]
[[Category: Structural genomic]]
[[Category: Structural genomics consortium]]

Latest revision as of 12:10, 14 February 2024

Human phytanoyl-coa 2-hydroxylase in complex with iron and 2-oxoglutarateHuman phytanoyl-coa 2-hydroxylase in complex with iron and 2-oxoglutarate

Structural highlights

2a1x is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.5Å
Ligands:,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

PAHX_HUMAN Defects in PHYH are a cause of Refsum disease (RD) [MIM: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.[1] [2] [3] [4]

Function

PAHX_HUMAN Converts phytanoyl-CoA to 2-hydroxyphytanoyl-CoA.

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

See Also

References

  1. ↑ Mihalik SJ, Morrell JC, Kim D, Sacksteder KA, Watkins PA, Gould SJ. Identification of PAHX, a Refsum disease gene. Nat Genet. 1997 Oct;17(2):185-9. PMID:9326939 doi:10.1038/ng1097-185
  2. ↑ Jansen GA, Ofman R, Ferdinandusse S, Ijlst L, Muijsers AO, Skjeldal OH, Stokke O, Jakobs C, Besley GT, Wraith JE, Wanders RJ. Refsum disease is caused by mutations in the phytanoyl-CoA hydroxylase gene. Nat Genet. 1997 Oct;17(2):190-3. PMID:9326940 doi:10.1038/ng1097-190
  3. ↑ Jansen GA, Hogenhout EM, Ferdinandusse S, Waterham HR, Ofman R, Jakobs C, Skjeldal OH, Wanders RJ. Human phytanoyl-CoA hydroxylase: resolution of the gene structure and the molecular basis of Refsum's disease. Hum Mol Genet. 2000 May 1;9(8):1195-200. PMID:10767344
  4. ↑ Jansen GA, Ferdinandusse S, Hogenhout EM, Verhoeven NM, Jakobs C, Wanders RJ. Phytanoyl-CoA hydroxylase deficiency. Enzymological and molecular basis of classical Refsum disease. Adv Exp Med Biol. 1999;466:371-6. PMID:10709665

2a1x, resolution 2.50Å

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