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2a1x

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Revision as of 06:36, 31 January 2018

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

Structural highlights

2a1x is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Gene:	PHYH, PAHX (HUMAN)
Activity:	Phytanoyl-CoA dioxygenase, with EC number 1.14.11.18
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.

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^[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ 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
↑ 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
↑ 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
↑ 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
↑ 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

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2a1x"

@@ Line 1: / Line 1: @@
 ==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=''>
@@ Line 6: / Line 7: @@
 <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]</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 ==
@@ Line 16: / Line 17: @@
 Check<jmol>
   <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>
     <text>to colour the structure by Evolutionary Conservation</text>
@@ Line 40: / Line 41: @@
 [[Category: Bunkoczi, G]]
 [[Category: Butler, D]]
-[[Category: Delft, F Von]]
+[[Category: Delft, F von]]
 [[Category: Edwards, A]]
 [[Category: Kavanagh, K L]]

2a1x

From Proteopedia

Revision as of 06:36, 31 January 2018

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

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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