2a1x: Difference between revisions

Revision as of 18:30, 3 May 2008

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

OverviewOverview

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.

About this StructureAbout this Structure

2A1X is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

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 Page seeded by OCA on Sat May 3 18:30:00 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
 [[Image:2a1x.gif|left|200px]]
- {{Structure
+<!--
-|PDB= 2a1x |SIZE=350|CAPTION= <scene name='initialview01'>2a1x</scene>, resolution 2.50&Aring;
+The line below this paragraph, containing "STRUCTURE_2a1x", creates the "Structure Box" on the page.
-|SITE=
+You may change the PDB parameter (which sets the PDB file loaded into the applet)
-|LIGAND= <scene name='pdbligand=AKG:2-OXYGLUTARIC+ACID'>AKG</scene>, <scene name='pdbligand=FE2:FE+(II)+ION'>FE2</scene>
+or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-|ACTIVITY= <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>
+or leave the SCENE parameter empty for the default display.
-|GENE= PHYH, PAHX ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
+-->
-|DOMAIN=
+{{STRUCTURE_2a1x|  PDB=2a1x  |  SCENE=  }}
-|RELATEDENTRY=
-|RESOURCES=<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.ebi.ac.uk/pdbsum/2a1x PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2a1x RCSB]</span>
-}}
 '''Human phytanoyl-coa 2-hydroxylase in complex with iron and 2-oxoglutarate'''
@@ Line 38: / Line 35: @@
 [[Category: Searles, T.]]
 [[Category: Sundstrom, M.]]
-[[Category: beta jelly roll]]
+[[Category: Beta jelly roll]]
-[[Category: double-stranded beta-helix]]
+[[Category: Double-stranded beta-helix]]
-[[Category: sgc]]
+[[Category: Sgc]]
-[[Category: structural genomic]]
+[[Category: Structural genomic]]
-[[Category: structural genomics consortium]]
+[[Category: Structural genomics consortium]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 18:30:00 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 01:46:44 2008''