2a1x
From Proteopedia
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|PDB= 2a1x |SIZE=350|CAPTION= <scene name='initialview01'>2a1x</scene>, resolution 2.50Å | |PDB= 2a1x |SIZE=350|CAPTION= <scene name='initialview01'>2a1x</scene>, resolution 2.50Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand= | + | |LIGAND= <scene name='pdbligand=AKG:2-OXYGLUTARIC+ACID'>AKG</scene>, <scene name='pdbligand=FE2:FE+(II)+ION'>FE2</scene> |
| - | |ACTIVITY= [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] | + | |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> |
|GENE= PHYH, PAHX ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= PHYH, PAHX ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | |DOMAIN= | ||
| + | |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> | ||
}} | }} | ||
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==Overview== | ==Overview== | ||
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. | 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. | ||
| - | |||
| - | ==Disease== | ||
| - | Known diseases associated with this structure: Refsum disease OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=602026 602026]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Searles, T.]] | [[Category: Searles, T.]] | ||
[[Category: Sundstrom, M.]] | [[Category: Sundstrom, M.]] | ||
| - | [[Category: AKG]] | ||
| - | [[Category: FE2]] | ||
[[Category: beta jelly roll]] | [[Category: beta jelly roll]] | ||
[[Category: double-stranded beta-helix]] | [[Category: double-stranded beta-helix]] | ||
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[[Category: structural genomics consortium]] | [[Category: structural genomics consortium]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 01:46:44 2008'' |
Revision as of 22:46, 30 March 2008
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| , resolution 2.50Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , | ||||||
| Gene: | PHYH, PAHX (Homo sapiens) | ||||||
| Activity: | Phytanoyl-CoA dioxygenase, with EC number 1.14.11.18 | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Human phytanoyl-coa 2-hydroxylase in complex with iron and 2-oxoglutarate
Overview
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 Structure
2A1X is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
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 Mon Mar 31 01:46:44 2008
Categories: Homo sapiens | Phytanoyl-CoA dioxygenase | Single protein | 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
