2a1x

From Proteopedia

---

Revision as of 18:38, 12 November 2007

proteopedia linkproteopedia link

spinqualitylabelsall models 2a1x, resolution 2.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

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

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

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.

Disease

Known diseases associated with this structure: Refsum disease OMIM:[602026]

About this Structure

2A1X is a Single protein structure of sequence from Homo sapiens with FE2 and AKG as ligands. Active as Phytanoyl-CoA dioxygenase, with EC number 1.14.11.18 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 Nov 12 20:44:51 2007