Phytanoyl-CoA intro

Abstract | Introduction | Results | Discussion | Conclusion | Method | References

Biochemistry, genetics and bioinformatics are three of the quickest growing fields in modern research. They have quickly established themselves over the last decade as better computer techniques have been made available. This increase in the quality of instrumentation has lead to an explosion of new genomic data to analyse, the majority of which is available online for public access.

Our aim in this project is as follows;

we were given a target sequence -

>gi|134105315|pdb|2OPW|A Chain A, Crystal Structure Of Human Phytanoyl-Coa Dioxygenase Phyhd1 (Apo) MACLSPSQLQKFQQDGFLVLEGFLSAEECVAMQQRIGEIVAEMDVPLHCRTEFSTQEEEQLRAQGSTDYF LSSGDKIRFFFEKGVFDEKGNFLVPPEKSINKIGHALHAHDPVFKSITHSFKVQTLARSLGLQMPVVVQS MYIFKQPHFGGEVSPHQDASFLYTEPLGRVLGVWIAVEDATLENGCLWFIPGSHTSGVSRRMVRAPVGSA PGTSFLGSEPARDNSLFVPTPVQRGALVLIHGEVVHKSKQNLSDRSRQAYTFHLMEASGTTWSPENWLQP TAELPFPQLYT

using this our aim is to elucidate as much information about the potential protein as possible. We will be aiming to cover three main areas - Structure (Daniel), Sequence and Evolution (Eleanor) and Function (Liam). By covering all three of these areas we expect to gain oversight, hopefully, allowing us to deduce some of the properties of the protein, for example

binding sites
phloygeny trees
structural similarities
conservation of domains

Phytanoyl-CoA dioxygenase domain containing 1 isoform a

The structure of phytanoyl-CoA dioxygenase domain containing 1 isoform a (PHYHD) was determined using xray diffraction by Zhang et al. (2007) of the structural genomics consortium. Dioxygenases are oxidoreductases that oxidise a substrate by transferring both atoms of molecular oxygen. PHYHD is structurally similar to other members of the phytanoyl-CoA dioxygenase family of proteins, which function in the peroxisomal pathway of alpha-oxidation.

Peroxisomal alpha-oxidation

Phytanic acid is a long chain fatty acid constituent of the human diet. It is absorbed from a variety of foods, most notably the side chain of chlorophyll. The majority of long-chain fatty acids ingested in the diet are metabolised by beta-oxidation first in the peroxisome and then in the mitochondria. However, the methyl group on the third carbon of phytanic acid prevents beta-oxidation from occuring. Instead, the carboxyl group of phytanic acid is removed in alpha oxidation to allow for beta oxidation to take place.

Firstly, the phytanic acid undergoes the addition of co-enzyme A to the carboxyl group by long-chain fatty acid-CoA (LCFA-CoA) synthetase before being imported into the peroxisome. Once in the peroxisome the newly synthesised phytanoyl-CoA is metabolised by a phytanoyl-CoA dioxygenase to 2-hydroxyphytanoyl-CoA. Next, the alpha carbon is removed by 2-hydroxyphytanoyl-CoA lysase to form pristanal. Pristanal undergoes a further two reaction catalysed by pristanal dehydrogenase and LCFA-CoA synthase to form pristanoyl-CoA, a product able to enter the beta-oxidation pathway.

Refsum's disease

The result of defective alpha-oxidation is a build up of phytanic acid which manifests as Refsum's disease. Refsum's disease is charecterised by retin