Abstracts now available online - Euro Fed Lipid

The structure of peroxisomal short length specific acyl-CoA oxidase
sheds light on the re-oxidation mechanism
Jenny Berglund, Lise Pedersen, Anette Henriksen
Carlsberg Laboratory, Biostructure group, Gamle Carlsberg vej 10, 2500 Valby
Peroxisomes are essential structures in all eukaryotic organisms. The organelles are
characterized by the presence of catalase, but also by the enzymatic activities needed
for β-oxidation of fatty acids. In β-oxidation cycles, which are the centers of fatty acid
breakdown, the lipid chain is shortened by a C
2
unit in each round. Where mammals
need both mitochondrial and peroxisomal β-oxidation cycles in order to oxidize all lipids,
plants are able to conduct the full process in the peroxisome. The acyl-CoA oxidase
family catalyzes the first and rate limiting step in the perixosomal β-oxidation cycle,
converting acyl-CoA to trans-2-enoyl-CoA. Arabidopsis thaliana express at least 4
different acyl-CoA oxidases, each with different chain length specificities.
The structure of the short length specific Arabidopsis acyl-CoA oxidase, ACX4, from
Arabidopsis thaliana has been determined in complex with the substrate analogue
acetoacetyl-CoA. It is the second structure of a plant acyl-CoA oxidase available, long
chain specific ACX1 was previously determined in our group. Where ACX1 is active as
a dimer, ACX4 instead forms an active tetramer in solution, thereby being structurally
much more similar to the related family of acyl-CoA dehydrogenases (ACAD). ACAD's
catalyze the equivalent oxidative reaction in mitochondria, but transfers the reducing
equivalent from FADH- to another flavoprotein, whereas ACX's are reoxidized by
molecular oxygen. The structure of ACX4 makes is possible to better understand the
mechanism of the oxygen reactivity in the oxidative half-reaction, substrate selectivity as
well as the catalysis of ACX.