5K3I

Crystal structure of Acyl-CoA oxidase-1 in Caenorhabditis elegans complexed with FAD and ATP

Summary for 5K3I

• Entry DOI: 10.2210/pdb5k3i/pdb
• Related: 5K3G 5K3H 5K3J
• Descriptor: Acyl-coenzyme A oxidase, FLAVIN-ADENINE DINUCLEOTIDE, ADENOSINE-5'-TRIPHOSPHATE, ... (5 entities in total)
• Functional Keywords: dauer pheromone, ascarosides, b-oxidation, atp, oxidoreductase
• Biological source: Caenorhabditis elegans
• Total number of polymer chains: 8
• Total formula weight: 630534.85

Authors

Zhang, X.,Li, K.,Jones, R.A.,Bruner, S.D.,Butcher, R.A. (deposition date: 2016-05-19, release date: 2016-08-24, Last modification date: 2024-01-31)

Primary citation

Zhang, X.,Li, K.,Jones, R.A.,Bruner, S.D.,Butcher, R.A.
Structural characterization of acyl-CoA oxidases reveals a direct link between pheromone biosynthesis and metabolic state in Caenorhabditis elegans.
Proc.Natl.Acad.Sci.USA, 113:10055-10060, 2016

PubMed Abstract: Caenorhabditis elegans secretes ascarosides as pheromones to communicate with other worms and to coordinate the development and behavior of the population. Peroxisomal β-oxidation cycles shorten the side chains of ascaroside precursors to produce the short-chain ascaroside pheromones. Acyl-CoA oxidases, which catalyze the first step in these β-oxidation cycles, have different side chain-length specificities and enable C. elegans to regulate the production of specific ascaroside pheromones. Here, we determine the crystal structure of the acyl-CoA oxidase 1 (ACOX-1) homodimer and the ACOX-2 homodimer bound to its substrate. Our results provide a molecular basis for the substrate specificities of the acyl-CoA oxidases and reveal why some of these enzymes have a very broad substrate range, whereas others are quite specific. Our results also enable predictions to be made for the roles of uncharacterized acyl-CoA oxidases in C. elegans and in other nematode species. Remarkably, we show that most of the C. elegans acyl-CoA oxidases that participate in ascaroside biosynthesis contain a conserved ATP-binding pocket that lies at the dimer interface, and we identify key residues in this binding pocket. ATP binding induces a structural change that is associated with tighter binding of the FAD cofactor. Mutations that disrupt ATP binding reduce FAD binding and reduce enzyme activity. Thus, ATP may serve as a regulator of acyl-CoA oxidase activity, thereby directly linking ascaroside biosynthesis to ATP concentration and metabolic state.

PubMed: 27551084
DOI: 10.1073/pnas.1608262113

Experimental method

X-RAY DIFFRACTION (2.683 Å)