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PDBsum entry 5k3h
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Oxidoreductase
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PDB id
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5k3h
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References listed in PDB file
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Key reference
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Title
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Structural characterization of acyl-Coa oxidases reveals a direct link between pheromone biosynthesis and metabolic state in caenorhabditis elegans.
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Authors
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X.Zhang,
K.Li,
R.A.Jones,
S.D.Bruner,
R.A.Butcher.
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Ref.
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Proc Natl Acad Sci U S A, 2016,
113,
10055-10060.
[DOI no: ]
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PubMed id
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Abstract
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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.
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