5k3g
Crystals structure of Acyl-CoA oxidase-1 in Caenorhabditis elegans, Apo form-I
Structural highlights
FunctionACX11_CAEEL Involved in the first step of peroxisomal beta-oxidation by catalyzing the desaturation of fatty acid-derived side chains (PubMed:25775534, PubMed:29537254, PubMed:27551084). Specifically, catalyzes the desaturation of fatty acids heptanoyl-CoA (C7), nonanoyl-CoA (C9), dodecanoyl-CoA (C12) and to a lesser extent pentanoyl-CoA (C5) and hexadecanoyl-CoA (C16), and hydroxylated fatty acid hydroxynonanoyl-CoA (PubMed:25775534, PubMed:29537254, PubMed:27551084). Also, catalyzes the desaturation fatty acid-derived side chains of ascaroside pheromones, which regulates development and behavior (PubMed:20610393, PubMed:25775534, PubMed:29537254, PubMed:29863473, PubMed:27551084). Specifically, shortens ascaroside with 5-carbon omega side chain (asc-omega-C5), 7-carbon side chain (asc-C7), 9-carbon side chain (asc-C9), 11-carbon side chain (asc-C11), 13-carbon side chain (asc-C13), 15-carbon side chain (asc-C15) and to a lesser extent ascarosides with 7-omega-carbon side chain (asc-omega-C7) (PubMed:25775534, PubMed:29537254, PubMed:27551084). Also shortens indol-3-carbonyl(IC)-ascarosides with 7-carbon side chain (IC-asc-C7) and to a lesser extent (IC)-ascarosides with 9-carbon side chain (IC-asc-C9) (PubMed:29863473). May associate and regulate the folding and/or the catalytic activity of other acyl-coenzyme A oxidases including acox-1.2, acox-1.3, acox-1.4 and acox-3 modulating the type of ascarosides produced (PubMed:25775534, PubMed:29537254, PubMed:29863473). In association with acox-1.3, catalyzes the desaturation of asc-C7-CoA but not of fatty acids or hydroxylated fatty acids (PubMed:25775534). Involved in the biosynthesis of asc-C6-MK (daumone 2) and asc-delta-C9 (daumone 3) but not asc-C7 (daumone 1); daumones are pheromones produced during unfavourable growth conditions which promote entry into the dauer stage (PubMed:20610393).[1] [2] [3] [4] [5] Publication Abstract from PubMedCaenorhabditis elegans secretes ascarosides as pheromones to communicate with other worms and to coordinate the development and behavior of the population. Peroxisomal beta-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 beta-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. Structural characterization of acyl-CoA oxidases reveals a direct link between pheromone biosynthesis and metabolic state in Caenorhabditis elegans.,Zhang X, Li K, Jones RA, Bruner SD, Butcher RA Proc Natl Acad Sci U S A. 2016 Sep 6;113(36):10055-60. doi:, 10.1073/pnas.1608262113. Epub 2016 Aug 22. PMID:27551084[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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