View source for 5k3i


==Crystal structure of Acyl-CoA oxidase-1 in Caenorhabditis elegans complexed with FAD and ATP==
<StructureSection load='5k3i' size='340' side='right'caption='[[5k3i]], [[Resolution|resolution]] 2.68&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5k3i]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Caenorhabditis_elegans Caenorhabditis elegans]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5K3I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5K3I FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.683&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5k3i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5k3i OCA], [https://pdbe.org/5k3i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5k3i RCSB], [https://www.ebi.ac.uk/pdbsum/5k3i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5k3i ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/ACX11_CAEEL ACX11_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).<ref>PMID:20610393</ref> <ref>PMID:25775534</ref> <ref>PMID:27551084</ref> <ref>PMID:29537254</ref> <ref>PMID:29863473</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Caenorhabditis 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<ref>PMID:27551084</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5k3i" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Caenorhabditis elegans]]
[[Category: Large Structures]]
[[Category: Bruner SD]]
[[Category: Butcher RA]]
[[Category: Jones RA]]
[[Category: Li K]]
[[Category: Zhang X]]