View source for 8ihk


==Cryo-EM structure of HCA3-Gi complex with acifran (local)==
<StructureSection load='8ihk' size='340' side='right'caption='[[8ihk]], [[Resolution|resolution]] 3.21&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8ihk]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8IHK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8IHK FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.21&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=P9X:(5~{S})-5-methyl-4-oxidanylidene-5-phenyl-furan-2-carboxylic+acid'>P9X</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=8ihk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8ihk OCA], [https://pdbe.org/8ihk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8ihk RCSB], [https://www.ebi.ac.uk/pdbsum/8ihk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8ihk ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/C562_ECOLX C562_ECOLX] Electron-transport protein of unknown function.[https://www.uniprot.org/uniprot/HCAR3_HUMAN HCAR3_HUMAN] Receptor for 3-OH-octanoid acid mediates a negative feedback regulation of adipocyte lipolysis to counteract prolipolytic influences under conditions of physiological or pathological increases in beta-oxidation rates. Acts as a low affinity receptor for nicotinic acid. This pharmacological effect requires nicotinic acid doses that are much higher than those provided by a normal diet.<ref>PMID:12522134</ref> <ref>PMID:19561068</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Hydroxycarboxylic acid receptors (HCA) are expressed in various tissues and immune cells. HCA2 and its agonist are thus important targets for treating inflammatory and metabolic disorders. Only limited information is available, however, on the active-state binding of HCAs with agonists. Here, we present cryo-EM structures of human HCA2-Gi and HCA3-Gi signaling complexes binding with multiple compounds bound. Agonists were revealed to form a salt bridge with arginine, which is conserved in the HCA family, to activate these receptors. Extracellular regions of the receptors form a lid-like structure that covers the ligand-binding pocket. Although transmembrane (TM) 6 in HCAs undergoes dynamic conformational changes, ligands do not directly interact with amino acids in TM6, suggesting that indirect signaling induces a slight shift in TM6 to activate Gi proteins. Structural analyses of agonist-bound HCA2 and HCA3 together with mutagenesis and molecular dynamics simulation provide molecular insights into HCA ligand recognition and activation mechanisms.

Structural basis of hydroxycarboxylic acid receptor signaling mechanisms through ligand binding.,Suzuki S, Tanaka K, Nishikawa K, Suzuki H, Oshima A, Fujiyoshi Y Nat Commun. 2023 Sep 22;14(1):5899. doi: 10.1038/s41467-023-41650-7. PMID:37736747<ref>PMID:37736747</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8ihk" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Escherichia coli]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Fujiyoshi Y]]
[[Category: Nishikawa K]]
[[Category: Suzuki H]]
[[Category: Suzuki S]]