View source for 5yhl


==Crystal structure of the human prostaglandin E receptor EP4 in complex with Fab and an antagonist Br-derivative==
<StructureSection load='5yhl' size='340' side='right'caption='[[5yhl]], [[Resolution|resolution]] 4.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5yhl]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5YHL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5YHL 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]] 4.2&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=8VL:4-[2-[[(2~{R})-2-(4-bromanylnaphthalen-1-yl)propanoyl]amino]-4-cyano-phenyl]butanoic+acid'>8VL</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=5yhl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5yhl OCA], [https://pdbe.org/5yhl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5yhl RCSB], [https://www.ebi.ac.uk/pdbsum/5yhl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5yhl ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/PE2R4_HUMAN PE2R4_HUMAN] Receptor for prostaglandin E2 (PGE2). The activity of this receptor is mediated by G(s) proteins that stimulate adenylate cyclase. Has a relaxing effect on smooth muscle. May play an important role in regulating renal hemodynamics, intestinal epithelial transport, adrenal aldosterone secretion, and uterine function.
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== Publication Abstract from PubMed ==
Prostaglandin E receptor EP4, a G-protein-coupled receptor, is involved in disorders such as cancer and autoimmune disease. Here, we report the crystal structure of human EP4 in complex with its antagonist ONO-AE3-208 and an inhibitory antibody at 3.2 A resolution. The structure reveals that the extracellular surface is occluded by the extracellular loops and that the antagonist lies at the interface with the lipid bilayer, proximal to the highly conserved Arg316 residue in the seventh transmembrane domain. Functional and docking studies demonstrate that the natural agonist PGE2 binds in a similar manner. This structural information also provides insight into the ligand entry pathway from the membrane bilayer to the EP4 binding pocket. Furthermore, the structure reveals that the antibody allosterically affects the ligand binding of EP4. These results should facilitate the design of new therapeutic drugs targeting both orthosteric and allosteric sites in this receptor family.

Ligand binding to human prostaglandin E receptor EP4 at the lipid-bilayer interface.,Toyoda Y, Morimoto K, Suno R, Horita S, Yamashita K, Hirata K, Sekiguchi Y, Yasuda S, Shiroishi M, Shimizu T, Urushibata Y, Kajiwara Y, Inazumi T, Hotta Y, Asada H, Nakane T, Shiimura Y, Nakagita T, Tsuge K, Yoshida S, Kuribara T, Hosoya T, Sugimoto Y, Nomura N, Sato M, Hirokawa T, Kinoshita M, Murata T, Takayama K, Yamamoto M, Narumiya S, Iwata S, Kobayashi T Nat Chem Biol. 2019 Jan;15(1):18-26. doi: 10.1038/s41589-018-0131-3. Epub 2018, Dec 3. PMID:30510193<ref>PMID:30510193</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 5yhl" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Horita S]]
[[Category: Iwata S]]
[[Category: Kobayashi T]]
[[Category: Morimoto K]]
[[Category: Suno R]]
[[Category: Toyoda Y]]