View source for 5yfi


==Crystal structure of the anti-human prostaglandin E receptor EP4 antibody Fab fragment==
<StructureSection load='5yfi' size='340' side='right'caption='[[5yfi]], [[Resolution|resolution]] 1.85&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5yfi]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5YFI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5YFI 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]] 1.848&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</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=5yfi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5yfi OCA], [https://pdbe.org/5yfi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5yfi RCSB], [https://www.ebi.ac.uk/pdbsum/5yfi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5yfi ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== 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>
</div>
<div class="pdbe-citations 5yfi" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Horita S]]
[[Category: Iwata S]]
[[Category: Kobayashi T]]
[[Category: Morimoto K]]
[[Category: Suno R]]
[[Category: Toyoda Y]]