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| | ==Crystal structure of the human prostaglandin E receptor EP3 bound to prostaglandin E2== | | ==Crystal structure of the human prostaglandin E receptor EP3 bound to prostaglandin E2== |
| - | <StructureSection load='6ak3' size='340' side='right' caption='[[6ak3]], [[Resolution|resolution]] 2.90Å' scene=''> | + | <StructureSection load='6ak3' size='340' side='right'caption='[[6ak3]], [[Resolution|resolution]] 2.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6ak3]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_coli"_migula_1895 "bacillus coli" migula 1895]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6AK3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6AK3 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6ak3]] is a 2 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=6AK3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6AK3 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=P2E:(Z)-7-[(1R,2R,3R)-3-HYDROXY-2-[(E,3S)-3-HYDROXYOCT-1-ENYL]-5-OXO-CYCLOPENTYL]HEPT-5-ENOIC+ACID'>P2E</scene>, <scene name='pdbligand=POV:(2S)-3-(HEXADECANOYLOXY)-2-[(9Z)-OCTADEC-9-ENOYLOXY]PROPYL+2-(TRIMETHYLAMMONIO)ETHYL+PHOSPHATE'>POV</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.9Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">cybC ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 "Bacillus coli" Migula 1895])</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=P2E:(Z)-7-[(1R,2R,3R)-3-HYDROXY-2-[(E,3S)-3-HYDROXYOCT-1-ENYL]-5-OXO-CYCLOPENTYL]HEPT-5-ENOIC+ACID'>P2E</scene>, <scene name='pdbligand=POV:(2S)-3-(HEXADECANOYLOXY)-2-[(9Z)-OCTADEC-9-ENOYLOXY]PROPYL+2-(TRIMETHYLAMMONIO)ETHYL+PHOSPHATE'>POV</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6ak3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ak3 OCA], [http://pdbe.org/6ak3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ak3 RCSB], [http://www.ebi.ac.uk/pdbsum/6ak3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ak3 ProSAT]</span></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=6ak3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ak3 OCA], [https://pdbe.org/6ak3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ak3 RCSB], [https://www.ebi.ac.uk/pdbsum/6ak3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ak3 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/PE2R3_HUMAN PE2R3_HUMAN]] Receptor for prostaglandin E2 (PGE2) (PubMed:8307176, PubMed:7883006, PubMed:8117308, PubMed:8135729, PubMed:7981210). The activity of this receptor can couple to both the inhibition of adenylate cyclase mediated by G(i) proteins, and to an elevation of intracellular calcium (PubMed:7883006, PubMed:8117308, PubMed:8135729, PubMed:7981210). Required for normal development of fever in response to pyrinogens, including IL1B, prostaglandin E2 and bacterial lipopolysaccharide (LPS). Required for normal potentiation of platelet aggregation by prostaglandin E2, and thus plays a role in the regulation of blood coagulation. Required for increased HCO3(-) secretion in the duodenum in response to mucosal acidification, and thereby contributes to the protection of the mucosa against acid-induced ulceration. Not required for normal kidney function, normal urine volume and osmolality (By similarity).[UniProtKB:P30557]<ref>PMID:7883006</ref> <ref>PMID:7981210</ref> <ref>PMID:8117308</ref> <ref>PMID:8135729</ref> <ref>PMID:8307176</ref> | + | [https://www.uniprot.org/uniprot/C562_ECOLX C562_ECOLX] Electron-transport protein of unknown function.[https://www.uniprot.org/uniprot/PE2R3_HUMAN PE2R3_HUMAN] Receptor for prostaglandin E2 (PGE2) (PubMed:8307176, PubMed:7883006, PubMed:8117308, PubMed:8135729, PubMed:7981210). The activity of this receptor can couple to both the inhibition of adenylate cyclase mediated by G(i) proteins, and to an elevation of intracellular calcium (PubMed:7883006, PubMed:8117308, PubMed:8135729, PubMed:7981210). Required for normal development of fever in response to pyrinogens, including IL1B, prostaglandin E2 and bacterial lipopolysaccharide (LPS). Required for normal potentiation of platelet aggregation by prostaglandin E2, and thus plays a role in the regulation of blood coagulation. Required for increased HCO3(-) secretion in the duodenum in response to mucosal acidification, and thereby contributes to the protection of the mucosa against acid-induced ulceration. Not required for normal kidney function, normal urine volume and osmolality (By similarity).[UniProtKB:P30557]<ref>PMID:7883006</ref> <ref>PMID:7981210</ref> <ref>PMID:8117308</ref> <ref>PMID:8135729</ref> <ref>PMID:8307176</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Bacillus coli migula 1895]] | + | [[Category: Escherichia coli]] |
| - | [[Category: Iwata, S]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Kobayashi, T]] | + | [[Category: Large Structures]] |
| - | [[Category: Morimoto, K]] | + | [[Category: Iwata S]] |
| - | [[Category: Suno, R]] | + | [[Category: Kobayashi T]] |
| - | [[Category: Gpcr]] | + | [[Category: Morimoto K]] |
| - | [[Category: Lipid]] | + | [[Category: Suno R]] |
| - | [[Category: Membrane protein]]
| + | |
| - | [[Category: Prostanoid receptor]]
| + | |
| - | [[Category: Signaling protein]]
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| Structural highlights
Function
C562_ECOLX Electron-transport protein of unknown function.PE2R3_HUMAN Receptor for prostaglandin E2 (PGE2) (PubMed:8307176, PubMed:7883006, PubMed:8117308, PubMed:8135729, PubMed:7981210). The activity of this receptor can couple to both the inhibition of adenylate cyclase mediated by G(i) proteins, and to an elevation of intracellular calcium (PubMed:7883006, PubMed:8117308, PubMed:8135729, PubMed:7981210). Required for normal development of fever in response to pyrinogens, including IL1B, prostaglandin E2 and bacterial lipopolysaccharide (LPS). Required for normal potentiation of platelet aggregation by prostaglandin E2, and thus plays a role in the regulation of blood coagulation. Required for increased HCO3(-) secretion in the duodenum in response to mucosal acidification, and thereby contributes to the protection of the mucosa against acid-induced ulceration. Not required for normal kidney function, normal urine volume and osmolality (By similarity).[UniProtKB:P30557][1] [2] [3] [4] [5]
Publication Abstract from PubMed
Prostanoids are a series of bioactive lipid metabolites that function in an autacoid manner via activation of cognate G-protein-coupled receptors (GPCRs). Here, we report the crystal structure of human prostaglandin (PG) E receptor subtype EP3 bound to endogenous ligand PGE2 at 2.90 A resolution. The structure reveals important insights into the activation mechanism of prostanoid receptors and provides a molecular basis for the binding modes of endogenous ligands.
Crystal structure of the endogenous agonist-bound prostanoid receptor EP3.,Morimoto K, Suno R, Hotta Y, Yamashita K, Hirata K, Yamamoto M, Narumiya S, Iwata S, Kobayashi T Nat Chem Biol. 2019 Jan;15(1):8-10. doi: 10.1038/s41589-018-0171-8. Epub 2018 Dec, 3. PMID:30510192[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Schmid A, Thierauch KH, Schleuning WD, Dinter H. Splice variants of the human EP3 receptor for prostaglandin E2. Eur J Biochem. 1995 Feb 15;228(1):23-30. PMID:7883006
- ↑ An S, Yang J, So SW, Zeng L, Goetzl EJ. Isoforms of the EP3 subtype of human prostaglandin E2 receptor transduce both intracellular calcium and cAMP signals. Biochemistry. 1994 Dec 6;33(48):14496-502. PMID:7981210
- ↑ Yang J, Xia M, Goetzl EJ, An S. Cloning and expression of the EP3-subtype of human receptors for prostaglandin E2. Biochem Biophys Res Commun. 1994 Feb 15;198(3):999-1006. PMID:8117308
- ↑ Kunapuli SP, Fen Mao G, Bastepe M, Liu-Chen LY, Li S, Cheung PP, DeRiel JK, Ashby B. Cloning and expression of a prostaglandin E receptor EP3 subtype from human erythroleukaemia cells. Biochem J. 1994 Mar 1;298 ( Pt 2):263-7. PMID:8135729
- ↑ Adam M, Boie Y, Rushmore TH, Muller G, Bastien L, McKee KT, Metters KM, Abramovitz M. Cloning and expression of three isoforms of the human EP3 prostanoid receptor. FEBS Lett. 1994 Jan 31;338(2):170-4. PMID:8307176
- ↑ Morimoto K, Suno R, Hotta Y, Yamashita K, Hirata K, Yamamoto M, Narumiya S, Iwata S, Kobayashi T. Crystal structure of the endogenous agonist-bound prostanoid receptor EP3. Nat Chem Biol. 2019 Jan;15(1):8-10. doi: 10.1038/s41589-018-0171-8. Epub 2018 Dec, 3. PMID:30510192 doi:http://dx.doi.org/10.1038/s41589-018-0171-8
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