6d26

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==Crystal structure of the prostaglandin D2 receptor CRTH2 with fevipiprant==
==Crystal structure of the prostaglandin D2 receptor CRTH2 with fevipiprant==
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<StructureSection load='6d26' size='340' side='right' caption='[[6d26]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
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<StructureSection load='6d26' size='340' side='right'caption='[[6d26]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[6d26]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6D26 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6D26 FirstGlance]. <br>
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<table><tr><td colspan='2'>[[6d26]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6D26 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6D26 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FSY:fevipiprant'>FSY</scene>, <scene name='pdbligand=OLA:OLEIC+ACID'>OLA</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene>, <scene name='pdbligand=PGO:S-1,2-PROPANEDIOL'>PGO</scene>, <scene name='pdbligand=SIN:SUCCINIC+ACID'>SIN</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FSY:fevipiprant'>FSY</scene>, <scene name='pdbligand=OLA:OLEIC+ACID'>OLA</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene>, <scene name='pdbligand=PGO:S-1,2-PROPANEDIOL'>PGO</scene>, <scene name='pdbligand=SIN:SUCCINIC+ACID'>SIN</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=YCM:S-(2-AMINO-2-OXOETHYL)-L-CYSTEINE'>YCM</scene></td></tr>
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=YCM:S-(2-AMINO-2-OXOETHYL)-L-CYSTEINE'>YCM</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6d27|6d27]]</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6d27|6d27]]</td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PTGDR2, CRTH2, DL1R, GPR44 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=6d26 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6d26 OCA], [http://pdbe.org/6d26 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6d26 RCSB], [http://www.ebi.ac.uk/pdbsum/6d26 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6d26 ProSAT]</span></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=6d26 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6d26 OCA], [http://pdbe.org/6d26 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6d26 RCSB], [http://www.ebi.ac.uk/pdbsum/6d26 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6d26 ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/PD2R2_HUMAN PD2R2_HUMAN]] Receptor for prostaglandin D2 (PGD2). Coupled to the G(i)-protein. Receptor activation may result in pertussis toxin-sensitive decreases in cAMP levels and Ca(2+) mobilization. PI3K signaling is also implicated in mediating PTGDR2 effects. PGD2 induced receptor internalization. CRTH2 internalization can be regulated by diverse kinases such as, PKC, PKA, GRK2, GPRK5/GRK5 and GRK6. Receptor activation is responsible, at least in part, in immune regulation and allergic/inflammation responses.<ref>PMID:11208866</ref> <ref>PMID:11535533</ref> <ref>PMID:17196174</ref>
[[http://www.uniprot.org/uniprot/PD2R2_HUMAN PD2R2_HUMAN]] Receptor for prostaglandin D2 (PGD2). Coupled to the G(i)-protein. Receptor activation may result in pertussis toxin-sensitive decreases in cAMP levels and Ca(2+) mobilization. PI3K signaling is also implicated in mediating PTGDR2 effects. PGD2 induced receptor internalization. CRTH2 internalization can be regulated by diverse kinases such as, PKC, PKA, GRK2, GPRK5/GRK5 and GRK6. Receptor activation is responsible, at least in part, in immune regulation and allergic/inflammation responses.<ref>PMID:11208866</ref> <ref>PMID:11535533</ref> <ref>PMID:17196174</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The signaling of prostaglandin D2 (PGD2) through G-protein-coupled receptor (GPCR) CRTH2 is a major pathway in type 2 inflammation. Compelling evidence suggests the therapeutic benefits of blocking CRTH2 signaling in many inflammatory disorders. Currently, a number of CRTH2 antagonists are under clinical investigation, and one compound, fevipiprant, has advanced to phase 3 clinical trials for asthma. Here, we present the crystal structures of human CRTH2 with two antagonists, fevipiprant and CAY10471. The structures, together with docking and ligand-binding data, reveal a semi-occluded pocket covered by a well-structured amino terminus and different binding modes of chemically diverse CRTH2 antagonists. Structural analysis suggests a ligand entry port and a binding process that is facilitated by opposite charge attraction for PGD2, which differs significantly from the binding pose and binding environment of lysophospholipids and endocannabinoids, revealing a new mechanism for lipid recognition by GPCRs.
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Structures of the Human PGD2 Receptor CRTH2 Reveal Novel Mechanisms for Ligand Recognition.,Wang L, Yao D, Deepak RNVK, Liu H, Xiao Q, Fan H, Gong W, Wei Z, Zhang C Mol Cell. 2018 Oct 4;72(1):48-59.e4. doi: 10.1016/j.molcel.2018.08.009. Epub 2018, Sep 13. PMID:30220562<ref>PMID:30220562</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 6d26" style="background-color:#fffaf0;"></div>
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Human]]
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[[Category: Large Structures]]
[[Category: Deepak, K]]
[[Category: Deepak, K]]
[[Category: Fan, H]]
[[Category: Fan, H]]

Revision as of 06:43, 17 April 2019

Crystal structure of the prostaglandin D2 receptor CRTH2 with fevipiprant

PDB ID 6d26

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