6hlp
From Proteopedia
(Difference between revisions)
(New page: '''Unreleased structure''' The entry 6hlp is ON HOLD Authors: Schoppe, J., Ehrenmann, J., Klenk, C., Rucktooa, P., Schutz, M., Dore, A.S., Pluckthun, A. Description: Crystal structure ...) |
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of the Neurokinin 1 receptor in complex with the small molecule antagonist Netupitant== | |
| + | <StructureSection load='6hlp' size='340' side='right'caption='[[6hlp]], [[Resolution|resolution]] 2.20Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6hlp]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Pyrococcus_abyssi_GE5 Pyrococcus abyssi GE5]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6HLP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6HLP 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]] 2.2Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=GAW:2-[3,5-bis(trifluoromethyl)phenyl]-~{N},2-dimethyl-~{N}-[4-(2-methylphenyl)-6-(4-methylpiperazin-1-yl)pyridin-3-yl]propanamide'>GAW</scene>, <scene name='pdbligand=OLA:OLEIC+ACID'>OLA</scene>, <scene name='pdbligand=OLC:(2R)-2,3-DIHYDROXYPROPYL+(9Z)-OCTADEC-9-ENOATE'>OLC</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=YCM:S-(2-AMINO-2-OXOETHYL)-L-CYSTEINE'>YCM</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=6hlp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6hlp OCA], [https://pdbe.org/6hlp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6hlp RCSB], [https://www.ebi.ac.uk/pdbsum/6hlp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6hlp ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/Q9V2J8_PYRAB Q9V2J8_PYRAB] [https://www.uniprot.org/uniprot/NK1R_HUMAN NK1R_HUMAN] This is a receptor for the tachykinin neuropeptide substance P. It is probably associated with G proteins that activate a phosphatidylinositol-calcium second messenger system. The rank order of affinity of this receptor to tachykinins is: substance P > substance K > neuromedin-K. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Neurokinins (or tachykinins) are peptides that modulate a wide variety of human physiology through the neurokinin G protein-coupled receptor family, implicated in a diverse array of pathological processes. Here we report high-resolution crystal structures of the human NK1 receptor (NK1R) bound to two small-molecule antagonist therapeutics - aprepitant and netupitant and the progenitor antagonist CP-99,994. The structures reveal the detailed interactions between clinically approved antagonists and NK1R, which induce a distinct receptor conformation resulting in an interhelical hydrogen-bond network that cross-links the extracellular ends of helices V and VI. Furthermore, the high-resolution details of NK1R bound to netupitant establish a structural rationale for the lack of basal activity in NK1R. Taken together, these co-structures provide a comprehensive structural basis of NK1R antagonism and will facilitate the design of new therapeutics targeting the neurokinin receptor family. | ||
| - | + | Crystal structures of the human neurokinin 1 receptor in complex with clinically used antagonists.,Schoppe J, Ehrenmann J, Klenk C, Rucktooa P, Schutz M, Dore AS, Pluckthun A Nat Commun. 2019 Jan 3;10(1):17. doi: 10.1038/s41467-018-07939-8. PMID:30604743<ref>PMID:30604743</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: | + | <div class="pdbe-citations 6hlp" style="background-color:#fffaf0;"></div> |
| - | [[Category: | + | == References == |
| - | [[Category: | + | <references/> |
| - | [[Category: | + | __TOC__ |
| - | [[Category: | + | </StructureSection> |
| - | [[Category: | + | [[Category: Homo sapiens]] |
| - | [[Category: | + | [[Category: Large Structures]] |
| + | [[Category: Pyrococcus abyssi GE5]] | ||
| + | [[Category: Dore AS]] | ||
| + | [[Category: Ehrenmann J]] | ||
| + | [[Category: Klenk C]] | ||
| + | [[Category: Pluckthun A]] | ||
| + | [[Category: Rucktooa P]] | ||
| + | [[Category: Schoppe J]] | ||
| + | [[Category: Schutz M]] | ||
Current revision
Crystal structure of the Neurokinin 1 receptor in complex with the small molecule antagonist Netupitant
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