6hlp: Difference between revisions
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The | ==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. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6HLP FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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></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='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=6hlp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6hlp OCA], [http://pdbe.org/6hlp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6hlp RCSB], [http://www.ebi.ac.uk/pdbsum/6hlp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6hlp ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[[http://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> | ||
<div class="pdbe-citations 6hlp" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Dore, A S]] | |||
[[Category: Ehrenmann, J]] | |||
[[Category: Klenk, C]] | |||
[[Category: Pluckthun, A]] | [[Category: Pluckthun, A]] | ||
[[Category: Rucktooa, P]] | |||
[[Category: Schoppe, J]] | |||
[[Category: Schutz, M]] | [[Category: Schutz, M]] | ||
[[Category: | [[Category: 7-tm]] | ||
[[Category: | [[Category: Gpcr]] | ||
[[Category: | [[Category: Membrane protein]] | ||
[[Category: | [[Category: Signalling protein]] | ||
Revision as of 12:09, 16 January 2019
Crystal structure of the Neurokinin 1 receptor in complex with the small molecule antagonist Netupitant
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