View source for 6hll


==Crystal structure of the Neurokinin 1 receptor in complex with the small molecule antagonist CP-99,994==
<StructureSection load='6hll' size='340' side='right'caption='[[6hll]], [[Resolution|resolution]] 3.27&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6hll]] 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=6HLL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6HLL 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]] 3.27&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GBK:(2~{S},3~{S})-~{N}-[(2-methoxyphenyl)methyl]-2-phenyl-piperidin-3-amine'>GBK</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=6hll FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6hll OCA], [https://pdbe.org/6hll PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6hll RCSB], [https://www.ebi.ac.uk/pdbsum/6hll PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6hll 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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6hll" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[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]]