6e59: Difference between revisions
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<StructureSection load='6e59' size='340' side='right'caption='[[6e59]], [[Resolution|resolution]] 3.40Å' scene=''> | <StructureSection load='6e59' size='340' side='right'caption='[[6e59]], [[Resolution|resolution]] 3.40Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6e59]] is a 1 chain structure with sequence from [ | <table><tr><td colspan='2'>[[6e59]] 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=6E59 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6E59 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=L76:1-(4-{[(2R,3S)-2-{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy}-3-(4-fluorophenyl)morpholin-4-yl]methyl}-1H-1,2,3-triazol-5-yl)-N,N-dimethylmethanamine'>L76</scene> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.4Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=L76:1-(4-{[(2R,3S)-2-{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy}-3-(4-fluorophenyl)morpholin-4-yl]methyl}-1H-1,2,3-triazol-5-yl)-N,N-dimethylmethanamine'>L76</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6e59 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6e59 OCA], [https://pdbe.org/6e59 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6e59 RCSB], [https://www.ebi.ac.uk/pdbsum/6e59 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6e59 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == 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;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Borek | [[Category: Pyrococcus abyssi GE5]] | ||
[[Category: Chapman | [[Category: Borek D]] | ||
[[Category: Clark | [[Category: Chapman K]] | ||
[[Category: Rosenbaum | [[Category: Clark L]] | ||
[[Category: Shao | [[Category: Rosenbaum DM]] | ||
[[Category: Wang | [[Category: Shao Z]] | ||
[[Category: Xu | [[Category: Wang J]] | ||
[[Category: Yin | [[Category: Xu Q]] | ||
[[Category: Yin J]] | |||
Latest revision as of 09:19, 11 October 2023
Crystal structure of the human NK1 tachykinin receptorCrystal structure of the human NK1 tachykinin receptor
Structural highlights
FunctionQ9V2J8_PYRAB 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. Publication Abstract from PubMedThe NK1 tachykinin G-protein-coupled receptor (GPCR) binds substance P, the first neuropeptide to be discovered in mammals. Through activation of NK1R, substance P modulates a wide variety of physiological and disease processes including nociception, inflammation, and depression. Human NK1R (hNK1R) modulators have shown promise in clinical trials for migraine, depression, and emesis. However, the only currently approved drugs targeting hNK1R are inhibitors for chemotherapy-induced nausea and vomiting (CINV). To better understand the molecular basis of ligand recognition and selectivity, we solved the crystal structure of hNK1R bound to the inhibitor L760735, a close analog of the drug aprepitant. Our crystal structure reveals the basis for antagonist interaction in the deep and narrow orthosteric pocket of the receptor. We used our structure as a template for computational docking and molecular-dynamics simulations to dissect the energetic importance of binding pocket interactions and model the binding of aprepitant. The structure of hNK1R is a valuable tool in the further development of tachykinin receptor modulators for multiple clinical applications. Crystal structure of the human NK1 tachykinin receptor.,Yin J, Chapman K, Clark LD, Shao Z, Borek D, Xu Q, Wang J, Rosenbaum DM Proc Natl Acad Sci U S A. 2018 Dec 11. pii: 1812717115. doi:, 10.1073/pnas.1812717115. PMID:30538204[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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