9vu0: Difference between revisions
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==Structure of hTRPV1 in apo state== | |||
<StructureSection load='9vu0' size='340' side='right'caption='[[9vu0]], [[Resolution|resolution]] 2.63Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[9vu0]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9VU0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9VU0 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.63Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=POV:(2S)-3-(HEXADECANOYLOXY)-2-[(9Z)-OCTADEC-9-ENOYLOXY]PROPYL+2-(TRIMETHYLAMMONIO)ETHYL+PHOSPHATE'>POV</scene>, <scene name='pdbligand=YBG:[(2~{S})-1-hexadecanoyloxy-3-[oxidanyl-[(2~{R},3~{S},5~{R},6~{R})-2,3,4,5,6-pentakis(oxidanyl)cyclohexyl]oxy-phosphoryl]oxy-propan-2-yl]+(~{E})-octadec-9-enoate'>YBG</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=9vu0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9vu0 OCA], [https://pdbe.org/9vu0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9vu0 RCSB], [https://www.ebi.ac.uk/pdbsum/9vu0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9vu0 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/TRPV1_HUMAN TRPV1_HUMAN] Ligand-activated non-selective calcium permeant cation channel involved in detection of noxious chemical and thermal stimuli. Seems to mediate proton influx and may be involved in intracellular acidosis in nociceptive neurons. Involved in mediation of inflammatory pain and hyperalgesia. Sensitized by a phosphatidylinositol second messenger system activated by receptor tyrosine kinases, which involves PKC isozymes and PCL. Activation by vanilloids, like capsaicin, and temperatures higher than 42 degrees Celsius, exhibits a time- and Ca(2+)-dependent outward rectification, followed by a long-lasting refractory state. Mild extracellular acidic pH (6.5) potentiates channel activation by noxious heat and vanilloids, whereas acidic conditions (pH <6) directly activate the channel. Can be activated by endogenous compounds, including 12-hydroperoxytetraenoic acid and bradykinin. Acts as ionotropic endocannabinoid receptor with central neuromodulatory effects. Triggers a form of long-term depression (TRPV1-LTD) mediated by the endocannabinoid anandamine in the hippocampus and nucleus accumbens by affecting AMPA receptors endocytosis.[UniProtKB:O35433]<ref>PMID:11050376</ref> <ref>PMID:11226139</ref> <ref>PMID:11243859</ref> <ref>PMID:12077606</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
BACKGROUND: Transient receptor potential vanilloid 1 (TRPV1) and ankyrin 1 (TRPA1) are two nociceptive TRP channel subtypes that play central roles in cough hypersensitivity. PURPOSE: This study evaluated the antitussive efficacy of liquiritin apioside (LIQA) and liquiritin (LIQ), two major flavonoid glycosides from licorice, in acute chemically induced cough models, and investigated their modulations of TRPA1 and TRPV1. METHODS: In guinea pig models, cough was induced by capsaicin (a TRPV1 agonist) and cinnamaldehyde (a TRPA1 agonist), respectively. The inhibitory effects of LIQA and LIQ against TRPA1 and TRPV1 were assessed using electrophysiological profiling and fluorescence-based calcium assays. To elucidate the underlying mechanisms, high-resolution cryo-electron microscopy (cryo-EM) structural analysis, and molecular simulations were conducted. RESULTS: LIQA and LIQ significantly reduced cough frequency in the guinea pig models. Electrophysiological profiling revealed that LIQA suppressed human TRPA1 (hTRPA1) channel activity, while LIQ blocked human TRPV1 (hTRPV1) activation. High-resolution cryo-EM structures of hTRPA1/LIQA (2.59 A) and hTRPV1/LIQ (3.05 A) complexes were obtained. Structural analysis indicates that LIQA stabilizes hTRPA1 in a closed conformation with T624 at the coupling region site, whereas LIQ interacts with S512 through hydrogen bonding in the deep S4-S5 site of hTRPV1, thereby inhibiting pore opening. CONCLUSION: This study establishes LIQA and LIQ as lead compounds with acute antitussive activities mediated by TRPA1/TRPV1 modulation. | |||
Structural insights into TRPA1 and TRPV1 modulation by flavonoid glycosides from licorice for cough relief.,Yi Y, Duan G, Dai Z, Zhou X, Huang J, Jin Z, Yang A, Li Y, Huang Z, Ye M Phytomedicine. 2026 Jun 17;159:158419. doi: 10.1016/j.phymed.2026.158419. PMID:42335638<ref>PMID:42335638</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 9vu0" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Min YM]] | |||
[[Category: Yang YY]] | |||
[[Category: Zonglin DZ]] | |||
