9vu1

Structure of hTRPA1 complexed with LIQA

spinqualitylabelsall models 9vu1, resolution 2.59Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9vu1 is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 2.59Å Ligands: A1ETS Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease TRPA1_HUMAN Familial episodic pain syndrome with predominantly upper body involvement. The disease is caused by mutations affecting the gene represented in this entry. Function TRPA1_HUMAN Receptor-activated non-selective cation channel involved in detection of pain and possibly also in cold perception and inner ear function (PubMed:25389312, PubMed:25855297). Has a central role in the pain response to endogenous inflammatory mediators and to a diverse array of volatile irritants, such as mustard oil, cinnamaldehyde, garlic and acrolein, an irritant from tears gas and vehicule exhaust fumes (PubMed:25389312, PubMed:20547126). Is also activated by menthol (in vitro)(PubMed:25389312). Acts also as an ionotropic cannabinoid receptor by being activated by delta(9)-tetrahydrocannabinol (THC), the psychoactive component of marijuana (PubMed:25389312). May be a component for the mechanosensitive transduction channel of hair cells in inner ear, thereby participating in the perception of sounds. Probably operated by a phosphatidylinositol second messenger system (By similarity).[UniProtKB:Q8BLA8] 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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