Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Human TRPV1 structure and inhibition by the analgesic SB-366791.
Journal, issue, pages	Nat Commun, Vol. 14, Issue 1, Page 2451, Year 2023
Publish date	Apr 28, 2023
Authors	Arthur Neuberger / Mai Oda / Yury A Nikolaev / Kirill D Nadezhdin / Elena O Gracheva / Sviatoslav N Bagriantsev / Alexander I Sobolevsky /
PubMed Abstract	Pain therapy has remained conceptually stagnant since the opioid crisis, which highlighted the dangers of treating pain with opioids. An alternative addiction-free strategy to conventional painkiller- ...Pain therapy has remained conceptually stagnant since the opioid crisis, which highlighted the dangers of treating pain with opioids. An alternative addiction-free strategy to conventional painkiller-based treatment is targeting receptors at the origin of the pain pathway, such as transient receptor potential (TRP) ion channels. Thus, a founding member of the vanilloid subfamily of TRP channels, TRPV1, represents one of the most sought-after pain therapy targets. The need for selective TRPV1 inhibitors extends beyond pain treatment, to other diseases associated with this channel, including psychiatric disorders. Here we report the cryo-electron microscopy structures of human TRPV1 in the apo state and in complex with the TRPV1-specific nanomolar-affinity analgesic antagonist SB-366791. SB-366791 binds to the vanilloid site and acts as an allosteric hTRPV1 inhibitor. SB-366791 binding site is supported by mutagenesis combined with electrophysiological recordings and can be further explored to design new drugs targeting TRPV1 in disease conditions.
External links	Nat Commun / PubMed:37117175 / PubMed Central
Methods	EM (single particle)
Resolution	2.29 - 2.9 Å
Structure data	29981 8gf8 EMDB-29981, PDB-8gf8: Cryo-EM structure of human TRPV1 in cNW11 nanodisc and soybean lipids Method: EM (single particle) / Resolution: 2.9 Å 29982 8gf9 EMDB-29982, PDB-8gf9: Cryo-EM structure of human TRPV1 in cNW11 nanodisc and POPC:POPE:POPG lipids Method: EM (single particle) / Resolution: 2.58 Å 29983 8gfa EMDB-29983, PDB-8gfa: Cryo-EM structure of human TRPV1 in complex with the analgesic drug SB-366791 Method: EM (single particle) / Resolution: 2.29 Å
Chemicals	ChemComp-POV: (2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(trimethylammonio)ethyl phosphate / phospholipidYM / POPC ChemComp-8IJ: (2R)-3-{[(R)-hydroxy{[(1S,2R,3R,4S,5S,6R)-2,3,4,5,6-pentahydroxycyclohexyl]oxy}phosphoryl]oxy}propane-1,2-diyl dioctadecanoate ChemComp-NA: Unknown entry ChemComp-HOH: WATER / Water ChemComp-ZEI: (2E)-3-(4-chlorophenyl)-N-(3-methoxyphenyl)prop-2-enamide ChemComp-DU0*: 2-[2-[(1~{S},2~{S},4~{S},5'~{R},6~{R},7~{S},8~{R},9~{S},12~{S},13~{R},16~{S})-5',7,9,13-tetramethylspiro[5-oxapentacyclo[10.8.0.0^{2,9}.0^{4,8}.0^{13,18}]icos-18-ene-6,2'-oxane]-16-yl]oxyethyl]propane-1,3-diol
Source	homo sapiens (human)
Keywords	MEMBRANE PROTEIN / transient receptor potential V family member 1 / vanilloid / TRP / apo / human / channel / TRPV1 / TRP channels / pain / cNW11 / nanodiscs / thermo-TRP / temperature sensation / POPC:POPE:POPG / inhibition / antagonist / analgesic / drug / SB-366791 / GDN / detergent / glyco-diosgenin