8GFA
Cryo-EM structure of human TRPV1 in complex with the analgesic drug SB-366791
Summary for 8GFA
| Entry DOI | 10.2210/pdb8gfa/pdb |
| Related | 8GF8 8GF9 |
| EMDB information | 29981 29982 29983 |
| Descriptor | Transient receptor potential cation channel subfamily V member 1, (2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(trimethylammonio)ethyl phosphate, (2E)-3-(4-chlorophenyl)-N-(3-methoxyphenyl)prop-2-enamide, ... (6 entities in total) |
| Functional Keywords | transient receptor potential v family member 1, trp, human, channel, inhibition, antagonist, trpv1, trp channels, pain, analgesic, drug, membrane protein, sb-366791, thermo-trp, temperature sensation, vanilloid, gdn, detergent, glyco-diosgenin |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 4 |
| Total formula weight | 528927.81 |
| Authors | Neuberger, A.,Nadezhdin, K.D.,Sobolevsky, A.I. (deposition date: 2023-03-07, release date: 2023-05-10, Last modification date: 2024-10-23) |
| Primary citation | Neuberger, A.,Oda, M.,Nikolaev, Y.A.,Nadezhdin, K.D.,Gracheva, E.O.,Bagriantsev, S.N.,Sobolevsky, A.I. Human TRPV1 structure and inhibition by the analgesic SB-366791. Nat Commun, 14:2451-2451, 2023 Cited by 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-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. PubMed: 37117175DOI: 10.1038/s41467-023-38162-9 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.29 Å) |
Structure validation
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