8GFA

Cryo-EM structure of human TRPV1 in complex with the analgesic drug SB-366791

8GFA の概要

• エントリーDOI: 10.2210/pdb8gfa/pdb
• 関連するPDBエントリー: 8GF8 8GF9
• EMDBエントリー: 29981 29982 29983
• 分子名称: 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)
• 機能のキーワード: 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
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 528927.81

構造登録者

Neuberger, A.,Nadezhdin, K.D.,Sobolevsky, A.I. (登録日: 2023-03-07, 公開日: 2023-05-10, 最終更新日: 2024-10-23)

主引用文献

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

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: 37117175
DOI: 10.1038/s41467-023-38162-9

実験手法

ELECTRON MICROSCOPY (2.29 Å)