AG 489 explained

AG 489 (or agatoxin 489) is a component of the venom produced by Agelenopsis aperta,^[1] a North American funnel web spider. It inhibits the ligand gated ion channel TRPV₁ through a pore blocking mechanism.^[2]

Discovery

To identify new inhibitors, capsaicin receptor channels (TRPV₁) were screened with a venom library for activity against these channels. In result, the robust inhibitory activity was found in the venom. Venom fractionation using reversed phase HPLC allowed the purification of two acylpolyamine toxins, AG489 and AG505.

Both of these inhibit the TRPV₁ channels^[3] from the extracellular membrane side. From the pore blocking mechanism, the pore mutations that change toxic affinity were identified. As a result, the four mutants decreased toxic affinity and several mutants increased it. Therefore, this was consistent with the scanned TM5-TM6 linker region^[4] being the outer vestibule of the channels and further confirming that AG489 is a pore blocker.

See also

• Agatoxin

Notes and References

1. Herold EE, Yaksh TL . Anesthesia and muscle relaxation with intrathecal injections of AR636 and AG489, two acylpolyamine spider toxins, in rat . Anesthesiology . 77 . 3 . 507–12 . September 1992 . 1519789 . 10.1097/00000542-199209000-00016 .
2. Kitaguchi T, Swartz KJ . An inhibitor of TRPV1 channels isolated from funnel Web spider venom . Biochemistry . 44 . 47 . 15544–9 . November 2005 . 16300403 . 10.1021/bi051494l .
3. Kaneko Y, Szallasi A . Transient receptor potential (TRP) channels: a clinical perspective . British Journal of Pharmacology . 171 . 10 . 2474–507 . May 2014 . 24102319 . 4008995 . 10.1111/bph.12414 .
4. Winter Z, Buhala A, Ötvös F, Jósvay K, Vizler C, Dombi G, Szakonyi G, Oláh Z . 6 . Functionally important amino acid residues in the transient receptor potential vanilloid 1 (TRPV1) ion channel--an overview of the current mutational data . Molecular Pain . 9 . 30 . June 2013 . 23800232 . 3707783 . 10.1186/1744-8069-9-30 . free .