Photolabeled sites with a tetrodotoxin derivative in the domain III and IV of the electroplax sodium channel

Saxitoxin

“…[141] Modification of the C11 alcohol, which includes oxidative C6,C11 cleavage to give the C6ketone, is possible and has been exploited to prepare a TTXphotoaffinity probe. [142] Protein labeling experiments with this molecule, however, do not reveal specific details of the toxin binding site, as photochemical cross-linking is found to occur at multiple locations.…”

Saxitoxin

“…[141] Die Modifizierung des C11-Alkohols, die eine oxidative C6,C11-Spaltung zum C6-Keton umfasst, ist mçglich und wurde zur Herstellung eines TTX-Photoaffinitätssensors genutzt. [142] Proteinmarkierungsversuche mit dieser Verbindung ließen jedoch keine spezifischen Details der Toxinbindungsstelle erkennen, da die photochemische Verknüpfung an mehreren Orten erfolgte.…”

Cloning and Distribution of a Putative Tetrodotoxin-Resistant Na+Channel in Newt Retina

“…The TTX-binding sites of Na + channels are thought to be located near the extracellular mouth of the channel, and to contain negatively charged functional groups, because of the inhibition of TTX-binding by carboxyl-modifying reagents (Baker and Rubinson, 1975), some monovalent cations, divalent metal ions, and protons (Henderson et al, 1974). Photoaffinity labeling experiments suggested that the S5-S6 loops of repeats III and IV jointly form part of the TTXbinding site (Nakayama et al, 1992). In site directed mutagenesis experiments, the negatively charged residues at the 2 nd and 5 th positions in the SS2 region of repeats were identified as a major determinant of TTX sensitivity, because single amino acid mutations at these positions strongly reduce the TTX sensitivity (Terlau et al, 1991).…”