PiTX-K
es/gifchars/alpha.gif" BORDER=0>, a 35-r
esidue peptide recently isolated from the venomof
Pandinus imperator, blocksthe rapidly inactivating (A-type) K
+ channel(s) inrat brain synaptosom
es and the cloned Kv1.2 potassiumchannel at very low toxin concentrations (6 nM and 32 pM, r
espectively)[
Rogowski, R. S., Collins, J.H., O'Neil, T. J., Gustafson, T. A., Werkman, T. A., Rogawski, M. A.,Tenenholz, T. C., Weber, D. J.,& Blaustein, M. P. (1996)
Mol. Pharmacol. 50,1167-1177]. The three-dimensional structure ofPiTX-K
es/gifchars/alpha.gif" BORDER=0> was determined using NMR spectroscopy in order to understand itsselectivity and affinity towardK
+ channels. PiTX-K
es/gifchars/alpha.gif" BORDER=0> was found to have an
es/gifchars/alpha.gif" BORDER=0>-helix from r
esidu
es 10 to 21 and two
es/gifchars/beta2.gif" BORDER=0 ALIGN="middle">-strands(
es/gifchars/beta2.gif" BORDER=0 ALIGN="middle">I,26-28;
es/gifchars/beta2.gif" BORDER=0 ALIGN="middle">II, 33-35) connected by a type II
es/gifchars/beta2.gif" BORDER=0 ALIGN="middle">-turn to form asmall antiparallel
es/gifchars/beta2.gif" BORDER=0 ALIGN="middle">-sheet. Three disulfidebonds, which are conserved in all members of the charybdotoxin family(
es/gifchars/alpha.gif" BORDER=0>-K toxins), anchor one face ofthe
es/gifchars/alpha.gif" BORDER=0>-helix to the
es/gifchars/beta2.gif" BORDER=0 ALIGN="middle">-sheet. The N-terminal portion ofPiTX-K
es/gifchars/alpha.gif" BORDER=0> has three fewer r
esidu
es than other
es/gifchars/alpha.gif" BORDER=0>-Ktoxins such as charybdotoxin. Rather than forming a third
es/gifchars/beta2.gif" BORDER=0 ALIGN="middle">-strand as found for other
es/gifchars/alpha.gif" BORDER=0>-K toxins, theN-terminal region of PiTX-K
es/gifchars/alpha.gif" BORDER=0> adopts an extended conformation.This structural difference in PiTX-K
es/gifchars/alpha.gif" BORDER=0>together with differenc
es in sequence at Pro-10, Tyr-14, and Asn-25(versus Ser-10, Trp-14, and Arg-25in CTX) may explain why PiTX-K
es/gifchars/alpha.gif" BORDER=0> do
es not block maxi-K
+channels. Differenc
es in three-dimensionalstructure between PiTX-K
es/gifchars/alpha.gif" BORDER=0> and charybdotoxin are also observed in boththe tight turn and the loop thatconnects the first
es/gifchars/beta2.gif" BORDER=0 ALIGN="middle">-strand to the
es/gifchars/alpha.gif" BORDER=0>-helix. As a r
esult, sidechains of two r
esidu
es (Tyr-23 and Arg-31)are in regions of PiTX-K
es/gifchars/alpha.gif" BORDER=0> that probably interact with rapidlyinactivating A-type K
+ channels. Theanalogous r
esidu
es in charybdotoxin are positioned differently on thetoxin surface. Thus, the locationsof Tyr-23 and Arg-31 side chains in PiTX-K
es/gifchars/alpha.gif" BORDER=0> could explain why thistoxin blocks A-type channels atmuch lower concentrations than do
es charybdotoxin.