2pta
From Proteopedia
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PANDINUS TOXIN K-A (PITX-KA) FROM PANDINUS IMPERATOR, NMR, 20 STRUCTURES
Overview
PiTX-K alpha, a 35-residue peptide recently isolated from the venom of, Pandinus imperator, blocks the rapidly inactivating (A-type) K+ channel(s), in rat brain synaptosomes and the cloned Kv 1.2 potassium channel at very, low toxin concentrations (6 nM and 32 pM, respectively) [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 of PiTX-K alpha, was determined using NMR spectroscopy in order to understand its, selectivity and affinity toward K+ channels. PiTX-K alpha was found to, have an alpha-helix from residues 10 to 21 and two beta-strands (betaI, 26-28; betaII, 33-35) connected by a type II beta-turn to form a small, antiparallel beta-sheet. Three disulfide bonds, which are conserved in all, members of the charybdotoxin family (alpha-K toxins), anchor one face of, the alpha-helix to the beta-sheet. The N-terminal portion of PiTX-K alpha, has three fewer residues than other alpha-K toxins such as charybdotoxin., Rather than forming a third beta-strand as found for other alpha-K toxins, the N-terminal region of PiTX-K alpha adopts an extended conformation., This structural difference in PiTX-K alpha together with differences in, sequence at Pro-10, Tyr-14, and Asn-25 (versus Ser-10, Trp-14, and Arg-25, in CTX) may explain why PiTX-K alpha does not block maxi-K+ channels., Differences in three-dimensional structure between PiTX-K alpha and, charybdotoxin are also observed in both the tight turn and the loop that, connects the first beta-strand to the alpha-helix. As a result, side, chains of two residues (Tyr-23 and Arg-31) are in regions of PiTX-K alpha, that probably interact with rapidly inactivating A-type K+ channels. The, analogous residues in charybdotoxin are positioned differently on the, toxin surface. Thus, the locations of Tyr-23 and Arg-31 side chains in, PiTX-K alpha could explain why this toxin blocks A-type channels at much, lower concentrations than does charybdotoxin.
About this Structure
2PTA is a Single protein structure of sequence from Pandinus imperator. Full crystallographic information is available from OCA.
Reference
Solution structure for Pandinus toxin K-alpha (PiTX-K alpha), a selective blocker of A-type potassium channels., Tenenholz TC, Rogowski RS, Collins JH, Blaustein MP, Weber DJ, Biochemistry. 1997 Mar 11;36(10):2763-71. PMID:9062103
Page seeded by OCA on Wed Nov 21 13:39:29 2007
