1n8m
From Proteopedia
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Solution structure of Pi4, a four disulfide bridged scorpion toxin active on potassium channels
Overview
Pi4 is a short toxin found at very low abundance in the venom of Pandinus, imperator scorpions. It is a potent blocker of K(+) channels. Like the, other members of the alpha-KTX6 subfamily to which it belongs, it is, cross-linked by four disulfide bonds. The synthetic analog (sPi4) and the, natural toxin (nPi4) have been obtained by solid-phase synthesis or from, scorpion venom, respectively. Analysis of two-dimensional (1)H NMR spectra, of nPi4 and sPi4 indicates that both peptides have the same structure., Moreover, electrophysiological recordings of the blocking of Shaker B K(+), channels by sPi4 (K(D) = 8.5 nM) indicate that sPi4 has the same blocking, activity of nPi4 (K(D) = 8.0 nM), previously described. The disulfide, bonds have been independently determined by NMR and structure, calculations, and by Edman-degradation/mass-spectrometry identification of, peptides obtained by proteolysis of nPi4. Both approaches indicate that, the pairing of the half-cystines is (6)C-(27)C, (12)C-(32)C, (16)C-(34)C, and (22)C-(37)C. The structure of the toxin has been determined by using, 705 constraints derived from NMR data on sPi4. The structure, which is, well defined, shows the characteristic alpha/beta scaffold of scorpion, toxins. It is compared to the structure of the other alpha-KTX6 subfamily, members and, in particular, to the structure of maurotoxin, which shows a, different pattern of disulfide bridges despite its high degree of sequence, identity (76%) with Pi4. The structure of Pi4 and the high amounts of, synthetic peptide available, will enable the detailed analysis of the, interaction of Pi4 with K(+) channels.
About this Structure
1N8M is a Single protein structure of sequence from [1]. Full crystallographic information is available from OCA.
Reference
Solution structure of Pi4, a short four-disulfide-bridged scorpion toxin specific of potassium channels., Guijarro JI, M'Barek S, Gomez-Lagunas F, Garnier D, Rochat H, Sabatier JM, Possani L, Delepierre M, Protein Sci. 2003 Sep;12(9):1844-54. PMID:12930984
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