2AXK

Solution structure of discrepin, a scorpion venom toxin blocking K+ channels.

Summary for 2AXK

• Entry DOI: 10.2210/pdb2axk/pdb
• NMR Information: BMRB: 6924
• Descriptor: discrepin (1 entity in total)
• Functional Keywords: discrepin, scorpion toxin, a-current, k+-channel, toxin
• Total number of polymer chains: 1
• Total formula weight: 4189.89

Authors

Prochnicka-Chalufour, A.,Corzo, G.,Satake, H.,Martin-Eauclaire, M.-F.,Murgia, A.R.,Prestipino, G.,D'Suze, G.,Possani, L.D.,Delepierre, M. (deposition date: 2005-09-05, release date: 2006-06-20, Last modification date: 2019-12-25)

Primary citation

Prochnicka-Chalufour, A.,Corzo, G.,Satake, H.,Martin-Eauclaire, M.-F.,Murgia, A.R.,Prestipino, G.,D'Suze, G.,Possani, L.D.,Delepierre, M.
Solution structure of discrepin, a new K+-channel blocking peptide from the alpha-KTx15 subfamily.
Biochemistry, 45:1795-1804, 2006

PubMed Abstract: Discrepin, isolated from the venom of the Venezuelan scorpion Tityus discrepans, blocks preferentially the I(A) currents of the voltage-dependent K+ channel of rat cerebellum granular cells in an irreversible way. It contains 38 amino acid residues with a pyroglutamic acid as the N-terminal residue [D'Suze, G., Batista, C. V., Frau, A., Murgia, A. R., Zamudio, F. Z., Sevcik, C., Possani, L. D., and Prestipino, G. (2004) Arch. Biochem. Biophys. 430, 256-63]. It is the most distinctive member of the alpha-KTx15 subfamily of scorpion toxins. Six members of the alpha-KTx15 subfamily have been reported so far to be specific for this subtype of the K+ channel; however, none of them have had their three-dimensional structure determined, and no information for the residues possibly involved in channel recognition and binding is available. Natural discrepin (n-discrepin) was prepared from scorpion venom, and its synthetic analogue (s-discrepin) was obtained by solid-phase synthesis. Analysis of two-dimensional 1H NMR spectra of n- and s-discrepin indicates that both peptides have the same structure. Here we report the solution structure of s-discrepin determined by NMR using 565 meaningful distance constraints derived from the volume integration of the two-dimensional NOESY spectrum, 22 dihedrals, and three hydrogen bonds. Discrepin displays the alpha/beta scaffold, characteristic of scorpion toxins. Some features of the proposed interacting surface between the toxin and channel as well as the opposite "alpha-helix surface" are discussed in comparison with those of other alpha-KTx15 members. Both n- and s-discrepin exhibit similar physiological actions as verified by patch-clamp and binding and displacement experiments.

PubMed: 16460026
DOI: 10.1021/bi0519248

Experimental method

SOLUTION NMR