1JLZ

Solution Structure of a K+-Channel Blocker from the Scorpion Toxin of Tityus cambridgei

Summary for 1JLZ

• Entry DOI: 10.2210/pdb1jlz/pdb
• NMR Information: BMRB: 5082
• Descriptor: Tityustoxin alpha-KTx (1 entity in total)
• Functional Keywords: scorpion venom, alpha-ktx, k+-channel blocker, toxin
• Cellular location: Secreted: P83243
• Total number of polymer chains: 1
• Total formula weight: 2461.03

Authors

Wang, I.,Wu, S.-H.,Chang, H.-K.,Shieh, R.-C.,Yu, H.-M.,Chen, C. (deposition date: 2001-07-17, release date: 2002-02-06, Last modification date: 2024-10-09)

Primary citation

Wang, I.,Wu, S.H.,Chang, H.K.,Shieh, R.C.,Yu, H.M.,Chen, C.
Solution structure of a K(+)-channel blocker from the scorpion Tityus cambridgei.
Protein Sci., 11:390-400, 2002

PubMed Abstract: A new K(+)-channel blocking peptide identified from the scorpion venom of Tityus cambridgei (Tc1) is composed of 23 amino acid residues linked with three disulfide bridges. Tc1 is the shortest known toxin from scorpion venom that recognizes the Shaker B K(+) channels and the voltage-dependent K(+) channels in the brain. Synthetic Tc1 was produced using solid-phase synthesis, and its activity was found to be the same as that of native Tc1. The pairings of three disulfide bridges in the synthetic Tc1 were identified by NMR experiments. The NMR solution structures of Tc1 were determined by simulated annealing and energy-minimization calculations using the X-PLOR program. The results showed that Tc1 contains an alpha-helix and a 3(10)-helix at N-terminal Gly(4)-Lys(10) and a double-stranded beta-sheet at Gly(13)-Ile(16) and Arg(19)-Tyr(23), with a type I' beta-turn at Asn(17)-Gly(18). Superposition of each structure with the best structure yielded an average root mean square deviation of 0.26 +/- 0.05 A for the backbone atoms and of 1.40 +/- 0.23 A for heavy atoms in residues 2 to 23. The three-dimensional structure of Tc1 was compared with two structurally and functionally related scorpion toxins, charybdotoxin (ChTx) and noxiustoxin (NTx). We concluded that the C-terminal structure is the most important region for the blocking activity of voltage-gated (Kv-type) channels for scorpion K(+)-channel blockers. We also found that some of the residues in the larger scorpion K(+)-channel blockers (31 to 40 amino acids) are not involved in K(+)-channel blocking activity.

PubMed: 11790849
DOI: 10.1110/ps.33402

Experimental method

SOLUTION NMR