Schematic diagram of the three-dimensional of Pandinotoxin
Structure and Homology
|The sequences of Pandinotoxins|
Figure 1: Sequence of Pandinotoxins. Adapted from 
Pandinotoxin Kα and -β
PiTX-Kα and PiTX-Kβ are 35-residue peptides, which are found to have an α-helix from residues 10 to 21 and two β-sheets (β 1 is from residues 26-28, β 2 is from residues 33-35). One face of the α-helix is anchored to the β-sheet by three disulfide bonds which are conserved in all members of the charybdotoxin family (R-K toxins). PiTX-K α and PiTX-K β have only two β-sheets whereas other members of the family have three additional amino acid residues at the N-terminal portion, which forms a third β-sheet.
Pandinotoxin Kγ has not yet been investigated.
Pandinotoxins are the most potent inhibitors of the rapidly inactivating A-type voltage-gated potassium channels. They also block the delayed rectifier, slowly inactivating channels of the subfamily A member 2 (Kv1.2/KCNA2)  and they can reversibly block the Shaker B potassium-channels (Kv1.1 sub-family).
Mode of action
The residue K27, a lysine at place 27 of the protein sequence, interacts with the voltage sensitivity blocking activity of CTX channels. It is conserved among PiTX-K α and PiTX-K β. This amino acid is located nearby the selectivity filter of the pore  and it is responsible for the interaction with A-type channels by being inserted in the pore of the ion channels. The structural differences in the backbone and side chain between PiTX-Kα and CTX result in a higher affinity for A-type channels for PiTX-Kα. The affinity for the Shaker B K+ channel is significantly smaller for PiTX-Kβ in comparison with PiTX-Kα owing to the changes in the seventh residue.
Intraplantarly injection of PiTX-Kα before or after the administration of diclofenac produces a significant reduction in spontaneous flinching, mechanical allodynia and thermal hyperalgesia in a rat model for bone cancer. Downregulation of PiTX-Kα almost completely eliminates diclofenac-induced anti-nociception.
- Tenenholz TC, Rogowski RS, Collins JH, Blaustein MP, Weber DJ (1997). "Solution Structure for Pandinus Toxin K-R (PiTX-KR), a Selective Blocker of A-Type Potassium Channels". Biochemistry. 11;36(10): 2763–71. doi:10.1021/bI9628432. PMID 9062103.
- Rogowski RS; Collins JH; O’Neill TJ; Gustafson TA; Werkman TR; Rogawski MA; Tenenholz TC; Weber DJ; Blaustein MP (1996). "Three new toxins from the scorpion Pandinus imperator selectively block certain voltage-gated K+ channels". Mol Pharmacol. 50 (5): 1167–77. PMID 8913348.
- Klenk KC, Tenenholz TC, Matteson DR, Rogowski RS, Blaustein MP, Weber DJ (2000). "Structural and Functional Differences of Two Toxins From the Scorpion Pandinus Imperator". Proteins. 38 (4): 441–9. doi:10.1002/(sici)1097-0134(20000301)38:4<441::aid-prot9>3.0.co;2-l. PMID 10707030.
- Gómez-Lagunas F, Olamendi-Portugal T, Zamudio FZ, Possani LD (1996). "Two novel toxins from the venom of the scorpion Pandinus imperator show that the N-terminal amino acid sequence is important for their affinities towards Shaker B K+ channels". J Membr Biol. 152 (1): 49–56. doi:10.1007/s002329900084. PMID 8660410.
- H. Darbon, E. Blanc & J.M. Sabatier (1999). "Three-dimensional structure of scorpion toxins: Towards a new model of interaction with potassium channels". Perspectives in Drug Discovery and Design. 15/16: 41–60. doi:10.1023/A:1017070801207.
- -Zheng Duan; Qian Xu; Xiao-Meng Zhang; Zhi-Qi Zhao; Yan-Ai Mei; Yu-Qiu Zhang (2012). "Targeting A-type K+ channels in primary sensory neurons for bone cancer pain in a rat mode". Pain. 153: 562–574. doi:10.1016/j.pain.2011.11.020. PMID 22188869.