|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.
- 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 and 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.