Pandinotoxin
{{Short description|Chemical compound}}
{{Infobox nonhuman protein
| Name = Pandinotoxin
| image = Pandinotoxin.JPG
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| caption = Schematic diagram of the three-dimensional of Pandinotoxin
| Organism = Pandinus imperator
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| Symbol = N/A
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Pandinotoxins are toxins from the venom of the emperor scorpion Pandinus imperator. They are selective blockers of voltage-gated potassium channels
Sources
The source for the pandinotoxins is the venom of the scorpion Pandinus imperator.
Chemistry
=Family=
The toxins of the family are designated pandinotoxin (PiTX)-Kα, PiTX-Kβ, and PiTX-Kγ {{cite journal |author1=Rogowski RS |author2=Collins JH |author3=O’Neill TJ |author4=Gustafson TA |author5=Werkman TR |author6=Rogawski MA |author7=Tenenholz TC |author8=Weber DJ |author9=Blaustein MP |title= Three new toxins from the scorpion Pandinus imperator selectively block certain voltage-gated K+ channels |journal= Mol Pharmacol |volume=50 |pages=1167–77|year=1996|pmid = 8913348 |issue=5}} They are members of the α-KTx family of scorpion toxins.
=Structure and homology=
==Pandinotoxin Kα and -β==
The amino acid sequences of PiTX-K α and PiTX-K β are identical, except for the seventh amino acid: a proline in PiTX-Kα and a glutamic acid in PiTX-Kβ (see Fig.1).
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==
Pandinotoxin Kγ has not yet been investigated.
Target
Pandinotoxins are the most potent inhibitors of the rapidly inactivating A-type voltage-gated potassium channels.{{cite journal |vauthors=Klenk KC, Tenenholz TC, Matteson DR, Rogowski RS, Blaustein MP, Weber DJ |title= Structural and Functional Differences of Two Toxins From the Scorpion Pandinus Imperator |journal= Proteins |volume=38 |pages=441–9 |year=2000|pmid= 10707030 |issue=4 |doi=10.1002/(sici)1097-0134(20000301)38:4<441::aid-prot9>3.0.co;2-l}} They also block the delayed rectifier, slowly inactivating channels of the subfamily A member 2 (Kv1.2/KCNA2) [1] and they can reversibly block the shaker B potassium-channels (Kv1.1 sub-family).{{cite journal |vauthors=Gómez-Lagunas F, Olamendi-Portugal T, Zamudio FZ, Possani LD |title= 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 |journal=J Membr Biol|volume=152 |pages=49–56 |year=1996|pmid=8660410 |issue=1 |doi=10.1007/s002329900084|s2cid= 20551964 }}
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 {{cite journal |author1=H. Darbon, E. Blanc |author2=J.M. Sabatier |name-list-style=amp |title= Three-dimensional structure of scorpion toxins: Towards a new model of interaction with potassium channels |journal= Perspectives in Drug Discovery and Design |volume=15/16 |pages=41–60 |year=1999|doi= 10.1023/A:1017070801207}} 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.
Therapeutic use
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.{{cite journal |author1=-Zheng Duan |author2=Qian Xu |author3=Xiao-Meng Zhang |author4=Zhi-Qi Zhao |author5=Yan-Ai Mei |author6=Yu-Qiu Zhang |title= Targeting A-type K+ channels in primary sensory neurons for bone cancer pain in a rat mode |journal= Pain |volume=153 |pages=562–574|year=2012|issue=3 |pmid= 22188869 |doi=10.1016/j.pain.2011.11.020|s2cid=2042820 }}
References
{{Reflist}}
{{Toxins}}
{{Potassium channel blockers}}