User:Ane.Mana/sandbox
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| Names | |
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| Other names | |
| Identifiers | |
| Properties | |
| C169H267N53 O48 S7 | |
| Molar mass | 4.033,71 g/mol |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Pandinotoxins are scorpion-toxins, purified from the venom of scorpion Pandinus imperator. They are selective blockers of voltage-gated potassium ion channels [1]
Table of contents -1.Source -2.Chemistry: 2.1 Family 2.2 Structure and Homology 2.2.1 Pandinotoxin K α and β 2.2.2 Pandinotoxin K γ -3.Target -4.Mode of action -5.Toxicity -6.Therapeutic use -7.Treatment -8.References
1.Source
Pandinotoxins are derived from the venom of the Pandinus imperator scorpion. [1]
2.Chemistry
2.1 Family The toxins of the family are designated Pandinotoxin (PiTX) K α, PiTX-K β, and PiTX-K γ.[2] They are members of the Charybdotoxin family (α-Kx family) of proteins. [1]
2.2 Structure and Homology 2.2.1 Pandinotoxin K α 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-K α and a glutamic acid in PiTX-K β [2] (see Fig.1).
PiTX-K α and PiTX-K β 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 26-28, β 2 is from 33-35). One face of the α-helix has been anchored to the β-sheet by three sulphide bonds which are conserved in all members of the charybdotoxin family (R-K toxins). [1].
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 [1].
2.2.2 Pandinotoxin K γ Pandinotoxin K γ is not investigated yet.
3. Target
Pandinotoxins are the most potent inhibitors of the rapidly inactivating A-type Ca2+-independent voltage-gated potassium channels [3], 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 ( Shaker gene ) potassium-channels (Kv1.1 sub-family) [4].
4. 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 [5] and it is responsible for the interaction with A-type channels by being inserted in the pore of the ion channels [1].
The structural differences in the backbone and side chain between PiTX-K α and CTX result in a higher affinity for A-type channels for PiTX-K α [1].
The affinity for the Shaker B K+ channel is significantly smaller for PiTX-K β in comparison with PiTX-K α due to the changes in the seventh residue [4].
5. Toxicity No toxic effects have been found yet.
6. Therapeutic use PiTX are used in cancer therapy. Intraplantarly injection of PiTX-K α before or after the administration of diclofenac produces a significant reduction in spontaneous flinching, mechanical allodynia and thermal hyperalgesia in bone cancer rats. Downregulation of PiTX-K α almost completely eliminates diclofenac-induced anti-nociception [6].
7. Treatment This is not known yet.
| The Sequence alignment of the Pandinotoxins |
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CTXN - Ala - Asp - Val - Pro - Gly - Asn - Tyr - Pro - Leu - Asp - Lys - Asp - Gly - Asn - Thr - Tyr - Thr - Cys - Leu - Glu - Leu - Gly - Glu - Asn - Lys - Asp - Cys - Gln - Lys - Val - Cys - Lys - Leu - His - Gly - Val - Gln - Tyr - Gly - Tyr - Cys - Tyr - Ala - Phe - Ser - Cys - Trp - Cys - Lys - Glu - Tyr - Leu - Asp - Asp - Lys - Asp - Ser - Val - OH |