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Lq2 is a component of the venom of the scorpion Leiurus quinquestriatus. It blocks various potassium channels, among others the inward-rectifier potassium ion channel ROMK1.[1]

Lq2

Contents

Alternative names

Lq2 is also known as Potassium channel toxin alpha-KTx 1.2, Charybdotoxin-2, ChTX-Lq2, ChTx-d, Toxin 18-2 or Lqh 18-2.

Etymology

The name Lq2 refers to the name of the animal species in which the toxin can be found.[2] Lq2 can be found in the scorpion Leiurus quinquestriatus (Lq).[3][4] Lq2 is structurally similar to Lq1, which had been found previously and which is also a potassium channel blocker.

Source

Lq2 is a component of the venom of the scorpion Leiurus quinquestriatus, known under various names, for example the deathstalker, the Israeli desert scorpion or the yellow scorpion.

Structure

Lq2 is a small peptide of 59 amino acids. Lq2 contains the classical scorpion toxin alpha-beta scaffold and is structurally similar to the neurotoxin Charybdotoxin (CTX).[5] Lq2 consists of an α-helix and a β-sheet, connected by an αβ3 loop containing disulfide bridges. The proteins three-dimensional structure has been reconstructed using nuclear magnetic resonance techniques.[5]

Target

Lq2 interacts with all three types of potassium channels:[6] the voltage-activated, the Ca2+- activated and the inward-rectifier potassium channels.[7] The unique trait of Lq2 is its high affinity for certain inward-rectifier potassium ion channels, especially the Renal Outer Medullary Potassium channel ROMK1. This ion channel contributes to the regulation of the resting membrane potential.

Mode of action

Since all potassium channels share the same ion conducting outer pore structure, Lq2 binds to all three potassium channel types. Lq2 interacts with the T-X-X-T-X-GT-X-X-T-X-GY/F-Gt K+-selective section within the pore-forming region (P-region) of the ROMK1 ion channel. It blocks the channel, binding in a 1:1 stoichiometric ratio with its β-sheet.[8]

Therapeutic use

Potential use of Lq2 is mainly in cardiovascular diseases.[3]

References

  1. ^ Kubo Y, Adelman JP, Clapham DE, et al. (December 2005). "International Union of Pharmacology. LIV. Nomenclature and molecular relationships of inwardly rectifying potassium channels". Pharmacological Reviews 57 (4): 509–26. doi:10.1124/pr.57.4.11. PMID 16382105.  
  2. ^ Catterall WA, Cestèle S, Yarov-Yarovoy V, Yu FH, Konoki K, Scheuer T (February 2007). "Voltage-gated ion channels and gating modifier toxins". Toxicon : Official Journal of the International Society on Toxinology 49 (2): 124–41. doi:10.1016/j.toxicon.2006.09.022. PMID 17239913.  
  3. ^ a b Cui M, Shen J, Briggs JM, et al. (April 2001). "Brownian dynamics simulations of interaction between scorpion toxin Lq2 and potassium ion channel". Biophysical Journal 80 (4): 1659–69. doi:10.1016/S0006-3495(01)76138-3. PMID 11259281.  
  4. ^ MacKinnon R, Cohen SL, Kuo A, Lee A, Chait BT (April 1998). "Structural conservation in prokaryotic and eukaryotic potassium channels". Science 280 (5360): 106–9. doi:10.1126/science.280.5360.106. PMID 9525854.  
  5. ^ a b Renisio JG, Lu Z, Blanc E, et al. (March 1999). "Solution structure of potassium channel-inhibiting scorpion toxin Lq2". Proteins 34 (4): 417–26. doi:10.1002/(SICI)1097-0134(19990301)34:4<417::AID-PROT1>3.0.CO;2-R. PMID 10081954.  
  6. ^ Isomoto S, Kondo C, Kurachi Y (February 1997). "Inwardly rectifying potassium channels: their molecular heterogeneity and function". The Japanese Journal of Physiology 47 (1): 11–39. doi:10.2170/jjphysiol.47.11. PMID 9159640.  
  7. ^ Neusch C, Weishaupt JH, Bähr M (February 2003). "Kir channels in the CNS: emerging new roles and implications for neurological diseases". Cell and Tissue Research 311 (2): 131–8. doi:10.1007/s00441-002-0669-x. PMID 12596033.  
  8. ^ Lu Z, MacKinnon R (June 1997). "Purification, characterization, and synthesis of an inward-rectifier K+ channel inhibitor from scorpion venom". Biochemistry 36 (23): 6936–40. doi:10.1021/bi9702849. PMID 9188688.  
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