| Structural highlights
Function
[KAX62_SCOMA] Blocks voltage-gated potassium channels (Shaker B, and Kv1.2/KCNA2 (IC(50)=0.8 nM)) and is also active on Kv1.1/KCNA1 (IC(50)=45 nM) Kv1.3/KCNA3 (IC(50)=180 nM). Also inhibits apamin-sensitive small conductance calcium-activated potassium (SK/KCNN) channels, and inhibits intermediate conductance calcium-activated potassium (KCa3.1/KCNN4) channels.[1] [2] [3] [4] [5]
Publication Abstract from PubMed
Maurotoxin (MTX), purified from the scorpionid Scorpio maurus is a potent ligand for potassium channels. It shows a broad specificity as being active on Kv1.1 (Kd = 37 nM), Kv1.2 (Kd = 0.8 nM), Kv1.3 (Kd = 150 nM) voltage-gated potassium channels, as well as on small-conductance calcium-activated potassium channels. It has a unique disulfide pairing among the scorpion toxins family. The solution structure of MTX has been determined by 2D-NMR techniques, which led to the full description of its 3D conformation: a bended helix from residues 6 to 16 connected by a loop to a two-stranded antiparallel beta sheet (residues 23 to 26 and 28 to 31). The interaction of MTX with the pore region of the Kv1.2 potassium channel has been modeled according to their charge anisotropy. The structure of MTX is similar to other short scorpion toxins despite its peculiar disulfide pairing. Its interaction with the Kv1.2 channel involves a dipole moment, which guides and orients the toxin onto the pore, toward the binding site, and which thus is responsible for the specificity.
Solution structure of maurotoxin, a scorpion toxin from Scorpio maurus, with high affinity for voltage-gated potassium channels.,Blanc E, Sabatier JM, Kharrat R, Meunier S, el Ayeb M, Van Rietschoten J, Darbon H Proteins. 1997 Nov;29(3):321-33. PMID:9365987[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Avdonin V, Nolan B, Sabatier JM, De Waard M, Hoshi T. Mechanisms of maurotoxin action on Shaker potassium channels. Biophys J. 2000 Aug;79(2):776-87. PMID:10920011 doi:http://dx.doi.org/10.1016/S0006-3495(00)76335-1
- ↑ Castle NA, London DO, Creech C, Fajloun Z, Stocker JW, Sabatier JM. Maurotoxin: a potent inhibitor of intermediate conductance Ca2+-activated potassium channels. Mol Pharmacol. 2003 Feb;63(2):409-18. PMID:12527813
- ↑ Regaya I, Beeton C, Ferrat G, Andreotti N, Darbon H, De Waard M, Sabatier JM. Evidence for domain-specific recognition of SK and Kv channels by MTX and HsTx1 scorpion toxins. J Biol Chem. 2004 Dec 31;279(53):55690-6. Epub 2004 Oct 21. PMID:15498765 doi:M410055200
- ↑ Kharrat R, Mabrouk K, Crest M, Darbon H, Oughideni R, Martin-Eauclaire MF, Jacquet G, el Ayeb M, Van Rietschoten J, Rochat H, Sabatier JM. Chemical synthesis and characterization of maurotoxin, a short scorpion toxin with four disulfide bridges that acts on K+ channels. Eur J Biochem. 1996 Dec 15;242(3):491-8. PMID:9022673
- ↑ Kharrat R, Mansuelle P, Sampieri F, Crest M, Oughideni R, Van Rietschoten J, Martin-Eauclaire MF, Rochat H, El Ayeb M. Maurotoxin, a four disulfide bridge toxin from Scorpio maurus venom: purification, structure and action on potassium channels. FEBS Lett. 1997 Apr 14;406(3):284-90. PMID:9136903
- ↑ Blanc E, Sabatier JM, Kharrat R, Meunier S, el Ayeb M, Van Rietschoten J, Darbon H. Solution structure of maurotoxin, a scorpion toxin from Scorpio maurus, with high affinity for voltage-gated potassium channels. Proteins. 1997 Nov;29(3):321-33. PMID:9365987
|
