Nirthanan S, Gopalakrishnakone P, Gwee M C E, Khoo H E, Kini R M
Venom and Toxin Research Programme, Department of Anatomy, Faculty of Medicine, National University of Singapore, Singapore.
Toxicon. 2003 Mar;41(4):397-407. doi: 10.1016/s0041-0101(02)00388-4.
Non-conventional toxins constitute a poorly characterized class of three-finger toxins isolated exclusively from Elapidae venoms. These toxins are monomers of 62-68 amino acid residues and contain five disulfide bridges. However, unlike alpha/kappa-neurotoxins and kappa-neurotoxins which have the fifth disulfide bridge in their middle loop (loop II), the fifth disulfide bridge in non-conventional toxins is located in loop I (N-terminus loop). Overall, non-conventional toxins share approximately 28-42% identity with other three-finger toxins including alpha-neurotoxins, alpha/kappa-neurotoxins and kappa-neurotoxins. Recent structural studies have revealed that non-conventional toxins also display the typical three-finger motif. Non-conventional toxins are typically characterized by a lower order of toxicity (LD(50) approximately 5-80 mg/kg) in contrast to prototype alpha-neurotoxins (LD(50) approximately 0.04-0.3 mg/kg) and hence they are also referred to as 'weak toxins'. Further, it is generally assumed that non-conventional toxins target muscle (alpha(2)beta gamma delta) receptors with low affinities several orders of magnitude lower than alpha-neurotoxins and alpha/kappa-neurotoxins. However, it is now known that some non-conventional toxins also antagonize neuronal alpha 7 nicotinic acetylcholine receptors. Hence, non-conventional toxins are not a functionally homogeneous group and other, yet unknown, molecular targets for this class of snake venom toxins may exist. Non-conventional toxins may therefore be a useful source of ligands with novel biological activity targeting the plethora of neuronal nicotinic receptors as well as other physiological processes.
非传统毒素是一类特征尚不明确的三指毒素，仅从眼镜蛇科毒液中分离得到。这些毒素是由62 - 68个氨基酸残基组成的单体，含有五个二硫键。然而，与在中环（环II）具有第五个二硫键的α/κ-神经毒素和κ-神经毒素不同，非传统毒素的第五个二硫键位于环I（N端环）。总体而言，非传统毒素与其他三指毒素（包括α-神经毒素、α/κ-神经毒素和κ-神经毒素）的同源性约为28 - 42%。最近的结构研究表明，非传统毒素也呈现典型的三指基序。与原型α-神经毒素（半数致死量约为0.04 - 0.3mg/kg）相比，非传统毒素的典型特征是毒性较低（半数致死量约为5 - 80mg/kg），因此它们也被称为“弱毒素”。此外，一般认为非传统毒素以低亲和力靶向肌肉（α2βγδ）受体，其亲和力比α-神经毒素和α/κ-神经毒素低几个数量级。然而，现在已知一些非传统毒素也能拮抗神经元α7烟碱型乙酰胆碱受体。因此，非传统毒素并非功能上的同质群体，这类蛇毒毒素可能还存在其他未知的分子靶点。因此，非传统毒素可能是一类有用的配体来源，具有针对大量神经元烟碱型受体以及其他生理过程的新型生物活性。
