Trp: a conserved aromatic residue crucial to the interaction of a scorpion peptide with sodium channels.
Anti-tumour-analgesic peptide (AGAP), one scorpion toxin purified from Buthus martensii Karsch, was known as its analgesic and anti-tumour activities. Trp38, a conserved aromatic residue of AGAP, might play important roles in its interaction with sodium channels. In this study, a mutant W38F was generated and effects of W38F were examined on hNav1.4, hNav1.5 and hNav1.7 by using whole-cell patch-clamp, which were closely associated to the biotoxicity of skeletal and cardiac muscles and pain signalling. The data showed that W38F decreased the inhibition effects of peak currents of hNav1.7, hNav1.4 and hNav1.5 compared with AGAP, notably, W38F reduced the analgesic activity compared with AGAP. The results suggested that Trp38 be a crucial amino acid involved in the interaction with these three sodium channels. The decreased analgesic activity of W38F might result from its much less inhibition of hNav1.7. These findings provided more information about the relationship between structure and function of AGAP and may facilitate the modification of other scorpion toxins with pharmacological effects.
['Xu|Yijia|Y|', 'Sun|Jianfang|J|', 'Yu|Yue|Y|', 'Kong|Xiaohua|X|', 'Meng|Xiangxue|X|', 'Liu|Yanfeng|Y|', 'Cui|Yong|Y|', 'Su|Yang|Y|', 'Zhao|Mingyi|M|', 'Zhang|Jinghai|J|']
D000700:Analgesics D000818:Animals D005260:Female D006801:Humans D015640:Ion Channel Gating D008297:Male D051379:Mice D062553:NAV1.4 Voltage-Gated Sodium Channel D062554:NAV1.5 Voltage-Gated Sodium Channel D062556:NAV1.7 Voltage-Gated Sodium Channel D010146:Pain D010446:Peptide Fragments D012604:Scorpion Venoms D014364:Tryptophan
AGAP scorpion toxin analgesic activity Nav1.7 voltage-gated sodium channel