1djt

Structural highlights

Function

SCM1_MESMA Alpha toxins bind voltage-independently at site-3 of sodium channels (Nav) and inhibit the inactivation of the activated channels thereby blocking neuronal transmission. This toxin is active against both mammals and insects, and is classified as an alpha-like toxin. It is active on Nav1.2/SCN2A (EC(50)=139-252 nM), Nav1.3/SCN3A (EC(50)=565 nM), Nav1.4/SCN4A and Nav1.5/SCN5A (EC(50)=195-500 nM), Nav1.6/SCN8A (EC(50)=214 nM), and drosophila DmNav1 (EC(50)=30 nM) (PubMed:11322948, PubMed:12705833, PubMed:15677695, PubMed:19162162, PubMed:20678086). In mNav1.6/SCN8A, the toxin induces a large increase in both transient and persistent currents, which correlates with a prominent reduction in the fast component of inactivating current (PubMed:20678086). In rNav1.2/SCN2A and rNav1.3/SCN3A, toxin-increased currents is much smaller (PubMed:19162162, PubMed:20678086). Moreover, the toxin only accelerates the slow inactivation development and delay recovery of mNav1.6/SCN8A through binding to the channel in the open state (PubMed:20678086). Is 6-fold more toxic than BmK-M2. In vivo, intrahippocampal injection into rat induces epileptiform responses (PubMed:16229835). In addition, intraplantar injection into rat induces spontaneous nociception and hyperalgesia (PubMed:14554105).^{[1] [2] [3] [4] [5] [6] [7]}

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

References

1. ↑ Goudet C, Huys I, Clynen E, Schoofs L, Wang DC, Waelkens E, Tytgat J. Electrophysiological characterization of BmK M1, an alpha-like toxin from Buthus martensi Karsch venom. FEBS Lett. 2001 Apr 20;495(1-2):61-5. PMID:11322948
2. ↑ Wang CG, Gilles N, Hamon A, Le Gall F, Stankiewicz M, Pelhate M, Xiong YM, Wang DC, Chi CW. Exploration of the functional site of a scorpion alpha-like toxin by site-directed mutagenesis. Biochemistry. 2003 Apr 29;42(16):4699-708. PMID:12705833 doi:http://dx.doi.org/10.1021/bi0270438
3. ↑ Bai ZT, Zhang XY, Ji YH. Fos expression in rat spinal cord induced by peripheral injection of BmK I, an alpha-like scorpion neurotoxin. Toxicol Appl Pharmacol. 2003 Oct 1;192(1):78-85. PMID:14554105 doi:10.1016/s0041-008x(03)00260-6
4. ↑ Liu LH, Bosmans F, Maertens C, Zhu RH, Wang DC, Tytgat J. Molecular basis of the mammalian potency of the scorpion alpha-like toxin, BmK M1. FASEB J. 2005 Apr;19(6):594-6. PMID:15677695 doi:10.1096/fj.04-2485fje
5. ↑ Bai ZT, Zhao R, Zhang XY, Chen J, Liu T, Ji YH. The epileptic seizures induced by BmK I, a modulator of sodium channels. Exp Neurol. 2006 Jan;197(1):167-76. PMID:16229835 doi:10.1016/j.expneurol.2005.09.006
6. ↑ Zhu MM, Tan M, Cheng HW, Ji YH. The alpha-like scorpion toxin BmK I enhances membrane excitability via persistent sodium current by preventing slow inactivation and deactivation of rNav1.2a expressed in Xenopus Oocytes. Toxicol In Vitro. 2009 Jun;23(4):561-8. PMID:19162162 doi:10.1016/j.tiv.2008.12.022
7. ↑ He H, Liu Z, Dong B, Zhou J, Zhu H, Ji Y. Molecular determination of selectivity of the site 3 modulator (BmK I) to sodium channels in the CNS: a clue to the importance of Nav1.6 in BmK I-induced neuronal hyperexcitability. Biochem J. 2010 Oct 15;431(2):289-98. PMID:20678086 doi:10.1042/BJ20100517