molecular target
Toxin Project – Target Structure Toxin: Aconitine
Sabrina Lugo UCI ID# 69573152 Chem 128 July 14, 2014
Voltage gated sodium channels mediate the amount of sodium entering the cell. This action of mediation is what underlines the depolarization of the membrane potential, which leads to action potentials being released in the neurons and excitable cells such as skeletal muscles, and cardiac tissue. Aconitine is a lipid-‐soluble toxin which binds to site 2 of the alpha-‐subunit of the voltage-‐gated sodium channel. Site 2 is believed to be located mainly at the S6 of the domains. Known as an activator, Aconitine prolongs the channels to maintain their open state, allowing a large amount of sodium ions to enter the cell leading to a prolonged depolarization of the cell membrane. Binding causes the sodium channel to open more easily and stay open longer by shifting the voltage dependence of
activation towards a more negative potential. Recent evidence has suggested that site 2 toxins bind within the inner pore resides in the S6 segments of the domains (Stevens, et.al., 2011). References: Aconitine. http://en.wikipedia.org/wiki/Aconitine. Aconitine. IUPHAR database. http://www.iuphar-‐ db.org/DATABASE/LigandDisplayForward?tab=biology&ligandId=2617. Blasius, A., Dubin, A., Petrus, M., Lim, B., Narezkina, A., Criado, J., Wills, D., Xia, Y., Ehlers, C., Knowlton, K., Patapoutian, A., Beutler, B. A database of mutations and phenotypes induced by ENU: background. Mutagenetix. http://mutagenetix.utsouthwestern.edu/phenotypic/phenotypic_rec.cfm?pk =258 Marban, E., Yamagishi, T., Tomaselli, G. Structure and function of voltage-‐gated sodium channels. Journal of Physiology. Vol. 508:3. 1998. 647-‐657. Payandeh, J., Scheuer, T., Zheng, N., Catteral, W. The crystal structure of a voltage-‐ gated sodium channel. Nature. Vol. 475. 2011. 353-‐358 Stevens, M., Peignar, S., Tytgat, J. Neurotoxins and their binding areas on voltage-‐ gated sodium channels. Frontiers in Pharmacology. Vol. 2:71. 2011. 1-‐13. Voltage-‐gated Sodium Channel. http://en.wikipedia.org/wiki/Sodium_channel. Wang, S., Wang, G. Voltage-‐gated sodium channels as primary targets of diverse lipid-‐ soluble neurotoxins. Cellular Signaling. Vol. 15. 2003. 151-‐159.
Sabrina Lugo UCI ID# 69573152 Chem 128 July 14, 2014
Voltage gated sodium channels mediate the amount of sodium entering the cell. This action of mediation is what underlines the depolarization of the membrane potential, which leads to action potentials being released in the neurons and excitable cells such as skeletal muscles, and cardiac tissue. Aconitine is a lipid-‐soluble toxin which binds to site 2 of the alpha-‐subunit of the voltage-‐gated sodium channel. Site 2 is believed to be located mainly at the S6 of the domains. Known as an activator, Aconitine prolongs the channels to maintain their open state, allowing a large amount of sodium ions to enter the cell leading to a prolonged depolarization of the cell membrane. Binding causes the sodium channel to open more easily and stay open longer by shifting the voltage dependence of
activation towards a more negative potential. Recent evidence has suggested that site 2 toxins bind within the inner pore resides in the S6 segments of the domains (Stevens, et.al., 2011). References: Aconitine. http://en.wikipedia.org/wiki/Aconitine. Aconitine. IUPHAR database. http://www.iuphar-‐ db.org/DATABASE/LigandDisplayForward?tab=biology&ligandId=2617. Blasius, A., Dubin, A., Petrus, M., Lim, B., Narezkina, A., Criado, J., Wills, D., Xia, Y., Ehlers, C., Knowlton, K., Patapoutian, A., Beutler, B. A database of mutations and phenotypes induced by ENU: background. Mutagenetix. http://mutagenetix.utsouthwestern.edu/phenotypic/phenotypic_rec.cfm?pk =258 Marban, E., Yamagishi, T., Tomaselli, G. Structure and function of voltage-‐gated sodium channels. Journal of Physiology. Vol. 508:3. 1998. 647-‐657. Payandeh, J., Scheuer, T., Zheng, N., Catteral, W. The crystal structure of a voltage-‐ gated sodium channel. Nature. Vol. 475. 2011. 353-‐358 Stevens, M., Peignar, S., Tytgat, J. Neurotoxins and their binding areas on voltage-‐ gated sodium channels. Frontiers in Pharmacology. Vol. 2:71. 2011. 1-‐13. Voltage-‐gated Sodium Channel. http://en.wikipedia.org/wiki/Sodium_channel. Wang, S., Wang, G. Voltage-‐gated sodium channels as primary targets of diverse lipid-‐ soluble neurotoxins. Cellular Signaling. Vol. 15. 2003. 151-‐159.
