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8.B.30.  The Diguetoxin (Diguetoxin) Family

Insecticidal toxins frequently target voltage-gated cation channels (TC# 1.A.1) (Krapcho et al. 1995, Bloomquist et al. 1996). One such toxin, Dc1a, promotes opening of insect Nav channels. The toxin binds to the S1-S2 and S3-S4 loops in the domain II voltage-sensor (i.e., receptor site 4). The American cockroach P.americana is largely resistant to the effects of this toxin due to an unusual sequence within the domain II S1-S2 loop. In vivo, the toxin paralyzes lepidopteran and dipteran larvae. Paralyzed insects ultimately die from secondary effects of starvation and dehydration (Bende et al. 2014). The toxin has no effect on the human Nav channel subtypes Nav1.1 - Nav1.7, and has no effect on hERG (Kv11.1) and Kv2.1. It is non-toxic to mice (Bende et al. 2014).


 

References associated with 8.B.30 family:

Bende, N.S., S. Dziemborowicz, M. Mobli, V. Herzig, J. Gilchrist, J. Wagner, G.M. Nicholson, G.F. King, and F. Bosmans. (2014). A distinct sodium channel voltage-sensor locus determines insect selectivity of the spider toxin Dc1a. Nat Commun 5: 4350. 25014760
Bloomquist, J.R., L.P. Kinne, V. Deutsch, and S.F. Simpson. (1996). Mode of action of an insecticidal peptide toxin from the venom of a weaving spider (Diguetia canities). Toxicon 34: 1072-1075. 8896202
Krapcho, K.J., R.M. Kral, Jr, B.C. Vanwagenen, K.G. Eppler, and T.K. Morgan. (1995). Characterization and cloning of insecticidal peptides from the primitive weaving spider Diguetia canities. Insect Biochem Mol Biol 25: 991-1000. 8541888
Shen, H., Z. Li, Y. Jiang, X. Pan, J. Wu, B. Cristofori-Armstrong, J.J. Smith, Y.K.Y. Chin, J. Lei, Q. Zhou, G.F. King, and N. Yan. (2018). Structural basis for the modulation of voltage-gated sodium channels by animal toxins. Science 362:. 30049784