GiTx1(β/κ-theraphotoxin-Gi1a), a novel toxin from the venom of Brazilian tarantula Grammostola iheringi (Mygalomorphae, Theraphosidae): Isolation, structural assessments and activity on voltage-gated ion channels

Montandon, Gabriela; Cassoli, Juliana S.; Peigneur, Steve; Verano‐Braga, Thiago; Santos, Daniel Moreira dos; Paiva, Ana Luiza Bittencourt; Moraes, Éder Ricardo de; Kushmerick, Christopher; Borges, Márcia Helena; Richardson, Michael; Pimenta, Adriano Monteiro de Castro; Kjeldsen, Frank; Diniz, Marcelo R.V.; Tytgat, Jan; Lima, Maria Elena de

doi:10.1016/j.biochi.2020.07.008

Cited by 1 publication

(2 citation statements)

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“…For example, the Hanatoxin (HaTx1) [72] and HpTx1 [73] (patent) toxins show effect on Ca 2+ and K + channels. On the other hand, the VsTx1 [74], PaTx1 [75,76], HmTx1 [77,78] and GiTx1 [79] toxins have been reported as Na + and K + channel modulators. Furthermore, it has been discovered that in the toxin-channel interaction, the lipids in the cell membrane are also involved [80,81].…”

Section: Gating Modifiers Peptidesmentioning

confidence: 99%

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Peptide Inhibitors of Kv1.5: An Option for the Treatment of Atrial Fibrillation

et al. 2021

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The human voltage gated potassium channel Kv1.5 that conducts the IKur current is a key determinant of the atrial action potential. Its mutations have been linked to hereditary forms of atrial fibrillation (AF), and the channel is an attractive target for the management of AF. The development of IKur blockers to treat AF resulted in small molecule Kv1.5 inhibitors. The selectivity of the blocker for the target channel plays an important role in the potential therapeutic application of the drug candidate: the higher the selectivity, the lower the risk of side effects. In this respect, small molecule inhibitors of Kv1.5 are compromised due to their limited selectivity. A wide range of peptide toxins from venomous animals are targeting ion channels, including mammalian channels. These peptides usually have a much larger interacting surface with the ion channel compared to small molecule inhibitors and thus, generally confer higher selectivity to the peptide blockers. We found two peptides in the literature, which inhibited IKur: Ts6 and Osu1. Their affinity and selectivity for Kv1.5 can be improved by rational drug design in which their amino acid sequences could be modified in a targeted way guided by in silico docking experiments.

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Section: Gating Modifiers Peptidesmentioning

confidence: 99%

“…For Kv channels, the selectivity of these toxins becomes a little tighter since all of these peptides affect mainly Kv2 and/or Kv4 subfamilies [66]. Although, peptides as the GiTx1 [79] and JZTX-1 [82] have shown an effect on hERG channels.…”

Section: Gating Modifiers Peptidesmentioning

confidence: 99%