• myGriffith
    • Staff portal
    • Contact Us⌄
      • Future student enquiries 1800 677 728
      • Current student enquiries 1800 154 055
      • International enquiries +61 7 3735 6425
      • General enquiries 07 3735 7111
      • Online enquiries
      • Staff phonebook
    View Item 
    •   Home
    • Griffith Research Online
    • Journal articles
    • View Item
    • Home
    • Griffith Research Online
    • Journal articles
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

  • All of Griffith Research Online
    • Communities & Collections
    • Authors
    • By Issue Date
    • Titles
  • This Collection
    • Authors
    • By Issue Date
    • Titles
  • Statistics

  • Most Popular Items
  • Statistics by Country
  • Most Popular Authors
  • Support

  • Contact us
  • FAQs
  • Admin login

  • Login
  • Assignment of voltage-gated potassium channel blocking activity to κ-KTx1.3, a non-toxic homologue of κ-hefutoxin-1, from Heterometrus spinifer venom

    Author(s)
    Nirthanan, S
    Pil, J
    Abdel-Mottaleb, Y
    Sugahara, Y
    Gopalakrishnakone, P
    Joseph, JS
    Sato, K
    Tytgat, J
    Griffith University Author(s)
    Nirthanan, Niru
    Year published
    2005
    Metadata
    Show full item record
    Abstract
    A new family of weak K+ channel toxins (designated κ-KTx) with a novel "bi-helical" scaffold has recently been characterized from Heterometrus fulvipes (Scorpionidae) venom. Based on the presence of the minimum functional dyad (Y5 and K19), κ-hefutoxin-1 (κ-KTx1.1) was investigated and found to block Kv 1.2 (IC50 ~40 μM and Kv 1.3 (IC50 ~150 μM channels. In the present study, κ-KTx1.3, that shares ~60% identity with κ-hefutoxin 1, has been isolated from Heterometrus spinifer venom. Interestingly, despite the presence of the functional dyad (Y5 and K19), κ-KTx1.3 failed to reproduce the K+ channel blocking activity of ...
    View more >
    A new family of weak K+ channel toxins (designated κ-KTx) with a novel "bi-helical" scaffold has recently been characterized from Heterometrus fulvipes (Scorpionidae) venom. Based on the presence of the minimum functional dyad (Y5 and K19), κ-hefutoxin-1 (κ-KTx1.1) was investigated and found to block Kv 1.2 (IC50 ~40 μM and Kv 1.3 (IC50 ~150 μM channels. In the present study, κ-KTx1.3, that shares ~60% identity with κ-hefutoxin 1, has been isolated from Heterometrus spinifer venom. Interestingly, despite the presence of the functional dyad (Y5 and K19), κ-KTx1.3 failed to reproduce the K+ channel blocking activity of κ-hefutoxin-1. Since the dyad lysine in κ-KTx1.3 was flanked by another lysine (K20), it was hypothesized that this additional positive charge could hinder the critical electrostatic interactions known to occur between the dyad lysine and the Kv 1 channel selectivity filter. Hence, mutants of κ-KTx1.3, substituting K20 with a neutral (K20A) or a negatively (K20E) or another positively (K20R) charged amino acid were synthesized. κ-KTx1.3 K20E, in congruence with κ-hefutoxin 1 with respect to subtype selectivity and affinity, produced blockade of Kv 1.2 (IC50 = 36.8 ᠴ 4.9 μM and Kv 1.3 (IC50 = 53.7 ᠶ.6.7 μM but not Kv 1.1 channels. κ-KTx1.3 K20A produced blockade of both Kv 1.2 (IC50 = 36.9 ᠴ.4.9 μM and Kv 1.3 (IC50 = 115.7 ᠷ.7.3 μM and in addition, acquired affinity for Kv 1.1 channels (IC50 = 110.7 ᠷ.7.7 μM . κ-KTx1.3 K20R failed to produce any blockade on the channel subtypes tested. These data suggest that the presence of an additional charged residue in a position adjacent to the dyad lysine impedes the functional block of Kv 1 channels produced by κ-KTx1.3.
    View less >
    Journal Title
    Biochemical Pharmacology
    Volume
    69
    Issue
    4
    Publisher URI
    http://www.elsevier.com/wps/find/journaldescription.cws_home/525454/description#description
    DOI
    https://doi.org/10.1016/j.bcp.2004.10.018
    Subject
    Biochemistry and cell biology
    Receptors and membrane biology
    Pharmacology and pharmaceutical sciences
    Basic pharmacology
    Publication URI
    http://hdl.handle.net/10072/27780
    Collection
    • Journal articles

    Footer

    Disclaimer

    • Privacy policy
    • Copyright matters
    • CRICOS Provider - 00233E
    • TEQSA: PRV12076

    Tagline

    • Gold Coast
    • Logan
    • Brisbane - Queensland, Australia
    First Peoples of Australia
    • Aboriginal
    • Torres Strait Islander