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dc.contributor.authorNirthanan, Selvanayagamen_US
dc.contributor.authorPil, Joosten_US
dc.contributor.authorAbdel-Mottaleb, Yousraen_US
dc.contributor.authorSugahara, Yukoen_US
dc.contributor.authorGopalakrishnakone, Ponnampalamen_US
dc.contributor.authorS. Joseph, Jeremiahen_US
dc.contributor.authorSato, Kazukien_US
dc.contributor.authorTytgat, Janen_US
dc.date.accessioned2017-05-03T15:29:01Z
dc.date.available2017-05-03T15:29:01Z
dc.date.issued2005en_US
dc.date.modified2009-12-18T06:34:09Z
dc.identifier.issn00062952en_US
dc.identifier.doi10.1016/j.bcp.2004.10.018en_AU
dc.identifier.urihttp://hdl.handle.net/10072/27780
dc.description.abstractA new family of weak K+ channel toxins (designated ?-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), ?-hefutoxin-1 (?-KTx1.1) was investigated and found to block Kv 1.2 (IC50 ~40 卩 and Kv 1.3 (IC50 ~150 卩 channels. In the present study, ?-KTx1.3, that shares ~60% identity with ?-hefutoxin 1, has been isolated from Heterometrus spinifer venom. Interestingly, despite the presence of the functional dyad (Y5 and K19), ?-KTx1.3 failed to reproduce the K+ channel blocking activity of ?-hefutoxin-1. Since the dyad lysine in ?-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 ?-KTx1.3, substituting K20 with a neutral (K20A) or a negatively (K20E) or another positively (K20R) charged amino acid were synthesized. ?-KTx1.3 K20E, in congruence with ?-hefutoxin 1 with respect to subtype selectivity and affinity, produced blockade of Kv 1.2 (IC50 = 36.8 ᠴ.9 卩 and Kv 1.3 (IC50 = 53.7 ᠶ.7 卩 but not Kv 1.1 channels. ?-KTx1.3 K20A produced blockade of both Kv 1.2 (IC50 = 36.9 ᠴ.9 卩 and Kv 1.3 (IC50 = 115.7 ᠷ.3 卩 and in addition, acquired affinity for Kv 1.1 channels (IC50 = 110.7 ᠷ.7 卩. ?-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 ?-KTx1.3.en_US
dc.description.peerreviewedYesen_US
dc.description.publicationstatusYesen_AU
dc.languageEnglishen_US
dc.language.isoen_AU
dc.publisherElsevier Incen_US
dc.publisher.placeNew York, NYen_US
dc.publisher.urihttp://www.elsevier.com/wps/find/journaldescription.cws_home/525454/description#descriptionen_AU
dc.relation.ispartofstudentpublicationNen_AU
dc.relation.ispartofpagefrom669en_US
dc.relation.ispartofpageto678en_US
dc.relation.ispartofissue4en_US
dc.relation.ispartofjournalBiochemical Pharmacologyen_US
dc.relation.ispartofvolume69en_US
dc.rights.retentionYen_AU
dc.subject.fieldofresearchReceptors and Membrane Biologyen_US
dc.subject.fieldofresearchBasic Pharmacologyen_US
dc.subject.fieldofresearchcode060110en_US
dc.subject.fieldofresearchcode111501en_US
dc.titleAssignment of voltage-gated potassium channel blocking activity to κ-KTx1.3, a non-toxic homologue of κ-hefutoxin-1, from Heterometrus spinifer venomen_US
dc.typeJournal articleen_US
dc.type.descriptionC1 - Peer Reviewed (HERDC)en_US
dc.type.codeC - Journal Articlesen_US
gro.date.issued2005
gro.hasfulltextNo Full Text


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