{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T06:33:58Z","timestamp":1789454038394,"version":"build-2803163510"},"reference-count":40,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2003,5,30]],"date-time":"2003-05-30T00:00:00Z","timestamp":1054252800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Proteins"],"published-print":{"date-parts":[[2003,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>To gain insight into the molecular determinants that define the specificity of interaction of pore\u2010blocking peptides, such as agitoxin 2 (AgTX2), charybdotoxin (ChTX), and iberiotoxin (IbTX) with the <jats:italic>Shaker<\/jats:italic>\u2010type voltage\u2010gated potassium channel Kv1.3, or the large\u2010conductance Ca<jats:sup>2+<\/jats:sup>\u2010activated K<jats:sup>+<\/jats:sup> (Maxi\u2010K) channel, homology models of these channels were generated based on the crystal structure of the bacterial, KcsA, potassium channel. Peptide\u2013channel complexes were analyzed to evaluate the predicted interaction interfaces between the peptides and the channels' outer vestibules. The docking model, for either AgTX2 or ChTX with the Kv1.3 channel, predicts a novel hydrogen bonding interaction between the Asn30 side\u2010chain of the peptide and the Asp381 side\u2010chain of the channel. This interaction is consistent with the &gt;500\u2010fold decreased potency of both AgTX2 and ChTX mutants at position 30 for the <jats:italic>Shaker<\/jats:italic> channel [(Ranganathan et al., <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"#bib11\">Neuron 1996;16:131\u2013139)<\/jats:ext-link>; (Goldstein et al., <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"#bib14\">Neuron 1994;12:1377\u20131388<\/jats:ext-link>)]. This hydrogen bonding interaction also suggests that Gly30 in IbTX may be the critical determinant for its lack of activity against <jats:italic>Shaker<\/jats:italic> Kv channels. The model of the Maxi\u2010K channel reveals a narrower and more structurally restrained outer vestibule in which the aromatic residues Phe266 and Tyr294 may stabilize binding of IbTX and ChTX by \u03c0\u2013\u03c0 stacking with the aromatic residues Trp14 and Tyr36 of the peptides. This study also suggests that the extra net negative charge of IbTX is not related to the selectivity of this peptide for the Maxi\u2010K channel. Proteins 2003;52:146\u2013154. \u00a9 2003 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/prot.10341","type":"journal-article","created":{"date-parts":[[2003,6,24]],"date-time":"2003-06-24T10:16:06Z","timestamp":1056449766000},"page":"146-154","source":"Crossref","is-referenced-by-count":64,"title":["Interaction of agitoxin2, charybdotoxin, and iberiotoxin with potassium channels: Selectivity between voltage\u2010gated and Maxi\u2010K channels"],"prefix":"10.1002","volume":"52","author":[{"given":"Ying\u2010Duo","family":"Gao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria L.","family":"Garcia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2003,5,30]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.2476850"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/350232a0"},{"key":"e_1_2_7_4_2","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1016\/S0021-9258(17)42402-1","article-title":"Purification and reconstitution of the high\u2010conductance calcium\u2010activated potassium channel from tracheal smooth muscle","volume":"269","author":"Garcia\u2010Calvo M","year":"1994","journal-title":"J Biol 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