{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T12:08:27Z","timestamp":1763467707855},"reference-count":38,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2005,6,21]],"date-time":"2005-06-21T00:00:00Z","timestamp":1119312000000},"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":[[2005,8,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Scorpion toxins interact with their target ion channels through multiple molecular contacts. Because a \u201cgain of function\u201d approach has never been described to evaluate the importance of the molecular contacts in defining toxin affinity, we experimentally examined whether increasing the molecular contacts between a toxin and an ion channel directly impacts toxin affinity. For this purpose, we focused on two scorpion peptides, the well\u2010characterized maurotoxin with its variant Pi1\u2010like disulfide bridging (MTX<jats:sub>Pi1<\/jats:sub>), used as a molecular template, and butantoxin (BuTX), used as an N\u2010terminal domain provider. BuTX is found to be 60\u2010fold less potent than MTX<jats:sub>Pi1<\/jats:sub> in blocking Kv1.2 (IC<jats:sub>50<\/jats:sub> values of 165 nM for BuTX versus 2.8 nM for MTX<jats:sub>Pi1<\/jats:sub>). Removal of its N\u2010terminal domain (nine residues) further decreases BuTX affinity for Kv1.2 by 5.6\u2010fold, which is in agreement with docking simulation data showing the importance of this domain in BuTX\u2010Kv1.2 interaction. Transfer of the BuTX N\u2010terminal domain to MTX<jats:sub>Pi1<\/jats:sub> results in a chimera with five disulfide bridges (BuTX\u2010MTX<jats:sub>Pi1<\/jats:sub>) that exhibits 22\u2010fold greater affinity for Kv1.2 than MTX<jats:sub>Pi1<\/jats:sub> itself, in spite of the lower affinity of BuTX as compared to MTX<jats:sub>Pi1<\/jats:sub>. Docking experiments performed with the 3\u2010D structure of BuTX\u2010MTX<jats:sub>Pi1<\/jats:sub> in solution, as solved by <jats:sup>1<\/jats:sup>H\u2010NMR, reveal that the N\u2010terminal domain of BuTX participates in the increased affinity for Kv1.2 through additional molecular contacts. Altogether, the data indicate that acting on molecular contacts between a toxin and a channel is an efficient strategy to modulate toxin affinity. Proteins 2005. \u00a9 2005 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/prot.20509","type":"journal-article","created":{"date-parts":[[2005,6,21]],"date-time":"2005-06-21T16:52:48Z","timestamp":1119372768000},"page":"401-411","source":"Crossref","is-referenced-by-count":10,"title":["Increasing the molecular contacts between maurotoxin and Kv1.2 channel augments ligand 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