{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T21:31:04Z","timestamp":1780349464821,"version":"3.54.1"},"reference-count":0,"publisher":"Portland Press Ltd.","issue":"1","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2004,1,1]]},"abstract":"<jats:p>CoTX1 (cobatoxin 1) is a 32-residue toxin with three disulphide bridges that has been isolated from the venom of the Mexican scorpion Centruroides noxius Hoffmann. Here we report the chemical synthesis, disulphide bridge organization, 3-D (three-dimensional) solution structure determination, pharmacology on K+ channel subtypes (voltage-gated and Ca2+-activated) and docking-simulation experiments. An enzyme-based cleavage of the synthetic folded\/oxidized CoTX1 indicated half-cystine pairs between Cys3-Cys22, Cys8-Cys27 and Cys12-Cys29. The 3-D structure of CoTX1 (solved by 1H-NMR) showed that it folds according to the common \u03b1\/\u03b2 scaffold of scorpion toxins. In vivo, CoTX1 was lethal after intracerebroventricular injection to mice (LD50 value of 0.5 \u00b5g\/mouse). In vitro, CoTX1 tested on cells expressing various voltage-gated or Ca2+-activated (IKCa1) K+ channels showed potent inhibition of currents from rat Kv1.2 (Kd value of 27 nM). CoTX1 also weakly competed with 125I-labelled apamin for binding to SKCa channels (small-conductance Ca2+-activated K+ channels) on rat brain synaptosomes (IC50 value of 7.2 \u00b5M). The 3-D structure of CoTX1 was used in docking experiments which suggests a key role of Arg6 or Lys10, Arg14, Arg18, Lys21 (dyad), Ile23, Asn24, Lys28 and Tyr30 (dyad) residues of CoTX1 in its interaction with the rat Kv1.2 channel. In addition, a [Pro7,Gln9]-CoTX1 analogue (ACoTX1) was synthesized. The two residue replacements were selected aiming to restore the RPCQ motif in order to increase peptide affinity towards SKCa channels, and to alter the CoTX1 dipole moment such that it is expected to decrease peptide activity on Kv channels. Unexpectedly, ACoTX1 exhibited an activity similar to that of CoTX1 towards SKCa channels, while it was markedly more potent on IKCa1 and several voltage-gated K+ channels.<\/jats:p>","DOI":"10.1042\/bj20030977","type":"journal-article","created":{"date-parts":[[2004,1,13]],"date-time":"2004-01-13T09:02:27Z","timestamp":1073984547000},"page":"37-49","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Cobatoxin 1 from Centruroides noxius scorpion venom: chemical synthesis, three-dimensional structure in solution, pharmacology and docking on K+ channels"],"prefix":"10.1042","volume":"377","author":[{"given":"Besma","family":"JOUIROU","sequence":"first","affiliation":[{"name":"Laboratoire International Associ\u00e9 d'Ing\u00e9nierie Biomol\u00e9culaire, CNRS UMR 6560, Bd Pierre Dramard, 13916 Marseille Cedex 20, France"},{"name":"Laboratoire des Venins et Toxines, Institut Pasteur de Tunis, Tunis-Belv\u00e9d\u00e8re, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amor","family":"MOSBAH","sequence":"additional","affiliation":[{"name":"Laboratoire International Associ\u00e9 d'Ing\u00e9nierie Biomol\u00e9culaire, CNRS UMR 6560, Bd Pierre Dramard, 13916 Marseille Cedex 20, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Violeta","family":"VISAN","sequence":"additional","affiliation":[{"name":"Universit\u00e4t Ulm, Albert Einstein-Allee 11, D-89081 Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"GRISSMER","sequence":"additional","affiliation":[{"name":"Universit\u00e4t Ulm, Albert Einstein-Allee 11, D-89081 Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarrah","family":"M'BAREK","sequence":"additional","affiliation":[{"name":"Laboratoire International Associ\u00e9 d'Ing\u00e9nierie Biomol\u00e9culaire, CNRS UMR 6560, Bd Pierre Dramard, 13916 Marseille Cedex 20, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziad","family":"FAJLOUN","sequence":"additional","affiliation":[{"name":"Laboratoire International Associ\u00e9 d'Ing\u00e9nierie Biomol\u00e9culaire, CNRS UMR 6560, Bd Pierre Dramard, 13916 Marseille Cedex 20, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jurphaas","family":"VAN RIETSCHOTEN","sequence":"additional","affiliation":[{"name":"Laboratoire International Associ\u00e9 d'Ing\u00e9nierie Biomol\u00e9culaire, CNRS UMR 6560, Bd Pierre Dramard, 13916 Marseille Cedex 20, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christiane","family":"DEVAUX","sequence":"additional","affiliation":[{"name":"Laboratoire International Associ\u00e9 d'Ing\u00e9nierie Biomol\u00e9culaire, CNRS UMR 6560, Bd Pierre Dramard, 13916 Marseille Cedex 20, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herv\u00e9","family":"ROCHAT","sequence":"additional","affiliation":[{"name":"Laboratoire International Associ\u00e9 d'Ing\u00e9nierie Biomol\u00e9culaire, CNRS UMR 6560, Bd Pierre Dramard, 13916 Marseille Cedex 20, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guy","family":"LIPPENS","sequence":"additional","affiliation":[{"name":"CNRS UMR 8525, Institut Pasteur de Lille, 1 rue du Professeur Calmette BP447, 59021, Lille Cedex, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed EL","family":"AYEB","sequence":"additional","affiliation":[{"name":"Laboratoire International Associ\u00e9 d'Ing\u00e9nierie Biomol\u00e9culaire, CNRS UMR 6560, Bd Pierre Dramard, 13916 Marseille Cedex 20, France"},{"name":"Laboratoire des Venins et Toxines, Institut Pasteur de Tunis, Tunis-Belv\u00e9d\u00e8re, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel","family":"DE WAARD","sequence":"additional","affiliation":[{"name":"Inserm EMI 9931, CEA, IFR 27, DRDC, Canaux Ioniques et Signalisation, 17 rue des Martyrs, 38054 Grenoble Cedex 09, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamel","family":"MABROUK","sequence":"additional","affiliation":[{"name":"Laboratoire International Associ\u00e9 d'Ing\u00e9nierie Biomol\u00e9culaire, CNRS UMR 6560, Bd Pierre Dramard, 13916 Marseille Cedex 20, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Marc","family":"SABATIER","sequence":"additional","affiliation":[{"name":"Laboratoire International Associ\u00e9 d'Ing\u00e9nierie Biomol\u00e9culaire, CNRS UMR 6560, Bd Pierre Dramard, 13916 Marseille Cedex 20, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","container-title":["Biochemical 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