TAILIEUCHUNG - Báo cáo Y học: A chimeric scorpion a-toxin displays de novo electrophysiological properties similar to those of a-like toxins

Laboratoire des Venins et Toxines, Institut Pasteur de Tunis, Tunisia; 2De´partement d’Inge´nierie et d’Etude des Prote´ines, CEA, Saclay, France; 3UMR 6560, Universite´ de la Me´diterrane´e, CNRS, Inge´nierie des Prote´ines, Laboratoire de Biochimie, IFR Jean-Roche, Faculte´ de Me´decine Nord, Marseille, France; 4Laboratoire de Neurophysiologie UPRES EA 2647, UFR Sciences, Angers, France BotXIV and LqhaIT are two structurally related long chain scorpion a-toxins that inhibit sodium current inactivation in excitable cells. However, while LqhaIT from Leiurus quinquestriatus hebraeus is classified as a true and strong insect a-toxin, BotXIV from Buthus occitanus tunetanus is characterized by moderate biological activities | Eur. J. Biochem. 269 2831-2841 2002 FEBS 2002 doi A chimeric scorpion a-toxin displays de novo electrophysiological properties similar to those of a-like toxins Balkiss Bouhaouala-Zahar1. Rvm Benkhalifa1. Najet Srairi1. Ilhem Zenouaki1. Caroline Lianv-Lemaire2 Pascal Drevet2 Francois Samnieri3 Marcel Pelhate4 Mohamed El Aveb1 Andre Menez2. Habib Karoui1 and Frederic Ducancel2 1 Laboratoire des Venins et Toxines Institut Pasteur de Tunis Tunisia 2Dèpartement dTngénierie et d Etude des Proteines CEA Saclay France 2UMR 6560 Universite de la Mediterranee CNRS Ingenierie des Proteines Laboratoire de Biochimie IFR Jean-Roche Faculte de Medecine Nord Marseille France 4Laboratoire de Neurophysiologie UPRES EA 2647 UFR Sciences Angers France BotXIV and LqhaIT are two structurally related long chain scorpion a-toxins that inhibit sodium cLI rrent inactivation in excitable cells. However while LqhalT from Leiurus quinquestriatus hebraeus is classified as a true and strong insect a-toxin BotXIV from Buthus occitanus tunetanus is characterized by moderate biological activities. To assess the possibility that structural differences between these two molecules could reflect the localization of particular functional topographies we compared their sequences. Three structurally deviating segments located in three distinct and exposed loops were identified. They correspond to residues 8-10 19-22 and 38-43. To evaluate their functional role three BotXIV LqhalT chimeras were designed by transferring the corresponding LqhaIT sequences into BotXIV. Structural and antigenic characterizations of the resulting recombinant chimera show that BotXIV can accommodate the imposed modifications confirming the structural flexibility of that particular a b fold. Interestingly substitution of residues 8-10 yields to a new electrophysiological profile of the corresponding variant partially comparable to that one of a-like scorpion toxins. Taken together these results .

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