Role of lysine and tryptophan residues in the biological activity of toxin VII (Ts gamma) from the scorpion Tityus serrulatus
| Autor: | Hervé Rochat, Pascal Mansuelle, Madeleine Bourdeaux, Oussama Hassani, Sandrine Cestèle, F. Sampieri |
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| Přispěvatelé: | CNRS FRE2738 (FRE2738), Hôpital de la Timone [CHU - APHM] (TIMONE), Université Côte d'Azur, CNRS, UMR 7275, Institut de Pharmacologie Moléculaire et Cellulaire, Sophia Antipolis, Biochimie - Ingénierie des protéines, Centre National de la Recherche Scientifique (CNRS)-Université de la Méditerranée - Aix-Marseille 2, Ingénierie des protéines (IP), Université de la Méditerranée - Aix-Marseille 2-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 1999 |
| Předmět: |
Models
Molecular Circular dichroism Tityus serrulatus Stereochemistry [SDV]Life Sciences [q-bio] Lysine Molecular Sequence Data Neurotoxins Scorpion Venoms Biochemistry Mass Spectrometry Lethal Dose 50 Scorpions 03 medical and health sciences Mice Neurotoxin Animals Amino Acid Sequence Nitrobenzenes ComputingMilieux_MISCELLANEOUS 030304 developmental biology 0303 health sciences Edman degradation biology Chemistry Circular Dichroism 030302 biochemistry & molecular biology Tryptophan Brain Metalloendopeptidases Biological activity Acetylation biology.organism_classification Peptide Fragments Mice Inbred C57BL Sequence Alignment |
| Zdroj: | European Journal of Biochemistry European Journal of Biochemistry, Wiley, 1999, 260 (1), pp.76-86. ⟨10.1046/j.1432-1327.1999.00152.x⟩ European Journal of Biochemistry, 1999, 260 (1), pp.76-86. ⟨10.1046/j.1432-1327.1999.00152.x⟩ |
| ISSN: | 0014-2956 1432-1327 |
| DOI: | 10.1046/j.1432-1327.1999.00152.x⟩ |
| Popis: | Toxin VII (TsVII), also known as Ts gamma, is the most potent neurotoxin in the venom of the Brazilian scorpion Tityus serrulatus. It has been purified to homogeneity using a new fast and efficient method. Chemical modification of TsVII with the tryptophan-specific reagent o-nitrophenylsulfenyl chloride yielded three modified derivatives (residues Trp39, Trp50 and Trp54). Acetylation of TsVII mostly generated the monoacetylated Lys12 derivative. No side reactions were detected, as indicated by endoproteinase Lys-C peptide mapping, Edman degradation and electrospray mass spectrometry. Circular dichroism and fluorimetric measurements showed that none of the chemical modifications altered the overall structure of the derivatives. The acetylation of Lys12 or the sulfenylation of Trp39 or Trp54 led to a loss of both toxicity in mice and apparent binding affinity for rat brain and cockroach synaptosomal preparations. Sulfenylation of Trp50, however, moderately affected the toxicity of TsVII in mice and had almost no effect on its binding properties. A 3-dimensional model of TsVII was constructed by homology modeling. It suggests that the most reactive residues (Lys12 and Trp39 and Trp54) are all important in the functional disruption of neuronal sodium channels by TsVII, and are close to each other in the hydrophobic conserved region. |
| Databáze: | OpenAIRE |
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