tailieunhanh - Báo cáo khoa học: NMR solution structure of Cn12, a novel peptide from the Mexican scorpion Centruroides noxius with a typical b-toxin sequence but with a-like physiological activity

Cn12 isolated from the venom of the scorpionCentruroides noxiushas 67 amino-acid residues, closely packed with four disulfide primary structure and disulfide bridges were is not lethal to mammals and arthropodsin vivoat doses up to 100lgper structure was determined by proton NMR using 850 dis-tance constraints, 36 /angles derived from 36 coupling constants obtained by two different methods, and 22 hydrogen overall structure has a two and half turn a-helix (residues 24–32), three strands of antiparallel b-sheet (residues 2–4, 37–40 and 45–48), and a type II turn (residues 41–44) | Eur. J. Biochem. 271 2504-2516 2004 FEBS 2004 doi NMR solution structure of Cn12 a novel peptide from the Mexican scorpion Centruroidesnoxius with a typical p-toxin sequence but with a-like physiological activity Federico del Rio-Portilla1 Elizabeth Hernandez-Marin1 Genaro Pimienta2 Fredy V. Coronas2 Fernando Z. Zamudio2 Ricardo C. Rodríguez de la Vega2 Enzo Wanke2 3 and Lourival D. Possani2 1 Institute of Chemistry National Autonomous University of Mexico Mexico City Mexico 2Department of Molecular Medicine and Bioprocesses Institute of Biotechnology National Autonomous University of Mexico 3Dipartimento di Biotecnologie e Bioscienze Universita di Milano-Bicocca Milan Italy Cn12 isolated from the venom of the scorpion Centruroides noxius has 67 amino-acid residues closely packed with four disulfide bridges. Iss primary tlruclure and disulfide bridges were determined. C11I2 is not lethal to mammals add arthropods in vivo at doses up to 100 Ig per animal. Its 3D structure was determined by proton NMR using 850 distance constraints 36 angles derived from 36 coupling constants obtained by two different methods and 22 hydrogen bonds. The ovrrall ttuicfirrc has a two and half turn a-helix residues 24-32 three strands of antiparallel b-sheet residues 2-4 37-40 and 45-48 and a type II turn residues 41-44 . The amino-acíd eeqLienee of Cnl2 nse m-bles the b scorpion toxin class although patch-clamp experiments showed the induction of supplementary slow inactivation of Na channels in F-11 cells mouse neuroblastoma N18TG-2 X rat DRG2 which means that it behaves more like an a scorpion toxin. Tito dehaviuur prompted us to analyse Na channel binding sites using information from 112 Na channel gene clones available in the literature focusing on the extracytoplasmic loops of the S5-S6 transmembrane segments of domain I and the S3-S4 segments of domain IV sites considered to be responsible for binding a scorpion toxins. Keywords Centruroides noxius