CARDIOTOXIN-II FROM TAIWAN COBRA VENOM, NAJA-NAJA-ATRA - STRUCTURE INSOLUTION AND COMPARISON AMONG HOMOLOGOUS CARDIOTOXINS

The three-dimensional structure in solution of cardiotoxin II, a membr ane toxin from the venom of Taiwan cobra, Naja naja atra, was determin ed using H-1 nuclear magnetic resonance spectroscopy and molecular mod eling based on the hybrid distance geometry/dynamic simulated annealin g technique. A complete sequence-specific proton assignment was obtain ed, and the secondary structures of the protein were determined from i nformation on nuclear Overhauser effect connectivities, coupling const ants, and hydrogen exchange were confirmed using the main-chain-direct ed strategy. Twelve simulated annealing structures found to be within a single family were selected based on the condition of distance const raint violation less than 0.02 nm and the dihedral angle violation les s than 4 degrees. The average atomic root mean square deviation betwee n the selected structures and their geometric average are 0.079 nm for the backbone atoms and 0.137 nm for all heavy atoms; they are 0.044 n m and 0.117 nm, respectively, when considering the secondary structura l residues only. The molecule adopts a compact structure consisting of three major loops emerging from a globular head. These loops contain five strands to form double- and a triple-stranded antiparallel beta s heets. Comparisons are made between this structure and those of its ho mologous cardiotoxins in order to derive further information on their structural variations.