Cardiotoxin II from Taiwan cobra venom, Naja naja atra. Structure in solution and comparison among homologous cardiotoxins.

The three-dimensional structure in solution of cardiotoxin 11, a membrane toxin from the venom of Taiwan cobra, Naja nqja atra, was determined using 'H nuclear magnetic resonance spectroscopy and molecular modeling based on the hybrid distance geometryldynamic simulated annealing technique.A complete sequencespecific proton assignment was obtained, and the secondary structures of the protein were determined from information on nuclear Overhauser effect connectivities, coupling constants, and hydrogen exchange were confirmed using the main-chain-directed strategy.Twelve simulated annealing structures found to be within a single family were selected based on the condition of distance constraint violation less than 0.02 nm and the dihedral angle violation less than 4".The average atomic root mean square deviation between 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 nm and 0.117 nm, respectively, when considering the secondary structural 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 p sheets.Comparisons are made between this structure and those of its homologous cardiotoxins in order to derive further information on their structural variations.Toxins from Elapidae venom constitute homologous proteins in a large family.Despite their sequence homologies, there are pronounced distinctions in the functions of toxins of various types.They have been classified as neurotoxins (both long and short) and cardiotoxins (1-4) based on their functions.Whereas neurotoxins bind t o a protein receptor at the postsynaptic level and block acetylcholine reception, the action of cardiotoxins results in various effects, such as hemolysis, cytotoxicity, depolarization of excitable membranes, and modulation of membranal enzyme activity (5-8).However, there exist variations in the activity of cardiotoxins among themselves (9-11).Cardiotoxin I1 (CTX 11)' is a membrane protein isolated from Taiwan cobra, N. nuja utru (12).I t consists of 60 amino acid NSC 83-0208-"007-115 from the National Science Council of the Re-* This work was supported by Grants NSC 83-0203-B-007-22 and public of China. The atomic coordinates (code 1CAR) have been deposited in the ProteinData Bank, Brookhaven National Laboratory, Upton, IVY The costs of charges.This article must therefore be hereby marked "advertisement" publication of this article were defrayed in part by the payment of page in accordance with 18 U.S.C.Section 1734 solely to indicate this fact.