Cardiotoxin III

A CASE STUDY OF CARDIOTOXIN III FROM THE TAIWAN COBRA (Naja naja atm)... 

The Taiwan cobra (Naja naja atm) is a rich source for the cardiotoxins (37). To date six isoforms have been isolated from this source (38). The isoforms are numbered on column chromatographic profiles (39). Of the six isoforms, cardiotoxin III (CTX III) is the major fraction. It constitutes 50 - 60% of the total dry weight of the cardiotoxin isoforms and hence the best characterized (of the toxin isoforms) from this source (Naja naja atm) (40). 

A Case Study of Cardiotoxin III from the Taiwan Cobra... 

Two dimensional Nuclear Magnetic Resonance (2D NMR) technique is facile and offers an easy handle to tackle problems involving structural elucidation of proteins in solution (55). Recently, we successfully employed this technique to study the solution structure (8,32,56) and protein folding (57) aspects of Cardiotoxin III from the Taiwan cobra. 

Bhaskaran, R.,Huang, C.C., Chang, D.K., and Yu, C., 1994, Cardiotoxin III from the Taiwan cobra Naja naja atrd) Determination of structure in solution and comparison with short neurotoxins, J. Mol. Biol. 235, 1291-1301. 

Figure 8. ESI-mass spectrum of snake venom polypeptides (A, acquired spectrum B, deconvoluted spectrum I, Naja Naja atra a-toxin II, Naja Naja atra cardiotoxin III, Erabutoxin A IV, Erabutoxin B).

Fasciculins belong to the structural family of threefingered toxins from Elapidae snake venoms, which include the a-neurotoxins that block the nAChR and the cardiotoxins that interact with cell membranes. The features unique to the known primary and tertiary structures of the fasciculin molecule were analyzed by Flarald et al. (1995). Loop I contains an arginine at position 11, which is found only in the fasciculins and could form a pivotal anchoring point to AChE. Loop II contains five cationic residues near its tip, which are partly charge-compensated by anionic side chains in loop III. 

The Far UV CD spectrum (secondary structure region) of CTX III at different pH conditions shows that the 215 nm (an indicator of the p -sheet content) band is maximum at pH 6.0. The intensity of this Cotton band decreases as the pH of the solvent is either increased or decreased from pH 6.0. This finding raises an interesting question as to whether the NMR solution structures of cardiotoxins are stringently dependent on the pH of the solvent. Though we have not carried out systematic study, we feel that such a possibility evidently exists. Infact, differences in the NMR solution structures of a-cobratoxin (a neurotoxin) solved under different pH conditions is reported (82). We presume that subtle variations of this sort (in the structure) could explain the battery of drastically different biological activities reported for the same cardiotoxin molecule under different conditions. 

In this chapter, only a case study of CTX III from the Taiwan cobra is presented. However, we believe that the lesson learnt herein, are generally applicable to all snake venom cardiotoxins. Though a lot of useful information is now available on CTX III and cardiotox-... 

Takechi, M., Tanaka, Y., and Hayashi, K., 1986, Binding of cardiotoxin analogue III from Formosan cobra to FL cells Le, FEES Lett. 205 143-146. 

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