Elucidation of the solution structure of cardiotoxin analogue V from the Taiwan cobra (Naja naja atra) - Identification of structural features important for the lethal action of snake venom cardiotoxins
G. Jayaraman et al., Elucidation of the solution structure of cardiotoxin analogue V from the Taiwan cobra (Naja naja atra) - Identification of structural features important for the lethal action of snake venom cardiotoxins, PROTEIN SCI, 9(4), 2000, pp. 637-646
The aim of the present study is to understand the structural features respo
nsible for the lethal activity of snake venom cardiotoxins. Comparison of t
he lethal potency of the five cardiotoxin isoforms isolated from the venom
of Taiwan cobra (Naja naja atra) reveals that the lethal potency of CTX I a
nd CTX V are about twice of that exhibited by CTX II, CTX III, and CTX IV.
In the present study, the solution structure of CTX V has been determined a
t high resolution using multidimensional proton NMR spectroscopy and dynami
cal simulated annealing techniques. Comparison of the high resolution solut
ion structures of CTX V with that of CTX IV reveals that the secondary stru
ctural elements in both the toxin isoforms consist of a triple and double-s
tranded antiparallel beta-sheet domains. Critical examination of the three-
dimensional structure of CTX V shows that the residues at the tip of Loop I
II form a distinct "finger-shaped" projection comprising of nonpolar residu
es. The occurrence of the nonpolar "finger-shaped" projection leads to the
formation of a prominent cleft between the residues located at the tip of L
oops II and III. Interestingly, the occurrence of a backbone hydrogen bondi
ng (Va127CO to Leu48NH) in CTX IV is found to distort the "finger-shaped" p
rojection and consequently diminish the cleft formation at the tip of Loops
II and III. Comparison of the solution structures and lethal potencies of
other cardiotoxin isoforms isolated from the Taiwan cobra (Naja naja atra)
venom shows that a strong correlation exists between the lethal potency and
occurrence of the nonpolar "finger-shaped" projection at the tip of Loop I
II. Critical analysis of the structures of the various CTX isoforms from th
e Taiwan cobra suggest that the degree of exposure of the cationic charge (
to the solvent) contributed by the invariant lysine residue at position 44
on the convex side of the CTX molecules could be another crucial factor gov
erning their lethal potency.