The structural and functional contribution of N-terminal region and His-47 on Taiwan cobra phospholipase A2

Modification of His-47 and removal of the N-terminal octapeptide caused a different effect on the structure of Naja naja atra (Taiwan cobra) phospholipase A₂ (PLA₂). Unlike native enzyme, Ca²⁺ induced an alteration in the structural flexibility of His-modified PLA₂. Moreover, the spatial positions of Trp residues in His-modified PLA₂ were not properly rearranged toward lipid-water interface in the presence of Ca²⁺. CD spectra and fluorescence measurement showed that the dynamic properties of Trp residues and the gross conformation of N-terminally truncated PLA₂ were totally different from native enzyme. Although a precipitous drop in the enzymatic activity was observed with modified PLA₂. His-modified PLA₂ and N-terminally truncated PLA₂ retained cytotoxicity on inducing necrotic death of human neuroblastoma. SK-N-SH cells. Our data suggest that structural perturbations elicited by the chemical modification cause a dissociation of enzymatic activity and cytotoxicity of PLA₂.