The structural and functional contribution of N ‐terminal region and His‐47 on Taiwan cobra phospholipase A 2

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 A 2 (PLA 2 ). Unlike native enzyme, Ca 2+ induced an alteration in the structural flexibility of His‐modified PLA 2 . Moreover, the spatial positions of Trp residues in His‐modified PLA 2 were not properly rearranged toward lipid–water interface in the presence of Ca 2+ . CD spectra and fluorescence measurement showed that the dynamic properties of Trp residues and the gross conformation of N ‐terminally truncated PLA 2 were totally different from native enzyme. Although a precipitous drop in the enzymatic activity was observed with modified PLA 2 , His‐modified PLA 2 and N ‐terminally truncated PLA 2 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 PLA 2 . Copyright © 2007 European Peptide Society and John Wiley & Sons, Ltd.