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X-ray diffraction and nuclear magnetic resonance (NMR) spectroscopy were done to characterize the structure of the cardiotoxin V from Taiwan cobra (CTX A5), a P-type CTX. The results showed that CTX A5 exhibits a dimeric assembly at pH 8.5. There were, however, differences in the data obtained from the two analytical methods which are localized at two functionally important regions in loops I and II. Such disparities were attributed to the difference in the protonation state of His4 at different pH which results to a reorientation of the His4 imidazole ring and to the hydrophobic contact between CTX dimers in the crystal packing as well as to the interaction of water molecules with amino acid residues in the loop II region.

Acidic pH disturbs the structural stability of the cardiotoxin V from the venom of the cobra Naja naja atra (CTX A5), leading to suppression of membrane-associated activity of the molecule. However, it fails to alter the overall beta-sheet of the molecule. The structural stability changes in CTX A5 occur at pH2 and pH4. The amino acid residue in the molecule, Glu-17, is involved in its structural stability. This residue disturbs the interaction between two other residues, Lys-2 and Asp-59, thus disturbing the overall stability of the beta-sheet in the presence of a denaturing reagent.

Cardiotoxin V from Naja naja atra (CTX A5) shows pH-dependence while binding to phosphatidylcholine membrane with pK(sub a) value around 6.0. Proton NMR analysis indicates less CTX A5 relation to membranes at low pH, due to protonation of His-4 near the CTX loop I region's membrane binding site. Due to the influence of pH on pK(sub a), the protonation of His-4 residue also leads to local conformational change in the loop I region, and other amino acid residues in the protein's structural core receive this effect.