ACP-TX-I and ACP-TX-II, Two Novel Phospholipases A 2 Isolated from Trans-Pecos Copperhead Agkistrodon contortrix pictigaster Venom: Biochemical and Functional Characterization.

This work reports the purification and biochemical and functional characterization of ACP-TX-I and ACP-TX-II, two phospholipases A ₂ (PLA ₂ ) from Agkistrodon contortrix pictigaster venom. Both PLA ₂ s were highly purified by a single chromatographic step on a C ₁₈ reverse phase HPLC column. Various peptide sequences from these two toxins showed similarity to those of other PLA ₂ toxins from viperid snake venoms. ACP-TX-I belongs to the catalytically inactive K49 PLA ₂ class, while ACP-TX-II is a D49 PLA ₂ , and is enzymatically active. ACP-TX-I PLA ₂ is monomeric, which results in markedly diminished myotoxic and inflammatory activities when compared with dimeric K49 PLA ₂ s, confirming the hypothesis that dimeric structure contributes heavily to the profound myotoxicity of the most active viperid K49 PLA ₂ s. ACP-TX-II exhibits the main pharmacological actions reported for this protein family, including in vivo local myotoxicity, edema-forming activity, and in vitro cytotoxicity. ACP-TX-I PLA ₂ is cytotoxic to A549 lung carcinoma cells, indicating that cytotoxicity to these tumor cells does not require enzymatic activity.