ACP-TX-I and ACP-TX-II, Two Novel Phospholipases A₂ Isolated from Trans-Pecos Copperhead Agkistrodon contortrix...

This work reports the purification and biochemical and functional characterization of ACP-TX-I and ACP-TX-II, two phospholipases A₂ (PLA₂) from Agkistrodon contortrix pictigaster venom. Both PLA₂s were highly purified by a single chromatographic step on a C₁₈ reverse phase HPLC column. Various peptide sequences from these two toxins showed similarity to those of other PLA₂ toxins from viperid snake venoms. ACP-TX-I belongs to the catalytically inactive K49 PLA₂ class, while ACP-TX-II is a D49 PLA₂, and is enzymatically active. ACP-TX-I PLA₂ is monomeric, which results in markedly diminished myotoxic and inflammatory activities when compared with dimeric K49 PLA₂s, confirming the hypothesis that dimeric structure contributes heavily to the profound myotoxicity of the most active viperid K49 PLA₂s. 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 PLA₂ is cytotoxic to A549 lung carcinoma cells, indicating that cytotoxicity to these tumor cells does not require enzymatic activity.