Crystallization and preliminary X-ray diffraction analysis of a myotoxic Lys49-PLA2 from Bothrops jararacussu venom complexed with p-bromophenacyl bromide

Abstract

For the first time, a non-catalytic and myotoxic Lys49-PLA2 (BthTX-I from Bothrops jararacussu venom) has been crystallized with BPB inhibitor. X-ray diffraction data were collected and electron-density calculations showed that the ligand is bound to the His48 residue. BthTX-I with His48 chemically modified by BPB shows strongly reduced myotoxic and cytotoxic activities. This suggests a biological correlation between the modification of His48, which is associated with catalytic activity of PLA2s, and other toxicological activities of Lys49-PLA2s.

Figure 1

Crystals of the BthTX-I–BPB complex.

Figure 2

3|F _obs| − 2|F _calc| electron-density OMIT map in the ‘active-site’ region of monomer A of the BthA-I–BPB complex, showing the His48 residue covalently bound with BPB contoured at 1.2 standard deviations. The figure was generated using O (Jones et al., 1990 ▶).