Crystallization and preliminary X-ray diffraction analysis of a myotoxic Lys49-PLA2 from Bothrops jararacussu venom complexed with p-bromophenacyl bromide.
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.
Marchi-Salvador
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Departamento de Física e Biofísica, Instituto de Biociências, UNESP, CP 510, CEP 18618-000, Botucatu-SP, Brazil.
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D000098:Acetophenones / Q000737:chemistry*; D000818:Animals; D017837:Bothrops; D002384:Catalysis; D003435:Crotalid Venoms / Q000737:chemistry*; D003460:Crystallization / Q000379:methods; D006639:Histidine / Q000737:chemistry; D010741:Phospholipases A / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D054467:Phospholipases A2; D012997:Solvents; D014961:X-Ray Diffraction
D000098:Acetophenones; D003435:Crotalid Venoms; D012997:Solvents; C078097:bothropstoxin; D006639:Histidine; D010741:Phospholipases A; D054467:Phospholipases A2; C006821:4-bromophenacyl bromide