Marchi-Salvador D P, Fernandes C A H, Amui S F, Soares A M, Fontes M R M
Departamento de Física e Biofísica, Instituto de Biociências, UNESP, CP 510, CEP 18618-000, Botucatu-SP, Brazil.
Acta Crystallogr Sect F Struct Biol Cryst Commun. 2006 Jun 1;62(Pt 6):600-3. doi: 10.1107/S174430910601801X. Epub 2006 May 31.
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.
首次实现了非催化性且具有肌毒性的Lys49 - PLA2(矛头蝮蛇毒中的BthTX - I)与BPB抑制剂的结晶。收集了X射线衍射数据,电子密度计算表明该配体与His48残基结合。经BPB化学修饰His48后的BthTX - I显示出显著降低的肌毒性和细胞毒性活性。这表明与PLA2s催化活性相关的His48修饰与Lys49 - PLA2s的其他毒理学活性之间存在生物学关联。