1. Structural insights for fatty acid binding in a Lys49-phospholipase A2: crystal structure of myotoxin II from Bothrops moojeni complexed with stearic acid
- Author
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Watanabe, Leandra, Soares, Andreimar M., Ward, Richard J., Fontes, Marcos R.M., and Arni, Raghuvir K.
- Subjects
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PHOSPHOLIPASES , *FATTY acids , *STEARIC acid , *BOTHROPS , *CARBOXYLIC acids - Abstract
Abstract: The crystal structure of dimeric Lys49-phospholipase A2 myotoxin-II from Bothrops moojeni (MjTX-II) co-crystallized with stearic acid (C18H36O2) has been determined at a resolution of 1.8 Å. The electron density maps permitted the unambiguous inclusion of six stearic acid molecules in the refinement. Two stearic acid molecules could be located in the substrate-binding cleft of each monomer in positions, which favor the interaction of their carboxyl groups with active site residues. The way of binding of stearic acids to this Lys49-PLA2s is analogous to phospholipids and transition state analogues to catalytically active PLA2s. Two additional stearic acid molecules were located at the dimer interface region, defining a hitherto unidentified acyl-binding site on the protein surface. The strictly conserved Lys122 for Lys49-PLA2s may play a fundamental role for stabilization of legend-protein complex. The comparison of MjTX-II/satiric acid complex with other Lys-PLA2s structures whose putative fatty acids were located at their active site is also analysed. Molecular details of the stearic acid/protein interactions provide insights to binding in group I/II PLA2s, and to the possible interactions of Lys49-PLA2s with target membranes. [Copyright &y& Elsevier]
- Published
- 2005
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