Open AccessSequence‐induced trimerization of phospholipase A 2 : structure of a trimeric isoform of PLA 2 from common krait ( Bungarus caeruleus ) at 2.5 Å resolution
Author(s) -
Singh Garima,
Gourinath S.,
Saravanan K.,
Sharma Sujata,
Bhanumathi S.,
Betzel Ch.,
Srinivasan A.,
Singh T. P.
Publication year - 2005
Publication title -
acta crystallographica section f
Language(s) - English
Resource type - Journals
ISSN - 1744-3091
DOI - 10.1107/s1744309104025503
Subject(s) - pentaerythritol , chemistry , venom , molecule , trimer , crystallography , stereochemistry , oligomer , polymer chemistry , dimer , biochemistry , organic chemistry , fire retardant
The venom of the common Indian krait ( Bungarus caeruleus ) contains about a dozen isoforms of phospholipase A 2 (PLA 2 ), which exist in different oligomeric forms as well as in complexes with low‐molecular‐weight ligands. The basic objective of multimerization and complexation is either to inactivate PLA 2 in the venom for long‐term storage, to generate a new PLA 2 function or to make a more lethal assembly. The current isoform was isolated from the venom of B. caeruleus . Dynamic light‐scattering studies indicated the presence of a stable trimeric association of this PLA 2 . Its primary sequence was determined by cDNA cloning. The purified protein was crystallized with 2.8 M NaCl as a precipitating agent using the sitting‐drop vapour‐diffusion method. The crystals belonged to the monoclinic space group C 2, with unit‐cell parameters a = 80.9, b = 80.5, c = 57.1 Å, β = 90.3°. The structure was refined to a final R factor of 0.198. This is a novel trimeric PLA 2 structure in which the central pore formed by the association of three molecules is filled with water molecules. The interactions across the pore take place via multiple water bridges primarily to the side chains of Arg, Lys and Thr residues. Approximately 12% of the total solvent‐accessible surface area is buried in the core of the trimer. The active sites of all three molecules are located on the surface and are fully exposed to the solvent, resulting in a highly potent enzymatic unit.