X-ray structure of bovine pancreatic phospholipase A(2) at atomic resolution

Using synchrotron radiation and a CCD camera, X-ray data have been collecte d from wild-type bovine pancreatic phospholipase A(2) at 100 K to 0.97 Angs trom resolution allowing full anisotropic refinement. The final model has a conventional R factor of 9.44% for all reflections, with a mean standard u ncertainty for the positional parameters of 0.031 Angstrom as calculated fr om inversion of the full positional least-squares matrix. At 0.97 Angstrom resolution, bovine pancreatic phospholipase A(2) reveals for the first time that its rigid scaffolding does not preclude flexibility, which probably p lays an important role in the catalytic process. Functionally important reg ions (the interfacial binding site and calcium-binding loop) are located at the molecular surface, where conformational variability is more pronounced . A cluster of 2-methyl-2,4-pentanediol molecules is present at the entranc e of the hydrophobic channel that leads to the catalytic site and mimics th e fatty-acid chains of a substrate analogue. Bovine pancreatic phospholipas e A(2) at atomic resolution is compared with previous crystallographic stru ctures and with models derived from nuclear magnetic resonance studies. Giv en the high structural similarity among extracellular phospholipases A(2) o bserved so far at lower resolution, the results arising from this structura l analysis are expected to be of general validity for this class of enzymes .