The 2.5 A crystal structure of a dimeric phospholipase A2 from the venom of Crotalus atrox

The crystal structure of the dimeric (alpha 2) phospholipase A2 from Crotalus atrox has been determined by multiple isomorphous replacement to 2.5 A resolution. A skeletal model was fit to the electron density, and the stereochemistry of the backbone was idealized. The dimeric molecule is a well defined oblate ellipsoid composed of two covalently identical subunits related by a local dyad axis which is essentially "exact" except for deviations at the periphery induced by ionic lattice contacts with neighboring dimers. As expected, the basic architecture of the individual protomers is similar to the structure of the homologous monomeric bovine enzyme (Dijkstra, B. W., Drenth, J., Kalk, K., and Vandermaalen, P. J. (1978) J. Mol. Biol. 124, 53-60). The intramolecular contact surface between the protomers is extensive and involves the catalytic and calcium-binding sites. Access to an internal cavity formed by the enclosed and abutting active center regions is quite restricted. The putative interfacial recognition surfaces of each protomer are exposed to the solvent but are on opposing surfaces of the ellipsoid, suggesting that both of these regions cannot interact with the same membrane surface simultaneously unless the membrane is distorted from planarity and/or the dimer is significantly modified.