Crystal structure of a novel phospholipase A2 from Naja naja sagittifera at 1.5 A resolution
Secretory phospholipase A2s (PLA2s), the structurally-homologous enzymes share a common qualitative catalytic site, but differ greatly in their pharmacological properties and toxicities. There has been a recognizable pattern of mutations in the primary sequence of PLA2s that alter their catalytic properties significantly. In the present study, the amino acid sequence and the three-dimensional structure of a new isoform of PLA2 from crude venom of Indian cobra sub-species Naja naja sagittijera
... naja sagittijera (N.n.s.) has been determined by X-ray crystallography. The crystal structure has revealed several novel features of PLA2 folding and furiction. It contains 913 protein atoms and one each of Ca 2 +, phosphate and acetate ions with 142 solvent water molecules. A Ca 2 + ion is present in the calcium-binding loop and forms a seven-fold coordination with a distorted" pentagonal bipyramidal geometry. One of the coordination linkages is with the acetate ion, instead of the conserved water molecule. The presence of Lys at position 31 has a stabilizing effect on the loop Tyr 25-Cys 29 by interacting 'with carbonyl oxygen atoms of Tyr 25, Gly 26 and Cys 29. In turn, it lends stability to the Ca 2 +-binding loop as well. Another unique feature of the PLA2 structure is the formation of an intrastrand hydrogen bond, involving Oy of Thr 73 and O£2 of Glu 71, thus helping the~-wing to act as a sharp arrow for insertion into other molecules. Yet another important feature of this PLA2 pertains to the conformation of its C-terminal segment, which is stabilized by a unique hydrogen bond through carbonyl oxygen of Lys 116 and N82 of Asn 120. This structural feature may be useful in the molecular recognition of the PLA2 through C-terminal segment.