Three-dimensional structures of human phospholipase A2 from pancreas and synovial fluid by model building

Three-dimensional structures of the enzyme phospholipase A2 (PLA2) from human pancreas and from human synovial fluid were constructed by model building based on high-resolution X-ray crystallographic structures and homology considerations. The structure of the human pancreatic PLA2 was based on the X-ray structure of the highly homologous bovine pancreatic PLA2 (Type I) by amino acid substitution and modification of the C-terminal part followed by geometry relaxation. The structure of the PLA2 from human synovial fluid was constructed from the X-ray structure of PLA2 from Crotalus atrox (Type II) by modification of the calcium binding loop, amino acid substitution, and insertion of two additional amino acid residues followed by geometry relaxation. The structure of the two human PLA2's have been compared and their use as targets for rational design of enzyme inhibitors discussed.