Crystal structure of phospholipase A2 from Indian cobra reveals a trimeric association.
Phospholipase A2 (PLA2) from Indian cobra venom (Naja naja naja) was crystallized from ethanol in space group P4(3)2(1)2 in the presence of Ca2+. The x-ray crystal structure was determined to 2.3-A resolution by molecular replacement techniques using a theoretical model constructed from homologous segments of the bovine pancreatic, porcine pancreatic, and rattlesnake venom crystal structures. The structure was refined to an R value of 0.174 for 17,542 reflections between 6.0- and 2.3-A resolution (F > 2 sigma), including 148 water molecules. The 119-amino acid enzyme has an overall architecture strikingly similar to the other known PLA2 structures with regions implicated in catalysis showing the greatest structural conservation. Unexpectedly, three monomers were found to occupy the asymmetric unit and are oriented with their catalytic sites facing the pseudo-threefold axis with approximately 15% of the solvent accessible surface of each monomer buried in trimer contacts. The majority of the interactions at the subunit interfaces are made by residues unique to PLA2 sequences from cobra and krait venoms. The possible relevance of this unique trimeric structure is considered.
Fremont
D H
DH
Department of Chemistry, University of California, San Diego, La Jolla 92093.
Anderson
D H
DH
Wilson
I A
IA
Dennis
E A
EA
Xuong
N H
NH
D000595:Amino Acid Sequence; D000818:Animals; D004546:Elapid Venoms; D046911:Macromolecular Substances; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010179:Pancreas / Q000201:enzymology; D010741:Phospholipases A / Q000737:chemistry* / Q000302:isolation & purification; D054467:Phospholipases A2; D011487:Protein Conformation; D012911:Snakes; D013552:Swine; D014961:X-Ray Diffraction
D004546:Elapid Venoms; D046911:Macromolecular Substances; D010741:Phospholipases A; D054467:Phospholipases A2