title: Structure of basic phospholipase A2 from Agkistrodon halys Pallas: implications for its association, hemolytic and anticoagulant activities.
abstract: The basic phospholipase A2 (PLA2) from the venom of Agkistrodon halys Pallas is a potent hemolytic toxin and anticoagulant. Crystal structure of the enzyme complexed with detergent n-octyl beta-D-glucopyranoside (beta-OG) in monoclinic crystal form has been determined to 2.6 A resolution. Beta-OG molecules were found in the hydrophobic channels of the enzyme. SDS-PAGE and dynamic light scattering measurements showed that the enzyme had a strong tendency to dimerise in aqueous solution. In the crystal structure the enzyme molecules associate into a tetramer with pseudo 222 symmetry, and the interfacial recognition site linked dimers constituting the tetramer have intensive interface interactions, and may be stable in solution. The structure reveals a unique positively charged face at the C-terminal region and a characteristic non-cationic 'anticoagulant' region (53-77). The face is supposed to be the hemolytic site, and based on sequence and structure comparison residues Trp70 and Glu53 instead of the basic residues in 'anticoagulant' region might play an important role in the anticoagulant activity.
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Academia Sinica, Beijing, China.
authors.forename: K
authors.initials: K
authors.lastname: Zhao
authors.forename: Y
authors.initials: Y
authors.lastname: Zhou
authors.forename: Z
authors.initials: Z
authors.lastname: Lin
mesh_terms: D017836:Agkistrodon; D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects; D003435:Crotalid Venoms / Q000737:chemistry* / Q000201:enzymology*; D018360:Crystallography, X-Ray; D004591:Electrophoresis, Polyacrylamide Gel; D006461:Hemolysis / Q000187:drug effects; D008958:Models, Molecular; D015394:Molecular Structure; D010741:Phospholipases A / Q000737:chemistry* / Q000494:pharmacology; D054467:Phospholipases A2; D013329:Structure-Activity Relationship
chemical_list: D003435:Crotalid Venoms; D010741:Phospholipases A; D054467:Phospholipases A2