| Abstract
| - We report the structures of the crystallographic dimer of porcine pancreatic IB phospholipaseA2 (PLA2) with either five sulfate or phosphate anions bound. In each structure, one molecule of atetrahedral mimic MJ33 [1-hexadecyl-3-(trifluoroethyl)-sn-glycero-2-phosphomethanol] and the five anionsare shared between the two subunits of the dimer. The sn-2-phosphate of MJ33 is bound in the active siteof one subunit (A), and the alkyl chain extends into the active site slot of the second subunit (B) acrossthe subunit−subunit interface. The two subunits are packed together with a large hydrophobic anddesolvated surface buried between them along with the five anions that define a plane. The anions bindby direct contact with two cationic residues (R6 and K10) per subunit and through closer-range H-bondinginteractions with other polarizable ligands. These features of the “dimer” suggest that the binding ofPLA2 to the anionic groups at the anionic interface may be dominated by coordination through H-bondingwith only a partial charge compensation needed. Remarkably, the plane defined by the contact surface issimilar to the i-face of the enzyme [Ramirez, F., and Jain, M. K. (1991) Proteins: Struct.,Funct.,Genet.9, 229−239], which has been proposed to make contact with the substrate interface for the interfacialcatalytic turnover. Additionally, these structures not only offer a view of the active PLA2 complexed toan anionic interface but also provide insight into the environment of the tetrahedral intermediate in therate-limiting chemical step of the turnover cycle. Taken together, our results offer an atomic-resolutionstructural view of the i-face interactions of the active form of PLA2 associated to an anionic interface.
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