X‐ray crystal structure and molecular dynamics simulation of bovine pancreas phospholipase A 2 – n ‐dodecylphosphorylcholine complex

The crystal structure of n ‐dodecylphosphorylcholine ( n ‐C 12 PC)–bovine pancreas phospholipase A 2 (PLA 2 ) complex provided the following structural.characteristics: (1) the dodecyl chain of n ‐C 12 PC was located at the PLA 2 N ‐terminal helical region by hydrophobic interactions, which corresponds to the binding pocket of 2‐acyl fatty acid chain (β‐chain) of the substrate phospholipid, (2) the region from Lys‐53 to Lys‐56 creates a cholinereceiving pocket of n‐C 12 PC and (3) the N‐termillal group of Ala‐1 shifts significantly toward the Tyr‐52 OH group by the binding of the n‐C1 2 PC inhibitor. Since the accuracy of the X‐ray analysis (R = 0.275 at 2.3 Å resolution) was insufficient to establish these important X‐ray insights, the complex structure was further investigated through the molecular dynamics (M D) simulation, assuming a system in aqueous solution at 310K. The M D simulation covering 176 ps showed that the structural characteristics observed by X‐ray analysis are intrinsic and also stable in the dynamic state. Furthermore, the M D simulation made clear that the PLA 2 binding pocket is large enough to permit the conformational fluctuation of the n‐C 12 PC hydrocarbon chain. © 1994 Wiley‐Liss, Inc. © 1994 Wiley‐Liss, Inc.