Automated docking of phospholipids to the phospholipase D active site: insight into the catalytic mechanism

Streptomyces sp. PMF phospholipase D (PLD) both hydrolyzes and transphosphatidylates phospholipids. The three-dimensional x-ray crystal structure of this enzyme has been recently determined to 1.4 Å resolution. To better understand the structure-function relationships of this enzyme with different potential substrates, automated docking calculations were conducted to model the structures of various PLD/phospholipid complexes. Several parameters, including the identity of the phospholipid head group and the fatty acid chain length, were varied and the effects on the docked structures were investigated. The docking results revealed a delicate balance between head group/active site interactions and hydrophobic binding of the fatty acid chains outside the active site. Specificity is therefore achieved through the use of this balance of forces. In general the docking agrees at least qualitatively well with the limited experimental information available for the Streptomyces PLD