The first crystal structure of a phospholipase D

Background: The phospholipase D (PLD) superfamily includes enzymes that are involved in phospholipid metabolism, nucleases, toxins and virus envelope proteins of unknown function. PLD hydrolyzes the terminal phosphodiester bo nd of phospholipids to phosphatidic acid and a hydrophilic constituent. Pho sphatidic acid is a compound that is heavily involved in signal transductio n. PLD also catalyses a transphosphatidylation reaction in the presence of phosphatidylcholine and a short-chained primary or secondary alcohol. Results: The first crystal structure of a 54 kDa PLD has been determined to 1.9 Angstrom resolution using the multiwavelength anomalous dispersion (MA D) method on a single WO4 ion and refined to 1.4 Angstrom resolution. PLD f rom the bacterial source Streptomyces sp. strain PMF consists of a single p olypeptide chain that is folded into two domains. An active site is located at the interface between these domains. The presented structure supports t he proposed superfamily relationship with the published structure of the 16 kDa endonuclease from Salmonella typhimurium. Conclusions: The structure of PLD provides insight into the structure and m ode of action of not only bacterial, plant and mammalian PLDs, but also of a variety of enzymes as diverse as cardiolipin synthases, phosphatidylserin e synthases, toxins, endonucleases, as well as poxvirus envelope proteins h aving a so far unknown function. The common features of these enzymes are t hat they can bind to a phosphodiester moiety, and that most of these enzyme s are active as bi-lobed monomers or dimers.