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 bond of phospholipids to phosphatidic acid and a hydrophilic constituent. Phosphatidic acid is a compound that is heavily involved in signal transduction. 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 A resolution using the multiwavelength anomalous dispersion (MAD) method on a single WO(4) ion and refined to 1.4 A resolution. PLD from the bacterial source Streptomyces sp. strain PMF consists of a single polypeptide chain that is folded into two domains. An active site is located at the interface between these domains. The presented structure supports the 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 mode of action of not only bacterial, plant and mammalian PLDs, but also of a variety of enzymes as diverse as cardiolipin synthases, phosphatidylserine synthases, toxins, endonucleases, as well as poxvirus envelope proteins having a so far unknown function. The common features of these enzymes are that they can bind to a phosphodiester moiety, and that most of these enzymes are active as bi-lobed monomers or dimers.
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 bond of phospholipids to phosphatidic acid and a hydrophilic constituent. Phosphatidic acid is a compound that is heavily involved in signal transduction. 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 A resolution using the multiwavelength anomalous dispersion (MAD) method on a single WO(4) ion and refined to 1.4 A resolution. PLD from the bacterial source Streptomyces sp. strain PMF consists of a single polypeptide chain that is folded into two domains. An active site is located at the interface between these domains. The presented structure supports the 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 mode of action of not only bacterial, plant and mammalian PLDs, but also of a variety of enzymes as diverse as cardiolipin synthases, phosphatidylserine synthases, toxins, endonucleases, as well as poxvirus envelope proteins having a so far unknown function. The common features of these enzymes are that they can bind to a phosphodiester moiety, and that most of these enzymes are active as bi-lobed monomers or dimers.
Authors: Saulius Grazulis; Elena Manakova; Manfred Roessle; Matthias Bochtler; Giedre Tamulaitiene; Robert Huber; Virginijus Siksnys Journal: Proc Natl Acad Sci U S A Date: 2005-10-24 Impact factor: 11.205
Authors: Najim Lahrouchi; Alex V Postma; Christian M Salazar; Daniel M De Laughter; Fleur Tjong; Lenka Piherová; Forrest Z Bowling; Dominic Zimmerman; Elisabeth M Lodder; Asaf Ta-Shma; Zeev Perles; Leander Beekman; Aho Ilgun; Quinn Gunst; Mariam Hababa; Doris Škorić-Milosavljević; Viktor Stránecký; Viktor Tomek; Peter de Knijff; Rick de Leeuw; Jamille Y Robinson; Sabrina C Burn; Hiba Mustafa; Matthew Ambrose; Timothy Moss; Jennifer Jacober; Dmitriy M Niyazov; Barry Wolf; Katherine H Kim; Sara Cherny; Andreas Rousounides; Aphrodite Aristidou-Kallika; George Tanteles; Bruel Ange-Line; Anne-Sophie Denommé-Pichon; Christine Francannet; Damara Ortiz; Monique C Haak; Arend D.J. Ten Harkel; Gwendolyn Tr Manten; Annemiek C Dutman; Katelijne Bouman; Monia Magliozzi; Francesca Clementina Radio; Gijs We Santen; Johanna C Herkert; H Alex Brown; Orly Elpeleg; Maurice Jb van den Hoff; Barbara Mulder; Michael V Airola; Stanislav Kmoch; Joey V Barnett; Sally-Ann Clur; Michael A Frohman; Connie R Bezzina Journal: J Clin Invest Date: 2021-03-01 Impact factor: 14.808
Authors: Bruce D Levy; Lorraine Hickey; Andrew J Morris; Mykol Larvie; Raquel Keledjian; Nicos A Petasis; Gerard Bannenberg; Charles N Serhan Journal: Br J Pharmacol Date: 2005-10 Impact factor: 8.739
Authors: Pankaj Dhonukshe; Ana M Laxalt; Joachim Goedhart; Theodorus W J Gadella; Teun Munnik Journal: Plant Cell Date: 2003-09-24 Impact factor: 11.277