A novel family of phospholipase D homologues that includes phospholipid synthases and putative endonucleases: identification of duplicated repeats and potential active site residues

Protein Sci. 1996 May;5(5):914-22. doi: 10.1002/pro.5560050513.


Phosphatidylcholine-specific phospholipase D (PLD) enzymes catalyze hydrolysis of phospholipid phosphodiester bonds, and also transphosphatidylation of phospholipids to acceptor alcohols. Bacterial and plant PLD enzymes have not been shown previously to be homologues or to be homologous to any other protein. Here we show, using sequence analysis methods, that bacterial and plant PLDs show significant sequence similarities both to each other, and to two other classes of phospholipid-specific enzymes, bacterial cardiolipin synthases, and eukaryotic and bacterial phosphatidylserine synthases, indicating that these enzymes form an homologous family. This family is suggested also to include two Poxviridae proteins of unknown function (p37K and protein K4), a bacterial endonuclease (nuc), an Escherichia coli putative protein (o338) containing an N-terminal domain showing similarities with helicase motifs V and VI, and a Synechocystis sp. putative protein with a C-terminal domain likely to possess a DNA-binding function. Surprisingly, four regions of sequence similarity that occur once in nuc and o338, appear twice in all other homologues, indicating that the latter molecules are bi-lobed, having evolved from an ancestor or ancestors that underwent a gene duplication and fusion event. It is suggested that, for each of these enzymes, conserved histidine, lysine, aspartic acid, and/or asparagine residues may be involved in a two-step ping pong mechanism involving an enzyme-substrate intermediate.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Bacteria / enzymology
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / classification*
  • Binding Sites
  • DNA Helicases / chemistry
  • DNA Helicases / classification
  • Endodeoxyribonucleases / chemistry
  • Endodeoxyribonucleases / classification
  • Membrane Proteins*
  • Molecular Sequence Data
  • Multigene Family*
  • Phospholipase D / chemistry
  • Phospholipase D / classification*
  • Phospholipase D / genetics
  • Plant Proteins / chemistry
  • Plant Proteins / classification*
  • Plants / enzymology
  • Poxviridae / enzymology
  • Repetitive Sequences, Nucleic Acid
  • Sequence Alignment
  • Sequence Homology, Amino Acid*
  • Transferases (Other Substituted Phosphate Groups) / chemistry
  • Transferases (Other Substituted Phosphate Groups) / classification
  • Viral Proteins / chemistry
  • Viral Proteins / classification*


  • Bacterial Proteins
  • Membrane Proteins
  • Plant Proteins
  • Viral Proteins
  • Transferases (Other Substituted Phosphate Groups)
  • cardiolipin synthetase
  • Endodeoxyribonucleases
  • Phospholipase D
  • DNA Helicases

Associated data

  • GENBANK/R34925
  • GENBANK/R83570
  • GENBANK/T76232
  • GENBANK/T88610
  • GENBANK/Z45777