A distant evolutionary relationship between GPI-specific phospholipase D and bacterial phosphatidylcholine-preferring phospholipase C.
In eukaryotes some surface proteins are attached to the plasma membrane by a glycosylphosphatidylinositol (GPI) anchor. A GPI-specific phospholipase D (GPI-PLD) activity has been characterized and implicated in the regulation of anchoring, thereby influencing the dispersal of anchored proteins or their maintenance on the cell surface, and possibly in cell signalling. Despite its biological and medical importance, little is known of the structure of GPI-PLD. Here, a distant relationship between the catalytic domains of GPI-PLD and some bacterial phospholipases C is demonstrated. A model of the GPI-PLD catalytic site sheds light on catalysis and highlights possibilities for design of improved and more specific GPI-PLD inhibitors. The databases contain hitherto unnoticed close homologues of GPI-PLD from yeast and Dictyostelium discoideum.
Rigden
Daniel J
DJ
School of Biological Sciences, University of Liverpool, Crown Street, Liverpool L69 7ZB, UK. drigden@liv.ac.uk
D000595:Amino Acid Sequence; D000818:Animals; D001419:Bacteria / Q000201:enzymology / Q000235:genetics; D005075:Biological Evolution; D017124:Conserved Sequence; D004023:Dictyostelium / Q000201:enzymology; D008969:Molecular Sequence Data; D010713:Phosphatidylcholines / Q000378:metabolism; D010739:Phospholipase D / Q000737:chemistry / Q000235:genetics*; D017433:Protein Structure, Secondary; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity; D010738:Type C Phospholipases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
D010713:Phosphatidylcholines; D029701:Saccharomyces cerevisiae Proteins; D010738:Type C Phospholipases; D010739:Phospholipase D; C065017:glycoprotein phospholipase D