Glycerophosphodiester phosphodiesterase domain of Saccharomyces cerevisiae YPL206cp and similar proteins
This subfamily corresponds to the glycerophosphodiester phosphodiesterase domain (GDPD) present in Saccharomyces cerevisiae YPL206cp and uncharacterized hypothetical homologs existing in fungi. The product of S. cerevisiae ORF YPL206c (PGC1), YPL206cp (Pgc1p), displays homology to bacterial and mammalian glycerophosphodiester phosphodiesterases (GP-GDE, EC 22.214.171.124), which catalyzes the degradation of glycerophosphodiesters to produce sn-glycerol-3-phosphate (G3P) and the corresponding alcohols. S. cerevisiae YPL206cp is an integral membrane protein with a single GDPD domain following by a short hydrophobic C-terminal tail that may function as a membrane anchor. This protein plays an essential role in the regulation of the cardiolipin (CL) biosynthetic pathway in yeast by removing the excess phosphatidylglycerol (PG) content of membranes via a phospholipase C-type degradation mechanism. YPL206cp has been characterized as a PG-specific phospholipase C that selectively catalyzes the cleavage of PG, not glycerophosphoinositol (GPI) or glycerophosphocholine (GPC), to diacylglycerol (DAG) and glycerophosphate. Members in this family are distantly related to S. cerevisiae YPL110cp, which selectively hydrolyzes glycerophosphocholine (GPC), not glycerophosphoinositol (GPI), to generate choline and glycerolphosphate, and has been characterized as a cytoplasmic GPC-specific phosphodiesterase.
Comment:The catalytic mechanism of glycerophosphodiester phosphodiesterases is based on the metal ion-dependent general acid-base reaction.
Comment:Based on structure evidence and site-directed mutagenesis of Thermoanaerobacter tengcongensis glycerophosphodiester phosphodiesterase, the catalytic site consists of two conserved histidine residues which serve as general acid and general base in catalyzing the hydrolysis of the 3'-5' phosphodiester bond.