This subfamily corresponds to the glycerophosphodiester phosphodiesterase domain (GDPD) present in mammalian glycerophosphodiester phosphodiesterase domain-containing protein subtype 5 (GDE2), subtype 2 (GDE3), subtype 1 (GDE6), and their eukaryotic homologs. Mammalian GDE2, GDE3, and GDE6 show very high sequence similarity to each other and have been classified into the same family. Although they are all transmembrane proteins, based on different pattern of tissue distribution, these enzymes might display diverse cellular functions. Mammalian GDE2 is primarily expressed in mature neurons. It selectively hydrolyzes glycerophosphocholine (GPC) and mainly functions in a complex with an antioxidant scavenger peroxiredoxin1 (Prdx1) to control motor neuron differentiation in the spinal cord. Mammalian GDE3 is specifically expressed in bone tissues and spleen. It selectively hydrolyzes extracellular glycerophosphoinositol (GPI) to generate inositol 1-phosphate (Ins1P) and glycerol and functions as an inducer of osteoblast differentiation. Mammalian GDE6 is predominantly expressed in the spermatocytes of testis, and its specific physiological function has not been elucidated yet.
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.