Glycerophosphodiester phosphodiesterase domain of mammalian glycerophosphodiester phosphodiesterase GDE2 and similar proteins
This subfamily corresponds to the glycerophosphodiester phosphodiesterase domain (GDPD) present in mammalian GDE2 (also known as glycerophosphodiester phosphodiesterase domain-containing protein 5 (GDPD5)) and their metazoan homologs. Mammalian GDE2 is transmembrane protein primarily expressed in mature neurons. It is a mammalian homolog of bacterial glycerophosphodiester phosphodiesterases (GP-GDEs, EC 188.8.131.52), which catalyze the hydrolysis of various glycerophosphodiesters, and produce sn-glycerol-3-phosphate (G3P) and the corresponding alcohols. Mammalian GDE2 selectively hydrolyzes glycerophosphocholine (GPC) and has been characterized as GPC-GDE (EC 184.108.40.206) that contributes to osmotic regulation of cellular GPC. Mammalian GDE2 functions in a complex with an antioxidant scavenger peroxiredoxin1 (Prdx1) to control motor neuron differentiation in the spinal cord. Mammalian GDE2 also plays a critical role for retinoid-induced neuronal outgrowth. The catalytic activity of GDPD domain is essential for mammalian GDE2 cellular function.
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.