Catalytic domain of phosphoinositide-specific phospholipase C-like phosphodiesterases superfamily
The PI-PLC-like phosphodiesterases superfamily represents the catalytic domains of bacterial phosphatidylinositol-specific phospholipase C (PI-PLC, EC 220.127.116.11), eukaryotic phosphoinositide-specific phospholipase C (PI-PLC, EC 18.104.22.168), glycerophosphodiester phosphodiesterases (GP-GDE, EC 22.214.171.124), sphingomyelinases D (SMases D) (sphingomyelin phosphodiesterase D, EC 126.96.36.199) from spider venom, SMases D-like proteins, and phospholipase D (PLD) from several pathogenic bacteria, as well as their uncharacterized homologs found in organisms ranging from bacteria and archaea to metazoans, plants, and fungi. PI-PLCs are ubiquitous enzymes hydrolyzing the membrane lipid phosphoinositides to yield two important second messengers, inositol phosphates and diacylglycerol (DAG). GP-GDEs play essential roles in glycerol metabolism and catalyze the hydrolysis of glycerophosphodiesters to sn-glycerol-3-phosphate (G3P) and the corresponding alcohols that are major sources of carbon and phosphate. Both, PI-PLCs and GP-GDEs, can hydrolyze the 3'-5' phosphodiester bonds in different substrates, and utilize a similar mechanism of general base and acid catalysis with conserved histidine residues, which consists of two steps, a phosphotransfer and a phosphodiesterase reaction. This superfamily also includes Neurospora crassa ankyrin repeat protein NUC-2 and its Saccharomyces cerevisiae counterpart, Phosphate system positive regulatory protein PHO81, glycerophosphodiester phosphodiesterase (GP-GDE)-like protein SHV3 and SHV3-like proteins (SVLs). The residues essential for enzyme activities and metal binding are not conserved in these sequence homologs, which might suggest that the function of catalytic domains in these proteins might be distinct from those in typical PLC-like phosphodiesterases.
Comment:Phosphoinositide-specific phospholipase C, glycerophosphodiester phosphodiesterases, sphingomyelinases D, and similar proteins hydrolyze the 3'-5' phosphodiester bonds in different substrates, utilizing a similar mechanism of general base and acid catalysis involving two conserved histidine residues.
Comment:Due to replacement of critical catalytic residues, neither Phospholipase C Related but Catalytically Inactive Proteins (PRIP), SHV3, or Neurospora crassa ankyrin repeat protein NUC-2 have PLC or glycerophosphodiester enzymatic activity.
Structure:1GYM_A; the catalytic residues in B. cereus phosphatidylinositol-specific phospholipase C are well conserved in all bacterial PI-PLCs. - View structure with Cn3D
Structure:1DJX_B; the catalytic residues in Phosphoinositide-specific phospholipase C-Delta1 from rat - View structure with Cn3D