InterPro domain: IPR030395

This entry represents the GP-PDE domain.

The glycerophosphodiester phosphodiesterases (GD-PDEs) were initiallycharacterised in bacteria, where they have functional roles for production ofmetabolic carbon and phosphate sources from glycerophosphodiesters and inadherence to and degradation of mammalian host-cell membranes. Mammalian GP-GDEs have been identified more recently and shown to be implicated in severalphysiological functions. GD-PDEs are involved in glycerol metabolism andcatalyze the reaction of glycerophosphodiester and water to alcohol andsn-glycerol-3-phosphate. They display broad specificity forglycerophosphodiesters, such as glycerophosphocholine,glycerophosphoethanolamine, glycerophosphoglycerol andbis(glycerophosphoglycerol).

The GP-PDE domain adopts the ubiquitous triosephosphate isomerase (TIM) barrelalpha/beta fold. The TIM barrel iscomprised of an eight-stranded parallel beta-sheet barrel surrounded by eightalpha-helices. There is a small insertion to the conventional TIM barrelstructure referred to as the GDPD-insertion (GDPD-I). The GDPD-I is comprisedof beta strands, alpha-helices (H3 and H4), and 3/10 helices. Although the TIMbarrel and a small insertion are unique for GP-PDE family, there are subtledifferences in size and topology of each domain [ 1 , 2 ].

Some proteins known to contain a GP-PDE domain are listed below:

• Bacterial glycerophosphoryl diester phosphodiesterase GlpQ (EC 3.1.4.46).
• Bacterial gylcerophosphoryl diester phosphodiesterase UgpQ (EC 3.1.4.46).
• Mammalian glycerophosphodiester phosphodiesterase 1 (GDE1) (EC 3.1.4.44) (or MMIR16) [ 3 ], an integral membrane glycoprotein that interacts with regulator of G protein signaling proteins. It hydrolyzes glycerophosphoinositols (GPIs) producing inositol and glycerol 3-phosphate.
• Mammalian glycerophosphodiester phosphodiesterase domain-containing protein 5 (GDPD5) (EC 3.1.-.-) (or GDE2) [ 4 ].
• Mammalian glycerophosphoinositol inositolphosphodiesterase GDPD2 (or GDE3) (EC 3.1.4.43) [ 5 ], up-regulated during osteoblast differentiation and can affect cell morpholgy. It hydrolyzes glycerophosphoinositol (GroPIns), producing inositol 1-phosphate and glycerol.
• Mammalian glycerophosphodiester phosphodiesterase domain-containing protein 1 (GDPD1) (EC 3.1.-.-) (or GDE4) [ 6 ].
• Mammalian glycerophosphocholine phosphodiesterase GPCPD1 (EC 3.1.4.2) (or GDE5), selectively hydrolyzes glycerophosphocholine (GroPCho) and controls skeletal muscle development [ 7 ].
• Mammalian glycerophosphodiester phosphodiesterase domain-containing protein 4 (GDPD4) (EC 3.1.-.-) (or GDE6) [ 8 ].

1. Crystal structure of a glycerophosphodiester phosphodiesterase (GDPD) from Thermotoga maritima (TM1621) at 1.60 A resolution. Proteins 56, 167-70
2. Crystal structure of glycerophosphodiester phosphodiesterase from Agrobacterium tumefaciens by SAD with a large asymmetric unit. Proteins 65, 514-8
3. GDE1/MIR16 is a glycerophosphoinositol phosphodiesterase regulated by stimulation of G protein-coupled receptors. Proc. Natl. Acad. Sci. U.S.A. 100, 1745-50
4. Isolation and characterization of two serpentine membrane proteins containing glycerophosphodiester phosphodiesterase, GDE2 and GDE6. Gene 337, 173-9
5. Novel membrane protein containing glycerophosphodiester phosphodiesterase motif is transiently expressed during osteoblast differentiation. J. Biol. Chem. 278, 43595-602
6. Isolation, characterization and molecular 3D model of human GDE4, a novel membrane protein containing glycerophosphodiester phosphodiesterase domain. Mol. Membr. Biol. 25, 557-66
7. A novel glycerophosphodiester phosphodiesterase, GDE5, controls skeletal muscle development via a non-enzymatic mechanism. J. Biol. Chem. 285, 27652-63