5egh
From Proteopedia
Structure of ENPP6, a choline-specific glycerophosphodiester-phosphodiesterase in complex with phosphocholine
Structural highlights
Function[ENPP6_MOUSE] Choline-specific glycerophosphodiester phosphodiesterase. The preferred substrate may be lysosphingomyelin (By similarity). Hydrolyzes lysophosphatidylcholine (LPC) to form monoacylglycerol and phosphorylcholine but not lysophosphatidic acid, showing it has a lysophospholipase C activity. Has a preference for LPC with short (12:0 and 14:0) or polyunsaturated (18:2 and 20:4) fatty acids. Also hydrolyzes glycerophosphorylcholine and sphingosylphosphorylcholine efficiently. Hydrolyzes the classical substrate for phospholipase C, p-nitrophenyl phosphorylcholine in vitro, while it does not hydrolyze the classical nucleotide phosphodiesterase substrate, p-nitrophenyl thymidine 5'-monophosphate. Does not hydrolyze diacyl phospholipids such as phosphatidylethanolamine, phosphatidylinositol, phosphatidylserine, phosphatidylglycerol and phosphatidic acid (By similarity).[1] Publication Abstract from PubMedCholine is an essential nutrient for all living cells and is produced extracellularly by sequential degradation of phosphatidylcholine (PC). However, little is known about how choline is produced extracellularly. Here, we report that ENPP6, a choline-specific phosphodiesterase, hydrolyzes glycerophosphocholine (GPC), a degradation product of PC, as a physiological substrate and participates in choline metabolism. ENPP6 is highly expressed in liver sinusoidal endothelial cells and developing oligodendrocytes, which actively incorporate choline and synthesize PC. ENPP6-deficient mice exhibited fatty liver and hypomyelination, well known choline-deficient phenotypes. The choline moiety of GPC was incorporated into PC in an ENPP6-dependent manner both in vivo and in vitro. The crystal structure of ENPP6 in complex with phosphocholine revealed that the choline moiety of the phosphocholine is recognized by a choline-binding pocket formed by conserved aromatic and acidic residues. The present study provides the molecular basis for ENPP6-mediated choline metabolism at atomic, cellular and tissue levels. Structure and biological function of ENPP6, a choline-specific glycerophosphodiester-phosphodiesterase.,Morita J, Kano K, Kato K, Takita H, Sakagami H, Yamamoto Y, Mihara E, Ueda H, Sato T, Tokuyama H, Arai H, Asou H, Takagi J, Ishitani R, Nishimasu H, Nureki O, Aoki J Sci Rep. 2016 Feb 18;6:20995. doi: 10.1038/srep20995. PMID:26888014[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Categories: Aoki, J | Ishitani, R | Kano, K | Kato, K | Morita, J | Nishimasu, H | Nureki, O | Takita, H | Choline metabolism | Hydrolase | Phosphodiesterase
