5EGE

Structure of ENPP6, a choline-specific glycerophosphodiester-phosphodiesterase

5EGE の概要

• エントリーDOI: 10.2210/pdb5ege/pdb
• 関連するPDBエントリー: 5EGH
• 分子名称: Ectonucleotide pyrophosphatase/phosphodiesterase family member 6, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[beta-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (7 entities in total)
• 機能のキーワード: choline metabolism, phosphodiesterase, hydrolase
• 由来する生物種: Mus musculus (Mouse)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 204818.56

構造登録者

Morita, J.,Kano, K.,Kato, K.,Takita, H.,Ishitani, R.,Nishimasu, H.,Nureki, O.,Aoki, J. (登録日: 2015-10-27, 公開日: 2016-03-09, 最終更新日: 2020-07-29)

主引用文献

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.
Structure and biological function of ENPP6, a choline-specific glycerophosphodiester-phosphodiesterase
Sci Rep, 6:20995-20995, 2016

PubMed Abstract: Choline 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.

PubMed: 26888014
DOI: 10.1038/srep20995

実験手法

X-RAY DIFFRACTION (2 Å)