5TCD

Human alkaline sphingomyelinase (ENPP7) in complex with phosphocholine

5TCD の概要

• エントリーDOI: 10.2210/pdb5tcd/pdb
• 分子名称: Ectonucleotide pyrophosphatase/phosphodiesterase family member 7, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (10 entities in total)
• 機能のキーワード: sphingomyelinase, sphingomyelin, phosphocholine, glycosylphosphatidylinositol, hydrolase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 55640.03

構造登録者

Gorelik, A.,Liu, F.,Illes, K.,Nagar, B. (登録日: 2016-09-14, 公開日: 2017-03-22, 最終更新日: 2024-11-06)

主引用文献

Gorelik, A.,Liu, F.,Illes, K.,Nagar, B.
Crystal structure of the human alkaline sphingomyelinase provides insights into substrate recognition.
J. Biol. Chem., 292:7087-7094, 2017

PubMed Abstract: Absorption of dietary sphingomyelin (SM) requires its initial degradation into ceramide, a process catalyzed by the intestinal enzyme alkaline sphingomyelinase (alk-SMase, NPP7, ). alk-SMase belongs to the nucleotide pyrophosphatase/phosphodiesterase (NPP) family, the members of which hydrolyze nucleoside phosphates, phospholipids, and other related molecules. NPP7 is the only paralog that can cleave SM, and its activity requires the presence of bile salts, a class of physiological anionic detergents. To elucidate the mechanism of substrate recognition, we determined the crystal structure of human alk-SMase in complex with phosphocholine, a reaction product. Although the overall fold and catalytic center are conserved relative to other NPPs, alk-SMase recognizes the choline moiety of its substrates via an NPP7-specific aromatic box composed of tyrosine residues. Mutational analysis and enzymatic activity assays identified features on the surface of the protein-a cationic patch and a unique hydrophobic loop-that are essential for accessing SM in bile salt micelles. These results shed new light on substrate specificity determinants within the NPP enzyme family.

PubMed: 28292932
DOI: 10.1074/jbc.M116.769273

実験手法

X-RAY DIFFRACTION (2.4 Å)