4LR2

Crystal Structure of Human ENPP4 (apo)

4LR2 の概要

• エントリーDOI: 10.2210/pdb4lr2/pdb
• 関連するPDBエントリー: 4LQY 4LR0 4LR1 4LR5
• 分子名称: Bis(5'-adenosyl)-triphosphatase ENPP4, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total)
• 機能のキーワード: npp4, enpp4, phosphodiesterase, hydrolase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cell membrane ; Single-pass type I membrane protein : Q9Y6X5
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 47296.69

構造登録者

Albright, R.A.,Braddock, D.T. (登録日: 2013-07-19, 公開日: 2013-12-18, 最終更新日: 2024-11-20)

主引用文献

Albright, R.A.,Ornstein, D.L.,Cao, W.,Chang, W.C.,Robert, D.,Tehan, M.,Hoyer, D.,Liu, L.,Stabach, P.,Yang, G.,De La Cruz, E.M.,Braddock, D.T.
Molecular basis of purinergic signal metabolism by ectonucleotide pyrophosphatase/phosphodiesterases 4 and 1 and implications in stroke.
J.Biol.Chem., 289:3294-3306, 2014

PubMed Abstract: NPP4 is a type I extracellular membrane protein on brain vascular endothelium inducing platelet aggregation via the hydrolysis of Ap3A, whereas NPP1 is a type II extracellular membrane protein principally present on the surface of chondrocytes that regulates tissue mineralization. To understand the metabolism of purinergic signals resulting in the physiologic activities of the two enzymes, we report the high resolution crystal structure of human NPP4 and explore the molecular basis of its substrate specificity with NPP1. Both enzymes cleave Ap3A, but only NPP1 can hydrolyze ATP. Comparative structural analysis reveals a tripartite lysine claw in NPP1 that stabilizes the terminal phosphate of ATP, whereas the corresponding region of NPP4 contains features that hinder this binding orientation, thereby inhibiting ATP hydrolysis. Furthermore, we show that NPP1 is unable to induce platelet aggregation at physiologic concentrations reported in human blood, but it could stimulate platelet aggregation if localized at low nanomolar concentrations on vascular endothelium. The combined studies expand our understanding of NPP1 and NPP4 substrate specificity and range and provide a rational mechanism by which polymorphisms in NPP1 confer stroke resistance.

PubMed: 24338010
DOI: 10.1074/jbc.M113.505867

実験手法

X-RAY DIFFRACTION (1.5 Å)