4B56

Structure of ectonucleotide pyrophosphatase-phosphodiesterase-1 (NPP1)

4B56 の概要

• エントリーDOI: 10.2210/pdb4b56/pdb
• 分子名称: ECTONUCLEOTIDE PYROPHOSPHATASE/PHOSPHODIESTERASE FAMILY MEMBER 1, alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (8 entities in total)
• 機能のキーワード: hydrolase
• 由来する生物種: MUS MUSCULUS (MOUSE)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 192777.26

構造登録者

Jansen, S.,Perrakis, A.,Ulens, C.,Winkler, C.,Andries, M.,Joosten, R.P.,Van Acker, M.,Luyten, F.P.,Moolenaar, W.H.,Bollen, M. (登録日: 2012-08-02, 公開日: 2012-09-19, 最終更新日: 2024-11-20)

主引用文献

Jansen, S.,Perrakis, A.,Ulens, C.,Winkler, C.,Andries, M.,Joosten, R.P.,Van Acker, M.,Luyten, F.P.,Moolenaar, W.H.,Bollen, M.
Structure of Npp1, an Ectonucleotide Pyrophosphatase/Phosphodiesterase Involved in Tissue Calcification.
Structure, 20:1948-, 2012

PubMed Abstract: Ectonucleotide pyrophosphatase/phosphodiesterase-1 (NPP1) converts extracellular nucleotides into inorganic pyrophosphate, whereas its close relative NPP2/autotaxin hydrolyzes lysophospholipids. NPP1 regulates calcification in mineralization-competent tissues, and a lack of NPP1 function underlies calcification disorders. Here, we show that NPP1 forms homodimers via intramembrane disulfide bonding, but is also processed intracellularly to a secreted monomer. The structure of secreted NPP1 reveals a characteristic bimetallic active site and a nucleotide-binding groove, but it lacks the lipid-binding pocket and open tunnel present in NPP2. A loop adjacent to the nucleotide-binding site, which is disordered in NPP2, is well ordered in NPP1 and might promote nucleotide binding. Remarkably, the N-terminal somatomedin B-like domains of NPP1, unlike those in NPP2, are flexible and do not contact the catalytic domain. Our results provide a structural basis for the nucleotide pyrophosphatase activity of NPP1 and help to understand how disease-causing mutations may affect NPP1 structure and function.

PubMed: 23041369
DOI: 10.1016/J.STR.2012.09.001

実験手法

X-RAY DIFFRACTION (3 Å)