5VEO

Murine ectonucleotide pyrophosphatase / phosphodiesterase 5 (ENPP5, NPP5), inactive (T72A), in complex with AMP

5VEO の概要

• エントリーDOI: 10.2210/pdb5veo/pdb
• 関連するPDBエントリー: 5VEM 5VEN
• 分子名称: Ectonucleotide pyrophosphatase/phosphodiesterase family member 5, 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, alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose, ... (10 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: 1
• 化学式量合計: 51967.42

構造登録者

Gorelik, A.,Randriamihaja, A.,Illes, K.,Nagar, B. (登録日: 2017-04-05, 公開日: 2017-09-20, 最終更新日: 2024-10-09)

主引用文献

Gorelik, A.,Randriamihaja, A.,Illes, K.,Nagar, B.
A key tyrosine substitution restricts nucleotide hydrolysis by the ectoenzyme NPP5.
FEBS J., 284:3718-3726, 2017

PubMed Abstract: The ecto-nucleotide pyrophosphatase/phosphodiesterase (NPP) family of proteins mediates purinergic signaling by degrading extracellular nucleotides and also participates in phospholipid metabolism. NPP5 (ENPP5) is the least characterized member of this group and its specific role is unknown. This enzyme does not display activity on certain nucleotides and on other typical NPP substrates. In order to gain insights into its function, we determined the crystal structure of human and murine NPP5. Structural comparison with close homologs revealed a key phenylalanine to tyrosine substitution that prevents efficient hydrolysis of nucleotide diphosphates and triphosphates; reversal of this mutation enabled degradation of these molecules. Interestingly, NPP5 is able to cleave nicotinamide adenine dinucleotide (NAD), suggesting a potential role of this enzyme in NAD-based neurotransmission. An NPP5-specific metal binding motif is found adjacent to the active site, although its significance is unclear. These findings expand our understanding of substrate specificity within the NPP family.

PubMed: 28898552
DOI: 10.1111/febs.14266

実験手法

X-RAY DIFFRACTION (1.53 Å)