5LQQ

Structure of Autotaxin (ENPP2) with LM350

5LQQ の概要

• エントリーDOI: 10.2210/pdb5lqq/pdb
• 分子名称: Ectonucleotide pyrophosphatase/phosphodiesterase family member 2, alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]alpha-D-mannopyranose-(1-6)-[alpha-D-mannopyranose-(1-3)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ZINC ION, ... (8 entities in total)
• 機能のキーワード: autotaxin, enpp2, inhibitor, lm350, ectonucleotide pyrophosphatase/phosphodiesterase, hydrolase
• 由来する生物種: Rattus norvegicus (Norway Rat)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 98291.71

構造登録者

Keune, W.J.,Heidebrecht, T.,Castelmur, E.,Joosten, R.P.,Perrakis, A. (登録日: 2016-08-17, 公開日: 2016-12-28, 最終更新日: 2024-10-16)

主引用文献

Miller, L.M.,Keune, W.J.,Castagna, D.,Young, L.C.,Duffy, E.L.,Potjewyd, F.,Salgado-Polo, F.,Engel Garcia, P.,Semaan, D.,Pritchard, J.M.,Perrakis, A.,Macdonald, S.J.,Jamieson, C.,Watson, A.J.
Structure-Activity Relationships of Small Molecule Autotaxin Inhibitors with a Discrete Binding Mode.
J. Med. Chem., 60:722-748, 2017

PubMed Abstract: Autotaxin (ATX) is a secreted enzyme responsible for the hydrolysis of lysophosphatidylcholine (LPC) to the bioactive lysophosphatidic acid (LPA) and choline. The ATX-LPA signaling pathway is implicated in cell survival, migration, and proliferation; thus, the inhibition of ATX is a recognized therapeutic target for a number of diseases including fibrotic diseases, cancer, and inflammation, among others. Many of the developed synthetic inhibitors for ATX have resembled the lipid chemotype of the native ligand; however, a small number of inhibitors have been described that deviate from this common scaffold. Herein, we report the structure-activity relationships (SAR) of a previously reported small molecule ATX inhibitor. We show through enzyme kinetics studies that analogues of this chemotype are noncompetitive inhibitors, and by using a crystal structure with ATX we confirm the discrete binding mode.

PubMed: 27982588
DOI: 10.1021/acs.jmedchem.6b01597

実験手法

X-RAY DIFFRACTION (2.4 Å)