2XR9

Crystal structure of Autotaxin (ENPP2)

2XR9 の概要

• エントリーDOI: 10.2210/pdb2xr9/pdb
• 関連するPDBエントリー: 2XRG
• 分子名称: ECTONUCLEOTIDE PYROPHOSPHATASE/PHOSPHODIESTERASE FAMILY MEMBER 2, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, THIOCYANATE ION, ... (8 entities in total)
• 機能のキーワード: hydrolase, lysophosphatidylcholine, somatomedin, inflammation, metastasis, neuropathic pain, vascular development, neural development
• 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: 99684.71

構造登録者

Kamtekar, S.,Hausmann, J.,Day, J.E.,Christodoulou, E.,Perrakis, A. (登録日: 2010-09-13, 公開日: 2011-01-19, 最終更新日: 2024-11-20)

主引用文献

Hausmann, J.,Kamtekar, S.,Christodoulou, E.,Day, J.E.,Wu, T.,Fulkerson, Z.,Albers, H.M.,van Meeteren, L.A.,Houben, A.J.,van Zeijl, L.,Jansen, S.,Andries, M.,Hall, T.,Pegg, L.E.,Benson, T.E.,Kasiem, M.,Harlos, K.,Kooi, C.W.,Smyth, S.S.,Ovaa, H.,Bollen, M.,Morris, A.J.,Moolenaar, W.H.,Perrakis, A.
Structural basis of substrate discrimination and integrin binding by autotaxin.
Nat. Struct. Mol. Biol., 18:198-204, 2011

PubMed Abstract: Autotaxin (ATX, also known as ectonucleotide pyrophosphatase/phosphodiesterase-2, ENPP2) is a secreted lysophospholipase D that generates the lipid mediator lysophosphatidic acid (LPA), a mitogen and chemoattractant for many cell types. ATX-LPA signaling is involved in various pathologies including tumor progression and inflammation. However, the molecular basis of substrate recognition and catalysis by ATX and the mechanism by which it interacts with target cells are unclear. Here, we present the crystal structure of ATX, alone and in complex with a small-molecule inhibitor. We have identified a hydrophobic lipid-binding pocket and mapped key residues for catalysis and selection between nucleotide and phospholipid substrates. We have shown that ATX interacts with cell-surface integrins through its N-terminal somatomedin B-like domains, using an atypical mechanism. Our results define determinants of substrate discrimination by the ENPP family, suggest how ATX promotes localized LPA signaling and suggest new approaches for targeting ATX with small-molecule therapeutic agents.

PubMed: 21240271
DOI: 10.1038/nsmb.1980

実験手法

X-RAY DIFFRACTION (2.05 Å)