2XR9
Crystal structure of Autotaxin (ENPP2)
Summary for 2XR9
| Entry DOI | 10.2210/pdb2xr9/pdb |
| Related | 2XRG |
| Descriptor | 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) |
| Functional Keywords | hydrolase, lysophosphatidylcholine, somatomedin, inflammation, metastasis, neuropathic pain, vascular development, neural development |
| Biological source | RATTUS NORVEGICUS (NORWAY RAT) |
| Total number of polymer chains | 1 |
| Total formula weight | 99684.71 |
| Authors | Kamtekar, S.,Hausmann, J.,Day, J.E.,Christodoulou, E.,Perrakis, A. (deposition date: 2010-09-13, release date: 2011-01-19, Last modification date: 2023-12-20) |
| Primary citation | 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 Cited by 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: 21240271DOI: 10.1038/nsmb.1980 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.05 Å) |
Structure validation
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