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2XR9

Crystal structure of Autotaxin (ENPP2)

Summary for 2XR9
Entry DOI10.2210/pdb2xr9/pdb
Related2XRG
DescriptorECTONUCLEOTIDE 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 Keywordshydrolase, lysophosphatidylcholine, somatomedin, inflammation, metastasis, neuropathic pain, vascular development, neural development
Biological sourceRATTUS NORVEGICUS (NORWAY RAT)
Total number of polymer chains1
Total formula weight99684.71
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 citationHausmann, 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: 21240271
DOI: 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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