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Cited by 278

The DOI matches its Crossref record; 41 of the 41 references it cites were found in a registry or an index.

Structural basis of substrate discrimination and integrin binding by autotaxin

Open access
Hausmann, Jens, Kamtekar, Satwik, Christodoulou, Evangelos, Day, Jacqueline E, Wu, Tao, Fulkerson, Zachary, Albers, Harald M H G, van Meeteren, Laurens A, Houben, Anna J S, van Zeijl, Leonie, Jansen, Silvia, Andries, Maria, Hall, Troii, Pegg, Lyle E, Benson, Timothy E, Kasiem, Mobien, Harlos, Karl, Kooi, Craig W Vander, Smyth, Susan S, Ovaa, Huib, Bollen, Mathieu, Morris, Andrew J, Moolenaar, Wouter H, Perrakis, Anastassis·2011·Nature Structural & Molecular Biology

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.

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Metadata

Authors
Hausmann, J., Kamtekar, S., Christodoulou, E., Day, J. E., Wu, T., Fulkerson, Z., Albers, H. M. H. G., van Meeteren, L. A., Houben, A. J. S., van Zeijl, L., Jansen, S., Andries, M., Hall, T., Pegg, L. E., Benson, T. E., Kasiem, M., Harlos, K., Kooi, C. W. V., Smyth, S. S., Ovaa, H., Bollen, M., Morris, A. J., Moolenaar, W. H., & Perrakis, A.
Venue
Nature Structural & Molecular Biology
Published
2011-01-16
Volume
18
Issue
2
Pages
198-204
ISSN
  • 1545-9985 (ISSN-L)
  • 1545-9993
OpenAlex
W2096597075
Cited by
278
References
41
FWCI
10.23
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: Structural basis of substrate discrimination and integrin binding by autotaxin. https://app.cochat.ai/papers/10.1038/nsmb.1980
The paper
Hausmann, J., Kamtekar, S., Christodoulou, E., Day, J. E., Wu, T., Fulkerson, Z., Albers, H. M. H. G., van Meeteren, L. A., Houben, A. J. S., van Zeijl, L., Jansen, S., Andries, M., Hall, T., Pegg, L. E., Benson, T. E., Kasiem, M., Harlos, K., Kooi, C. W. V., Smyth, S. S., . . . Perrakis, A. (2011). Structural basis of substrate discrimination and integrin binding by autotaxin. Nature Structural & Molecular Biology. https://doi.org/10.1038/nsmb.1980

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

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