5LIA
Crystal structure of murine autotaxin in complex with a small molecule inhibitor
Summary for 5LIA
| Entry DOI | 10.2210/pdb5lia/pdb |
| Descriptor | Ectonucleotide pyrophosphatase/phosphodiesterase family member 2, 1,2-ETHANEDIOL, alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-alpha-D-mannopyranose-(1-6)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (11 entities in total) |
| Functional Keywords | lysophospholipase d, autotaxin, enpp2, hydrolase |
| Biological source | Mus musculus (Mouse) |
| Total number of polymer chains | 1 |
| Total formula weight | 98955.72 |
| Authors | Turnbull, A.P.,Shah, P.,Cheasty, A.,Raynham, T.,Pang, L.,Owen, P. (deposition date: 2016-07-14, release date: 2016-11-09, Last modification date: 2024-11-06) |
| Primary citation | Shah, P.,Cheasty, A.,Foxton, C.,Raynham, T.,Farooq, M.,Gutierrez, I.F.,Lejeune, A.,Pritchard, M.,Turnbull, A.,Pang, L.,Owen, P.,Boyd, S.,Stowell, A.,Jordan, A.,Hamilton, N.M.,Hitchin, J.R.,Stockley, M.,MacDonald, E.,Quesada, M.J.,Trivier, E.,Skeete, J.,Ovaa, H.,Moolenaar, W.H.,Ryder, H. Discovery of potent inhibitors of the lysophospholipase autotaxin. Bioorg. Med. Chem. Lett., 26:5403-5410, 2016 Cited by PubMed Abstract: The autotaxin-lysophosphatidic acid (ATX-LPA) axis has been implicated in several disease conditions including inflammation, fibrosis and cancer. This makes ATX an attractive drug target and its inhibition may lead to useful therapeutic agents. Through a high throughput screen (HTS) we identified a series of small molecule inhibitors of ATX which have subsequently been optimized for potency, selectivity and developability properties. This has delivered drug-like compounds such as 9v (CRT0273750) which modulate LPA levels in plasma and are suitable for in vivo studies. X-ray crystallography has revealed that these compounds have an unexpected binding mode in that they do not interact with the active site zinc ions but instead occupy the hydrophobic LPC pocket extending from the active site of ATX together with occupying the LPA 'exit' channel. PubMed: 27780639DOI: 10.1016/j.bmcl.2016.10.036 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.92 Å) |
Structure validation
Download full validation report
