| Structural highlights
5m0m is a 1 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , , , , , , , , , , |
| Activity: | Alkylglycerophosphoethanolamine phosphodiesterase, with EC number 3.1.4.39 |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Publication Abstract from PubMed
Autotaxin produces the bioactive lipid lysophosphatidic acid (LPA) and is a drug target of considerable interest for numerous pathologies. We report the expedient, structure-guided evolution of weak physiological allosteric inhibitors (bile salts) into potent competitive Autotaxin inhibitors that do not interact with the catalytic site. Functional data confirms that our lead compound attenuates LPA mediated signaling in cells and reduces LPA synthesis in vivo, providing a promising natural product derived scaffold for drug discovery.
Rational Design of Autotaxin Inhibitors by Structural Evolution of Endogenous Modulators.,Keune WJ, Potjewyd F, Heidebrecht T, Salgado-Polo F, Macdonald SJ, Chelvarajan L, Abdel Latif A, Soman S, Morris AJ, Watson AJ, Jamieson C, Perrakis A J Med Chem. 2017 Mar 9;60(5):2006-2017. doi: 10.1021/acs.jmedchem.6b01743. Epub, 2017 Feb 16. PMID:28165241[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Keune WJ, Potjewyd F, Heidebrecht T, Salgado-Polo F, Macdonald SJ, Chelvarajan L, Abdel Latif A, Soman S, Morris AJ, Watson AJ, Jamieson C, Perrakis A. Rational Design of Autotaxin Inhibitors by Structural Evolution of Endogenous Modulators. J Med Chem. 2017 Mar 9;60(5):2006-2017. doi: 10.1021/acs.jmedchem.6b01743. Epub, 2017 Feb 16. PMID:28165241 doi:http://dx.doi.org/10.1021/acs.jmedchem.6b01743
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