5M0M
Structure-based evolution of a hybrid steroid series of Autotaxin inhibitors
Summary for 5M0M
| Entry DOI | 10.2210/pdb5m0m/pdb |
| Descriptor | Ectonucleotide pyrophosphatase/phosphodiesterase family member 2, (2R)-2-hydroxy-3-(phosphonooxy)propyl (9E)-octadec-9-enoate, alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-6)]alpha-D-mannopyranose-(1-6)-[alpha-D-mannopyranose-(1-3)]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 | medicinal chemistry, structure based design, autotaxin, hydrolase |
| Biological source | Rattus norvegicus (Rat) |
| Total number of polymer chains | 1 |
| Total formula weight | 100662.48 |
| Authors | Keune, W.-J.,Heidebrecht, T.,Perrakis, A. (deposition date: 2016-10-05, release date: 2017-08-16, Last modification date: 2024-01-17) |
| Primary citation | Keune, W.J.,Potjewyd, F.,Heidebrecht, T.,Salgado-Polo, F.,Macdonald, S.J.,Chelvarajan, L.,Abdel Latif, A.,Soman, S.,Morris, A.J.,Watson, A.J.,Jamieson, C.,Perrakis, A. Rational Design of Autotaxin Inhibitors by Structural Evolution of Endogenous Modulators. J. Med. Chem., 60:2006-2017, 2017 Cited by PubMed Abstract: 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. PubMed: 28165241DOI: 10.1021/acs.jmedchem.6b01743 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.1 Å) |
Structure validation
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