4ZG7
Structural basis for inhibition of human autotaxin by four novel compounds
Summary for 4ZG7
| Entry DOI | 10.2210/pdb4zg7/pdb |
| Related | 4ZG6 4ZG9 4ZGA |
| Descriptor | Ectonucleotide pyrophosphatase/phosphodiesterase family member 2, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ZINC ION, ... (10 entities in total) |
| Functional Keywords | autotaxin, enpp2, inhibitor, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor |
| Biological source | Homo sapiens (Human) |
| Cellular location | Secreted : Q13822 |
| Total number of polymer chains | 1 |
| Total formula weight | 95007.22 |
| Authors | Stein, A.J.,Bain, G.,Hutchinson, J.H.,Evans, J.F. (deposition date: 2015-04-22, release date: 2015-10-14, Last modification date: 2024-10-23) |
| Primary citation | Stein, A.J.,Bain, G.,Prodanovich, P.,Santini, A.M.,Darlington, J.,Stelzer, N.M.,Sidhu, R.S.,Schaub, J.,Goulet, L.,Lonergan, D.,Calderon, I.,Evans, J.F.,Hutchinson, J.H. Structural Basis for Inhibition of Human Autotaxin by Four Potent Compounds with Distinct Modes of Binding. Mol.Pharmacol., 88:982-992, 2015 Cited by PubMed Abstract: Autotaxin (ATX) is a secreted enzyme that hydrolyzes lysophosphatidylcholine to lysophosphatidic acid (LPA). LPA is a bioactive phospholipid that regulates diverse biological processes, including cell proliferation, migration, and survival/apoptosis, through the activation of a family of G protein-coupled receptors. The ATX-LPA pathway has been implicated in many pathologic conditions, including cancer, fibrosis, inflammation, cholestatic pruritus, and pain. Therefore, ATX inhibitors represent an attractive strategy for the development of therapeutics to treat a variety of diseases. Mouse and rat ATX have been crystallized previously with LPA or small-molecule inhibitors bound. Here, we present the crystal structures of human ATX in complex with four previously unpublished, structurally distinct ATX inhibitors. We demonstrate that the mechanism of inhibition of each compound reflects its unique interactions with human ATX. Our studies may provide a basis for the rational design of novel ATX inhibitors. PubMed: 26371182DOI: 10.1124/mol.115.100404 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.75 Å) |
Structure validation
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