6LEH
Crystal structure of Autotaxin in complex with an inhibitor
Summary for 6LEH
| Entry DOI | 10.2210/pdb6leh/pdb |
| Descriptor | Ectonucleotide pyrophosphatase/phosphodiesterase family member 2, 1,2-ETHANEDIOL, ethyl 2-[2-(4-chlorophenyl)-7-methyl-5-oxidanylidene-imidazo[1,2-a]pyrimidin-8-yl]ethanoate, ... (12 entities in total) |
| Functional Keywords | hydrolase |
| Biological source | Mus musculus (Mouse) |
| Total number of polymer chains | 1 |
| Total formula weight | 99672.37 |
| Authors | Nishimasu, H.,Osamu, N. (deposition date: 2019-11-25, release date: 2020-03-18, Last modification date: 2023-11-22) |
| Primary citation | Kawaguchi, M.,Okabe, T.,Okudaira, S.,Hama, K.,Kano, K.,Nishimasu, H.,Nakagawa, H.,Ishitani, R.,Kojima, H.,Nureki, O.,Aoki, J.,Nagano, T. Identification of PotentIn VivoAutotaxin Inhibitors that Bind to Both Hydrophobic Pockets and Channels in the Catalytic Domain. J.Med.Chem., 63:3188-3204, 2020 Cited by PubMed Abstract: Autotaxin (ATX, also known as ENPP2) is a predominant lysophosphatidic acid (LPA)-producing enzyme in the body, and LPA regulates various physiological functions, such as angiogenesis and wound healing, as well as pathological functions, including proliferation, metastasis, and fibrosis, via specific LPA receptors. Therefore, the ATX-LPA axis is a promising therapeutic target for dozens of diseases, including cancers, pulmonary and liver fibroses, and neuropathic pain. Previous structural studies revealed that the catalytic domain of ATX has a hydrophobic pocket and a hydrophobic channel; these serve to recognize the substrate, lysophosphatidylcholine (LPC), and deliver generated LPA to LPA receptors on the plasma membrane. Most reported ATX inhibitors bind to either the hydrophobic pocket or the hydrophobic channel. Herein, we present a unique ATX inhibitor that binds mainly to the hydrophobic pocket and also partly to the hydrophobic channel, inhibiting ATX activity with high potency and selectivity and . Notably, our inhibitor can rescue the cardia bifida (two hearts) phenotype in ATX-overexpressing zebrafish embryos. PubMed: 32134652DOI: 10.1021/acs.jmedchem.9b01967 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2 Å) |
Structure validation
Download full validation report
