6FUK
Crystal structure of UTX complexed with 5-carboxy-8-hydroxyquinoline
Summary for 6FUK
| Entry DOI | 10.2210/pdb6fuk/pdb |
| Descriptor | Lysine-specific demethylase 6A, MANGANESE (II) ION, 8-hydroxyquinoline-5-carboxylic acid, ... (8 entities in total) |
| Functional Keywords | jumonji demethylase, inhibitor, oxidoreductase |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 1 |
| Total formula weight | 61098.40 |
| Authors | Esposito, C.,Sledz, P.,Caflisch, A. (deposition date: 2018-02-27, release date: 2018-10-10, Last modification date: 2024-01-17) |
| Primary citation | Esposito, C.,Wiedmer, L.,Caflisch, A. In Silico Identification of JMJD3 Demethylase Inhibitors. J Chem Inf Model, 58:2151-2163, 2018 Cited by PubMed Abstract: In the search for new demethylase inhibitors, we have developed a multistep protocol for in silico screening. Millions of poses generated by high-throughput docking or a 3D-pharmacophore search are first minimized by a classical force field and then filtered by semiempirical quantum mechanical calculations of the interaction energy with a selected set of functional groups in the binding site. The final ranking includes solvation effects which are evaluated in the continuum dielectric approximation (finite-difference Poisson equation). Application of the multistep protocol to JMJD3 jumonji demethylase has resulted in a dozen low-micromolar inhibitors belonging to five different chemical classes. We have solved the crystal structure of JMJD3 inhibitor 8 in the complex with UTX (a demethylase in the same subfamily as JMJD3) which validates the predicted binding mode. Compound 8 is a promising candidate for future optimization as it has a favorable ligand efficiency of 0.32 kcal/mol per nonhydrogen atom. PubMed: 30226987DOI: 10.1021/acs.jcim.8b00539 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2 Å) |
Structure validation
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