3WK4
Crystal structure of soluble epoxide hydrolase in complex with fragment inhibitor
Summary for 3WK4
| Entry DOI | 10.2210/pdb3wk4/pdb |
| Related | 3WK5 3WK6 3WK7 3WK8 3WK9 3WKA 3WKB 3WKC 3WKD 3WKE |
| Descriptor | Bifunctional epoxide hydrolase 2, MAGNESIUM ION, PHOSPHATE ION, ... (5 entities in total) |
| Functional Keywords | hydrolase, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor |
| Biological source | Homo sapiens (human) |
| Cellular location | Cytoplasm: P34913 |
| Total number of polymer chains | 1 |
| Total formula weight | 63838.06 |
| Authors | Amano, Y.,Yamaguchi, T.,Tanabe, E. (deposition date: 2013-10-17, release date: 2014-04-16, Last modification date: 2024-05-29) |
| Primary citation | Amano, Y.,Yamaguchi, T.,Tanabe, E. Structural insights into binding of inhibitors to soluble epoxide hydrolase gained by fragment screening and X-ray crystallography. Bioorg.Med.Chem., 22:2427-2434, 2014 Cited by PubMed Abstract: Soluble epoxide hydrolase (sEH) is a component of the arachidonic acid cascade and is a candidate target for therapies for hypertension or inflammation. Although many sEH inhibitors are available, their scaffolds are not structurally diverse, and knowledge of their specific interactions with sEH is limited. To obtain detailed structural information about protein-ligand interactions, we conducted fragment screening of sEH, analyzed the fragments using high-throughput X-ray crystallography, and determined 126 fragment-bound structures at high resolution. Aminothiazole and benzimidazole derivatives were identified as novel scaffolds that bind to the catalytic triad of sEH with good ligand efficiency. We further identified fragment hits that bound to subpockets of sEH called the short and long branches. The water molecule conserved in the structure plays an important role in binding to the long branch, whereas Asp496 and the main chain of Phe497 form hydrogen bonds with fragment hits in the short branch. Fragment hits and their crystal structures provide structural insights into ligand binding to sEH that will facilitate the discovery of novel and potent inhibitors of sEH. PubMed: 24656800DOI: 10.1016/j.bmc.2014.03.001 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.11 Å) |
Structure validation
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