9XS7
Factor inhibiting HIF-1 alpha in complex with Mn(II) and rhein
Summary for 9XS7
| Entry DOI | 10.2210/pdb9xs7/pdb |
| Descriptor | Hypoxia-inducible factor 1-alpha inhibitor, 4,5-dihydroxy-9,10-dioxo-9,10-dihydroanthracene-2-carboxylic acid, MANGANESE (II) ION, ... (4 entities in total) |
| Functional Keywords | factor inhibiting hif-1 alpha, dioxygenase, oxidoreductase |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 40667.44 |
| Authors | |
| Primary citation | Akhsanitaqwim, Y.,Nakashima, Y.,Ikumi, N.,Morita, H. Structural Insights into Metal-Chelating Natural Inhibitors of Factor Inhibiting HIF-1 alpha. J.Nat.Prod., 2026 Cited by PubMed Abstract: Factor inhibiting HIF-1α (FIH) is a 2-oxoglutarate-dependent oxygenase that controls hypoxia signaling and metabolic homeostasis by hydroxylating HIF-1α. Although selective pharmacological inhibition of FIH represents an emerging therapeutic strategy for metabolic disorders, structurally diverse natural inhibitors remain largely unexplored. Here, we identified five natural FIH inhibitors spanning distinct phytochemical classes, including three flavonoids (wogonin, luteolin, morin), a coumarin (isofraxidin), and an anthraquinone (rhein). Co-crystal structures revealed that structurally diverse natural products converge on a common bidentate metal-chelation geometry within the FIH active site despite substantial differences in scaffold architecture. Among these inhibitors, wogonin most closely mimicked the orientation of the HIF-1α Asn803 side chain within the substrate-binding cleft, resulting in inhibitory potency comparable to that of the 2-oxoglutarate analog -oxalylglycine. These findings establish the first structural framework for natural-product-based FIH inhibition and demonstrate that structurally distinct natural inhibitors adopt a conserved metal-chelation geometry within the FIH active site. This framework provides a basis for the future development of metabolically oriented FIH inhibitors. PubMed: 42455177DOI: 10.1021/acs.jnatprod.6c00734 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.51 Å) |
Structure validation
No wwPDB Validation report is currently available for this entry.
