9WP5
The crystal structure of PDE4D with Pinoresinol Dimethyl Ether
This is a non-PDB format compatible entry.
Summary for 9WP5
| Entry DOI | 10.2210/pdb9wp5/pdb |
| Descriptor | 3',5'-cyclic-AMP phosphodiesterase 4D, ZINC ION, MAGNESIUM ION, ... (5 entities in total) |
| Functional Keywords | natural pde4 inhibitor, hydrolase |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 2 |
| Total formula weight | 76365.75 |
| Authors | |
| Primary citation | Liu, X.,Gu, W.,Zhou, Y.,Wu, L.,Chen, Z.,Xiao, K.,Cao, Y.,Wu, Q.,Cao, Z.,Huang, S.,Li, B.,Huang, Y.Y.,Luo, H.B. Discovery of pinoresinol dimethyl ether as a natural PDE4 inhibitor with anti-psoriatic effects. Bioorg.Chem., 169:109414-109414, 2026 Cited by PubMed Abstract: Psoriasis is a complex chronic inflammatory disease that severely impairs patients' quality of life. However, current medications could only control the symptoms but not cure psoriasis with unmet medical needs. Targeting phosphodiesterase 4 (PDE4) represents a validated therapeutic strategy for psoriasis, though the clinical application of existing PDE4 inhibitors is often hampered by systemic side effects. In this study, we identified pinoresinol dimethyl ether (PDME), a natural furanoid lignan previously reported to be isolated from the stem bark of Magnolia Kobus, as a novel PDE4 inhibitor (IC = 0.90 μM) through an integrated virtual screening approach. The binding mode of PDME to PDE4 was clearly elucidated through molecular dynamics simulations, isothermal titration calorimetry, and co-crystal structure analysis, revealing an enthalpy-driven interaction involving key hydrogen bonds with Gln369 and π-π stacking within the hydrophobic clamp. In vitro, PDME significantly suppressed the expression of pro-inflammatory cytokines in keratinocytes. In a murine imiquimod-induced psoriasis model, PDME treatment markedly alleviated psoriatic lesions, reduced skin thickening, and suppressed inflammatory responses. These findings highlight PDME as a promising natural PDE4 inhibitor with significant potential for the treatment of psoriasis. PubMed: 41453305DOI: 10.1016/j.bioorg.2025.109414 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.1 Å) |
Structure validation
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