View source for 9wp5


==The crystal structure of PDE4D with Pinoresinol Dimethyl Ether==
<StructureSection load='9wp5' size='340' side='right'caption='[[9wp5]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9wp5]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9WP5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9WP5 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1EYL:(3~{S},3~{a}~{R},6~{S},6~{a}~{R})-3,6-bis(3,4-dimethoxyphenyl)-1,3,3~{a},4,6,6~{a}-hexahydrofuro[3,4-c]furan'>A1EYL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=9wp5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9wp5 OCA], [https://pdbe.org/9wp5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9wp5 RCSB], [https://www.ebi.ac.uk/pdbsum/9wp5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9wp5 ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/PDE4D_HUMAN PDE4D_HUMAN] Note=Genetic variations in PDE4D might be associated with susceptibility to stroke. PubMed:17006457 states that association with stroke has to be considered with caution.  Defects in PDE4D are the cause of acrodysostosis type 2, with or without hormone resistance (ACRDYS2) [MIM:[https://omim.org/entry/614613 614613]. ACRDYS2 is a pleiotropic disorder characterized by skeletal, endocrine, and neurological abnormalities. Skeletal features include brachycephaly, midface hypoplasia with a small upturned nose, brachydactyly, and lumbar spinal stenosis. Endocrine abnormalities include hypothyroidism and hypogonadism in males and irregular menses in females. Developmental disability is a common finding but is variable in severity and can be associated with significant behavioral problems.<ref>PMID:22464250</ref> 
== Function ==
[https://www.uniprot.org/uniprot/PDE4D_HUMAN PDE4D_HUMAN] Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes.<ref>PMID:15260978</ref> <ref>PMID:15576036</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
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(50) = 0.90 muM) 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 pi-pi 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.

Discovery of pinoresinol dimethyl ether as a natural PDE4 inhibitor with anti-psoriatic effects.,Liu X, Gu W, Zhou Y, Wu L, Chen Z, Xiao K, Cao Y, Wu Q, Cao Z, Huang S, Li B, Huang YY, Luo HB Bioorg Chem. 2026 Feb;169:109414. doi: 10.1016/j.bioorg.2025.109414. Epub 2025 , Dec 22. PMID:41453305<ref>PMID:41453305</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9wp5" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Huang Y-Y]]
[[Category: Luo H-B]]