9lo7

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Current revision (21:51, 26 March 2025) (edit) (undo)
 
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'''Unreleased structure'''
 
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The entry 9lo7 is ON HOLD until Paper Publication
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==The crystal structure of PDE4D with 2317b==
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<StructureSection load='9lo7' size='340' side='right'caption='[[9lo7]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[9lo7]] 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=9LO7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9LO7 FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.2000625&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1EKX:methyl+4-[[2-[4-[bis(fluoranyl)methoxy]-3-(cyclopropen-1-ylmethoxy)phenyl]-6-oxidanyl-1-benzofuran-7-yl]oxy]-1~{H}-pyrrole-2-carboxylate'>A1EKX</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=9lo7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9lo7 OCA], [https://pdbe.org/9lo7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9lo7 RCSB], [https://www.ebi.ac.uk/pdbsum/9lo7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9lo7 ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[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>
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== Function ==
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[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>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Psoriasis is a complex chronic inflammatory disease that severely affects the quality of life of patients. However, current medications could only control the symptoms but not cure psoriasis with unmet medical needs. Herein, structure-based optimizations of natural product moracin M (IC(50) of 2.9 muM) led to a novel PDE4 inhibitor L30 with greatly improved potency (IC(50) of 8.6 nM) and remarkable selectivity across other PDEs families (&gt;201-fold). The binding pattern of L30 with PDE4 revealed by cocrystal structure was different from that of roflumilast. Besides, L30 could effectively inhibit the release of inflammatory cytokines and chemokines in Raw264.7 and HaCaT cell lines. Furthermore, topical administration of L30 exhibited significant therapeutic effects in an imiquimod-induced psoriasis mouse model. These findings highlighted the potential of PDE4 inhibitor L30 as a novel lead for the treatment of psoriasis.
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Authors: Huag, Y.-Y., Wu, D., Luo, H.-B.
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Structure-Based Optimization of Moracin M as Potent and Selective PDE4 Inhibitors with Antipsoriasis Effects.,Zhang F, Zheng T, Wang X, Chen Y, Zhang F, Liu X, Wang S, Yang G, Xie S, Wu Q, Xu C, Zhou Q, Wu D, Luo HB, Huang YY J Med Chem. 2025 Mar 11. doi: 10.1021/acs.jmedchem.5c00266. PMID:40066994<ref>PMID:40066994</ref>
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Description: The crystal structure of PDE4D with 2317b
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[Category: Unreleased Structures]]
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</div>
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[[Category: Wu, D]]
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<div class="pdbe-citations 9lo7" style="background-color:#fffaf0;"></div>
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[[Category: Luo, H.-B]]
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== References ==
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[[Category: Huag, Y.-Y]]
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Homo sapiens]]
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[[Category: Large Structures]]
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[[Category: Huag Y-Y]]
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[[Category: Luo H-B]]
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[[Category: Wu D]]

Current revision

The crystal structure of PDE4D with 2317b

PDB ID 9lo7

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