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9s1i
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of human Dihydroorotate Dehydrogenase in complex with arzanol== | |
| + | <StructureSection load='9s1i' size='340' side='right'caption='[[9s1i]], [[Resolution|resolution]] 1.61Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[9s1i]] is a 1 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=9S1I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9S1I 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]] 1.61Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1JKW:3-[[3-ethanoyl-5-(3-methylbut-2-enyl)-2,4,6-tris(oxidanyl)phenyl]methyl]-6-ethyl-5-methyl-4-oxidanyl-pyran-2-one'>A1JKW</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=FMN:FLAVIN+MONONUCLEOTIDE'>FMN</scene>, <scene name='pdbligand=ORO:OROTIC+ACID'>ORO</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=9s1i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9s1i OCA], [https://pdbe.org/9s1i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9s1i RCSB], [https://www.ebi.ac.uk/pdbsum/9s1i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9s1i ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
| + | [https://www.uniprot.org/uniprot/PYRD_HUMAN PYRD_HUMAN] Defects in DHODH are the cause of postaxial acrofacial dysostosis (POADS) [MIM:[https://omim.org/entry/263750 263750]; also known as Miller syndrome. POADS is characterized by severe micrognathia, cleft lip and/or palate, hypoplasia or aplasia of the posterior elements of the limbs, coloboma of the eyelids and supernumerary nipples. POADS is a very rare disorder: only 2 multiplex families, each consisting of 2 affected siblings born to unaffected, nonconsanguineous parents, have been described among a total of around 30 reported cases.<ref>PMID:19915526</ref> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/PYRD_HUMAN PYRD_HUMAN] Catalyzes the conversion of dihydroorotate to orotate with quinone as electron acceptor. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Human dihydroorotate dehydrogenase (hDHODH), catalyzing the rate-limiting step of the pyrimidine biosynthesis pathway (PBP), is a drug target extensively investigated for various diseases including cancer, autoimmune disorders, and viral infections. We present evidence that the heterodimeric phloroglucinylpyrone arzanol potently inhibits hDHODH by competing with ubiquinone for binding to the lipophilic patch (LP) of the enzyme. Co-crystallization experiments on the enzyme-arzanol complex provided further insights into the binding pocket of hDHODH, revealing detailed features that could inspire the design of innovative inhibitors. The cellular translation of these enzymatic and biochemical data was validated in antiviral assays on SARS-CoV-2 infected cells. Taken together, these results exemplify the potential of natural products to explore novel areas of the protein druggable space and provide information relevant to multiple critical areas of drug discovery. | ||
| - | + | Arzanol Inhibits Human Dihydroorotate Dehydrogenase and Shows Antiviral Activity.,Alberti M, Tamburello M, Salamone S, Gallinella G, Sanna C, Appendino GB, Lolli ML, Massarotti A, Pollastro F, Miggiano R J Nat Prod. 2025 Oct 27. doi: 10.1021/acs.jnatprod.5c00887. PMID:41143446<ref>PMID:41143446</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: | + | <div class="pdbe-citations 9s1i" style="background-color:#fffaf0;"></div> |
| - | [[Category: Alberti | + | == References == |
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Alberti M]] | ||
| + | [[Category: Miggiano R]] | ||
Current revision
Crystal structure of human Dihydroorotate Dehydrogenase in complex with arzanol
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