9S1I
Crystal structure of human Dihydroorotate Dehydrogenase in complex with arzanol
This is a non-PDB format compatible entry.
Summary for 9S1I
| Entry DOI | 10.2210/pdb9s1i/pdb |
| Descriptor | Dihydroorotate dehydrogenase (quinone), mitochondrial, FLAVIN MONONUCLEOTIDE, OROTIC ACID, ... (7 entities in total) |
| Functional Keywords | pyrimidine biosynthesis, flavoprotein, dhodh, arzanol, oxidoreductase |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 43902.46 |
| Authors | |
| Primary citation | Alberti, M.,Tamburello, M.,Salamone, S.,Gallinella, G.,Sanna, C.,Appendino, G.B.,Lolli, M.L.,Massarotti, A.,Pollastro, F.,Miggiano, R. Arzanol Inhibits Human Dihydroorotate Dehydrogenase and Shows Antiviral Activity. J.Nat.Prod., 2025 Cited by PubMed Abstract: Human dihydroorotate dehydrogenase (DHODH), 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 DHODH by competing with ubiquinone for binding to the (LP) of the enzyme. Co-crystallization experiments on the enzyme-arzanol complex provided further insights into the binding pocket of DHODH, 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. PubMed: 41143446DOI: 10.1021/acs.jnatprod.5c00887 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.61 Å) |
Structure validation
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