4IGH
High resolution crystal structure of human dihydroorotate dehydrogenase bound with 4-quinoline carboxylic acid analog
Summary for 4IGH
| Entry DOI | 10.2210/pdb4igh/pdb |
| Descriptor | Dihydroorotate dehydrogenase (quinone), mitochondrial, FLAVIN MONONUCLEOTIDE, OROTIC ACID, ... (7 entities in total) |
| Functional Keywords | anti-viral, quinoline-4-carboxylic acid, redox, dehydrogenase, fmn, membrane, oxidoreductase-oxidoreductase inhibitor complex, oxidoreductase/oxidoreductase inhibitor |
| Biological source | Homo sapiens (human) |
| Cellular location | Mitochondrion inner membrane; Single-pass membrane protein: Q02127 |
| Total number of polymer chains | 1 |
| Total formula weight | 42143.88 |
| Authors | Deng, X.,Das, P.,Fontoura, B.M.A.,Phillips, M.A.,De Brabander, J.K. (deposition date: 2012-12-17, release date: 2013-08-21, Last modification date: 2023-09-20) |
| Primary citation | Das, P.,Deng, X.,Zhang, L.,Roth, M.G.,Fontoura, B.M.,Phillips, M.A.,De Brabander, J.K. SAR Based Optimization of a 4-Quinoline Carboxylic Acid Analog with Potent Anti-Viral Activity. ACS MED.CHEM.LETT., 4:517-521, 2013 Cited by PubMed Abstract: It is established that drugs targeting viral proteins are at risk of generating resistant strains. However, drugs targeting host factors can potentially avoid this problem. Herein we report structure-activity relationship studies leading to the discovery of a very potent lead compound 6-fluoro-2-(5-isopropyl-2-methyl-4-phenoxyphenyl)quinoline-4-carboxylic acid () that inhibits human dihydroorotate dehydrogenase (DHODH) with an IC of 1 nM, and viral replication of VSV and WSN-Influenza with an EC of 2 nM and 41 nM. We also solved the X-ray structure of human DHODH bound to , providing structural insight into the potent inhibition of biaryl ether analogs of brequinar. PubMed: 23930152DOI: 10.1021/ml300464h PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.3 Å) |
Structure validation
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