2WV8
Complex of human dihydroorotate dehydrogenase with the inhibitor 221290
Summary for 2WV8
| Entry DOI | 10.2210/pdb2wv8/pdb |
| Related | 1D3G 1D3H 2B0M 2BXV |
| Descriptor | DIHYDROOROTATE DEHYDROGENASE, MITOCHONDRIAL, FLAVIN MONONUCLEOTIDE, OROTIC ACID, ... (8 entities in total) |
| Functional Keywords | flavoprotein, transmembrane, mitochondrion inner membrane, oxidoreductase, transit peptide, enzyme inhibition, pyrimidine biosynthesis, structure-based drug design, inflamation |
| Biological source | HOMO SAPIENS (HUMAN) |
| Cellular location | Mitochondrion inner membrane ; Single-pass membrane protein : Q02127 |
| Total number of polymer chains | 1 |
| Total formula weight | 40954.53 |
| Authors | Walse, B.,Svensson, B.,Fritzson, I.,Dahlberg, L.,Wellmar, U.,Al-Karadaghi, S. (deposition date: 2009-10-15, release date: 2010-08-25, Last modification date: 2024-05-08) |
| Primary citation | Fritzson, I.,Svensson, B.,Al-Karadaghi, S.,Walse, B.,Wellmar, U.,Nilsson, U.J.,Da Graca Thrige, D.,Jonsson, S. Inhibition of Human Dhodh by 4-Hydroxycoumarins, Fenamic Acids, and N-(Alkylcarbonyl)Anthranilic Acids Identified by Structure-Guided Fragment Selection. Chemmedchem, 5:608-, 2010 Cited by PubMed Abstract: A strategy that combines virtual screening and structure-guided selection of fragments was used to identify three unexplored classes of human DHODH inhibitor compounds: 4-hydroxycoumarins, fenamic acids, and N-(alkylcarbonyl)anthranilic acids. Structure-guided selection of fragments targeting the inner subsite of the DHODH ubiquinone binding site made these findings possible with screening of fewer than 300 fragments in a DHODH assay. Fragments from the three inhibitor classes identified were subsequently chemically expanded to target an additional subsite of hydrophobic character. All three classes were found to exhibit distinct structure-activity relationships upon expansion. The novel N-(alkylcarbonyl)anthranilic acid class shows the most promising potency against human DHODH, with IC(50) values in the low nanomolar range. The structure of human DHODH in complex with an inhibitor of this class is presented. PubMed: 20183850DOI: 10.1002/CMDC.200900454 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.9 Å) |
Structure validation
Download full validation report
