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CATH domain | Related DB codes (homologues) |
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3.20.20.70 : TIM Barrel | S00215,S00217,S00219,S00532,S00198,S00220,S00745,S00537,S00538,S00539,S00826,S00841,S00235,S00239,S00240,S00243,S00244,S00199,S00200,S00201,S00221,S00222,S00847,S00224,S00225,S00226,D00014,D00029,M00141,T00015,T00239,D00664,D00665,D00804,D00863,T00089 |
Enzyme Name | UniProtKB | KEGG |
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| Q02127 |
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Protein name | Dihydroorotate dehydrogenase (quinone), mitochondrial | dihydroorotate dehydrogenase (quinone)dihydroorotate:ubiquinone oxidoreductase(S)-dihydroorotate:(acceptor) oxidoreductase(S)-dihydroorotate:acceptor oxidoreductaseDHOdehase (ambiguous)DHOD (ambiguous)DHODase (ambiguous)DHODH |
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Synonyms | DHOdehaseEC 1.3.5.2Dihydroorotate oxidase |
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RefSeq | NP_001352.2 (Protein) NM_001361.4 (DNA/RNA sequence)
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Pfam | PF01180 (DHO_dh) [Graphical view]
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KEGG pathways | MAP code | Pathways |
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MAP00240 | Pyrimidine metabolism |
UniProtKB:Accession Number | Q02127 |
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Entry name | PYRD_HUMAN |
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Activity | (S)-dihydroorotate + a quinone = orotate + a quinol. |
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Subunit | Monomer. |
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Subcellular location | Mitochondrion inner membrane, Single-pass membrane protein. |
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Cofactor | Binds 1 FAD per subunit. |
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Compound table: links to PDB-related databases & PoSSuM |
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| Cofactors | Substrates | Products |
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KEGG-id | C00016 | C00061 | C00337 | C00472 | C00295 | C00530 |
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Compound | FAD | FMN | (S)-Dihydroorotate | Quinone | Orotate | Quinol |
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Type | amide group,amine group,aromatic ring (only carbon atom),aromatic ring (with nitrogen atoms),carbohydrate,nucleotide | amide group,amine group,aromatic ring (only carbon atom),aromatic ring (with nitrogen atoms),carbohydrate,phosphate group/phosphate ion | amino acids,amide group | aromatic ring (only carbon atom) | amide group,aromatic ring (with nitrogen atoms),carboxyl group | aromatic ring (only carbon atom) |
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ChEBI | 16238
| 17621
| 17025
| 16509
| 16742
| 17594
|
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PubChem | 643975
| 643976
| 439216
| 4650
| 967
| 785
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| | | | | | | | | | | | | |
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1d3gA |  |  |  |  |  |  |  | Unbound | Bound:FMN | Unbound | Unbound | Bound:ORO | Unbound |
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1d3hA |  |  |  |  |  |  |  | Unbound | Bound:FMN | Unbound | Unbound | Bound:ORO | Unbound |
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References for Catalytic Mechanism | References | Sections | No. of steps in catalysis |
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[3] | p.1141-1142, Fig.4 |
| [8] | p.30-31 |
| [9] | p.130-131 |
| [10] |
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references | [1] |
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PubMed ID | 2996510 |
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Journal | Biochem Med |
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Year | 1985 |
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Volume | 34 |
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Pages | 60-9 |
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Authors | Gero AM, O'Sullivan WJ, Brown DJ |
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Title | Human spleen dihydroorotate dehydrogenase: a study of inhibition of the enzyme. |
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[2] |
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PubMed ID | 1765126 |
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Journal | Experientia |
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Year | 1991 |
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Volume | 47 |
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Pages | 1139-1148 |
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Authors | Suckling CJ |
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Title | Molecular recognition in applied enzyme chemistry. |
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[3] |
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PubMed ID | 7741767 |
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Journal | Biochem Pharmacol |
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Year | 1995 |
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Volume | 49 |
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Pages | 947-54 |
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Authors | Cleaveland ES, Monks A, Vaigro-Wolff A, Zaharevitz DW, Paull K, Ardalan K, Cooney DA, Ford H Jr |
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Title | Site of action of two novel pyrimidine biosynthesis inhibitors accurately predicted by the compare program. |
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[4] |
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PubMed ID | 9313772 |
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Journal | Biochem Pharmacol |
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Year | 1997 |
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Volume | 54 |
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Pages | 459-65 |
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Authors | Davis JP, Copeland RA |
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Title | Histidine to alanine mutants of human dihydroorotate dehydrogenase. Identification of a brequinar-resistant mutant enzyme. |
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[5] |
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PubMed ID | 9873513 |
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Journal | Bioorg Med Chem Lett |
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Year | 1998 |
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Volume | 8 |
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Pages | 2203-8 |
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Authors | Albert R, Knecht H, Andersen E, Hungerford V, Schreier MH, Papageorgiou C |
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Title | Isoxazolylthioamides as potential immunosuppressants a combinatorial chemistry approach. |
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[6] |
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PubMed ID | 9871675 |
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Journal | Bioorg Med Chem Lett |
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Year | 1998 |
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Volume | 8 |
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Pages | 307-12 |
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Authors | Pitts WJ, Jetter JW, Pinto DJ, Orwat MJ, Batt DG, Sherk SR, Petraitis JJ, Jacobson IC, Copeland RA, Dowling RL, Jaffee BD, Gardner TL, Jones EA, Magolda RL |
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Title | Structure-activity relationships (SAR) of some tetracyclic heterocycles related to the immunosuppressive agent Brequinar Sodium. |
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[7] |
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PubMed ID | 10775458 |
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Journal | Arch Biochem Biophys |
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Year | 2000 |
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Volume | 377 |
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Pages | 178-86 |
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Authors | Marcinkeviciene J, Jiang W, Locke G, Kopcho LM, Rogers MJ, Copeland RA |
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Title | A second dihydroorotate dehydrogenase (Type A) of the human pathogen Enterococcus faecalis: expression, purification, and steady-state kinetic mechanism. |
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[8] |
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Comments | X-ray crystallography |
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PubMed ID | 10673429 |
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Journal | Structure Fold Des |
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Year | 2000 |
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Volume | 8 |
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Pages | 25-33 |
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Authors | Liu S, Neidhardt EA, Grossman TH, Ocain T, Clardy J |
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Title | Structures of human dihydroorotate dehydrogenase in complex with antiproliferative agents. |
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Related PDB | 1d3g,1d3h |
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[9] |
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PubMed ID | 10694883 |
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Journal | Trends Biochem Sci |
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Year | 2000 |
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Volume | 25 |
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Pages | 126-32 |
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Authors | Fraaije MW, Mattevi A |
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Title | Flavoenzymes: diverse catalysts with recurrent features. |
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[10] |
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PubMed ID | 11437361 |
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Journal | Arch Biochem Biophys |
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Year | 2001 |
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Volume | 391 |
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Pages | 286-94 |
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Authors | Bjornberg O, Jordan DB, Palfey BA, Jensen KF |
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Title | Dihydrooxonate is a substrate of dihydroorotate dehydrogenase (DHOD) providing evidence for involvement of cysteine and serine residues in base catalysis. |
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[11] |
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PubMed ID | 12213251 |
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Journal | Insect Biochem Mol Biol |
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Year | 2002 |
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Volume | 32 |
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Pages | 1159-69 |
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Authors | Loffler M, Knecht W, Rawls J, Ullrich A, Dietz C |
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Title | Drosophila melanogaster dihydroorotate dehydrogenase: the N-terminus is important for biological function in vivo but not for catalytic properties in vitro. |
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[12] |
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PubMed ID | 12189151 |
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Journal | J Biol Chem |
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Year | 2002 |
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Volume | 277 |
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Pages | 41827-34 |
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Authors | Baldwin J, Farajallah AM, Malmquist NA, Rathod PK, Phillips MA |
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Title | Malarial dihydroorotate dehydrogenase. Substrate and inhibitor specificity. |
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[13] |
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PubMed ID | 12361393 |
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Journal | J Med Chem |
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Year | 2002 |
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Volume | 45 |
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Pages | 4669-78 |
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Authors | Haque TS, Tadesse S, Marcinkeviciene J, Rogers MJ, Sizemore C, Kopcho LM, Amsler K, Ecret LD, Zhan DL, Hobbs F, Slee A, Trainor GL, Stern AM, Copeland RA, Combs AP |
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Title | Parallel synthesis of potent, pyrazole-based inhibitors of Helicobacter pylori dihydroorotate dehydrogenase. |
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comments | This enzyme belongs to the dihydroorotate oxidase family-2. Whilst a homolgous enzyme (M00141 in EzCatDB) is a member of the family-1B, another homologous one (D00029 in EzCatDB) belongs to the family-1A. According to the literature [8], this enzyme catalyzes the following reactions: (A) Hydride transfer from dihydroorotate to FMN, giving orotate and FMNH2: (B) Hydride transfer from FMNH2 to quinone(or ubiquinone;Q), giving FMN and hydroquinone(or ubiquinol;QH2):
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created | updated |
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2004-02-19 | 2012-10-02 |
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