DB code: S00218

CATH domain 3.20.20.70 : TIM Barrel Catalytic domain
E.C. 1.3.5.2
CSA 1d3g
M-CSA 1d3g
MACiE M0109

CATH domain Related DB codes (homologues)
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

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
Q02127 Dihydroorotate dehydrogenase (quinone), mitochondrial
DHOdehase
EC 1.3.5.2
Dihydroorotate oxidase
NP_001352.2 (Protein)
NM_001361.4 (DNA/RNA sequence)
PF01180 (DHO_dh)
[Graphical View]

KEGG enzyme name
dihydroorotate dehydrogenase (quinone)
dihydroorotate:ubiquinone oxidoreductase
(S)-dihydroorotate:(acceptor) oxidoreductase
(S)-dihydroorotate:acceptor oxidoreductase
DHOdehase (ambiguous)
DHOD (ambiguous)
DHODase (ambiguous)
DHODH

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
Q02127 PYRD_HUMAN (S)-dihydroorotate + a quinone = orotate + a quinol. Monomer. Mitochondrion inner membrane, Single-pass membrane protein. Binds 1 FAD per subunit.

KEGG Pathways
Map code Pathways E.C.
MAP00240 Pyrimidine metabolism

Compound table
Cofactors Substrates Products Intermediates
KEGG-id C00016 C00061 C00337 C00472 C00295 C00530
E.C.
Compound FAD FMN (S)-Dihydroorotate Quinone Orotate Quinol
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)
ChEBI 16238
17621
17025
16509
16742
17594
PubChem 643975
643976
439216
4650
967
785
1d3gA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Bound:FMN Unbound Unbound Bound:ORO Unbound
1d3hA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Bound:FMN Unbound Unbound Bound:ORO Unbound

Reference for Active-site residues
resource references E.C.
literature [8]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1d3gA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 215;LYS 255
1d3hA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 215;LYS 255

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[3]
p.1141-1142, Fig.4
[8]
p.30-31
[9]
p.130-131
[10]

References
[1]
Resource
Comments
Medline ID
PubMed ID 2996510
Journal Biochem Med
Year 1985
Volume 34
Pages 60-9
Authors Gero AM, O'Sullivan WJ, Brown DJ
Title Human spleen dihydroorotate dehydrogenase: a study of inhibition of the enzyme.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 1765126
Journal Experientia
Year 1991
Volume 47
Pages 1139-1148
Authors Suckling CJ
Title Molecular recognition in applied enzyme chemistry.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 7741767
Journal Biochem Pharmacol
Year 1995
Volume 49
Pages 947-54
Authors Cleaveland ES, Monks A, Vaigro-Wolff A, Zaharevitz DW, Paull K, Ardalan K, Cooney DA, Ford H Jr
Title Site of action of two novel pyrimidine biosynthesis inhibitors accurately predicted by the compare program.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 9313772
Journal Biochem Pharmacol
Year 1997
Volume 54
Pages 459-65
Authors Davis JP, Copeland RA
Title Histidine to alanine mutants of human dihydroorotate dehydrogenase. Identification of a brequinar-resistant mutant enzyme.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 9873513
Journal Bioorg Med Chem Lett
Year 1998
Volume 8
Pages 2203-8
Authors Albert R, Knecht H, Andersen E, Hungerford V, Schreier MH, Papageorgiou C
Title Isoxazolylthioamides as potential immunosuppressants a combinatorial chemistry approach.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 9871675
Journal Bioorg Med Chem Lett
Year 1998
Volume 8
Pages 307-12
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
Title Structure-activity relationships (SAR) of some tetracyclic heterocycles related to the immunosuppressive agent Brequinar Sodium.
Related PDB
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 10775458
Journal Arch Biochem Biophys
Year 2000
Volume 377
Pages 178-86
Authors Marcinkeviciene J, Jiang W, Locke G, Kopcho LM, Rogers MJ, Copeland RA
Title A second dihydroorotate dehydrogenase (Type A) of the human pathogen Enterococcus faecalis: expression, purification, and steady-state kinetic mechanism.
Related PDB
Related UniProtKB
[8]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 10673429
Journal Structure Fold Des
Year 2000
Volume 8
Pages 25-33
Authors Liu S, Neidhardt EA, Grossman TH, Ocain T, Clardy J
Title Structures of human dihydroorotate dehydrogenase in complex with antiproliferative agents.
Related PDB 1d3g 1d3h
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID 10694883
Journal Trends Biochem Sci
Year 2000
Volume 25
Pages 126-32
Authors Fraaije MW, Mattevi A
Title Flavoenzymes: diverse catalysts with recurrent features.
Related PDB
Related UniProtKB
[10]
Resource
Comments
Medline ID
PubMed ID 11437361
Journal Arch Biochem Biophys
Year 2001
Volume 391
Pages 286-94
Authors Bjornberg O, Jordan DB, Palfey BA, Jensen KF
Title Dihydrooxonate is a substrate of dihydroorotate dehydrogenase (DHOD) providing evidence for involvement of cysteine and serine residues in base catalysis.
Related PDB
Related UniProtKB
[11]
Resource
Comments
Medline ID
PubMed ID 12213251
Journal Insect Biochem Mol Biol
Year 2002
Volume 32
Pages 1159-69
Authors Loffler M, Knecht W, Rawls J, Ullrich A, Dietz C
Title Drosophila melanogaster dihydroorotate dehydrogenase: the N-terminus is important for biological function in vivo but not for catalytic properties in vitro.
Related PDB
Related UniProtKB
[12]
Resource
Comments
Medline ID
PubMed ID 12189151
Journal J Biol Chem
Year 2002
Volume 277
Pages 41827-34
Authors Baldwin J, Farajallah AM, Malmquist NA, Rathod PK, Phillips MA
Title Malarial dihydroorotate dehydrogenase. Substrate and inhibitor specificity.
Related PDB
Related UniProtKB
[13]
Resource
Comments
Medline ID
PubMed ID 12361393
Journal J Med Chem
Year 2002
Volume 45
Pages 4669-78
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
Title Parallel synthesis of potent, pyrazole-based inhibitors of Helicobacter pylori dihydroorotate dehydrogenase.
Related PDB
Related UniProtKB

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):

Created Updated
2004-02-19 2012-10-02