EzCatDB: S00218

DB codeS00218
CATH domainDomain 13.20.20.70Catalytic domain
E.C.1.3.5.2
CSA1d3g
MACiEM0109

CATH domainRelated DB codes (homologues)
3.20.20.70S00215,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
Swiss-protKEGG

Q02127
Protein nameDihydroorotate dehydrogenase, mitochondrialdihydroorotate dehydrogenase (quinone)
dihydroorotate:ubiquinone oxidoreductase
(S)-dihydroorotate:(acceptor) oxidoreductase
(S)-dihydroorotate:acceptor oxidoreductase
DHOdehase (ambiguous)
DHOD (ambiguous)
DHODase (ambiguous)
DHODH
SynonymsDHOdehase
EC 1.3.3.1
Dihydroorotate oxidase

KEGG pathways
MAP codePathways
MAP00240Pyrimidine metabolism

Swiss-prot:Accession NumberQ02127
Entry namePYRD_HUMAN
Activity(S)-dihydroorotate + a quinone = orotate + a quinol.
SubunitMonomer.
Subcellular locationMitochondrion inner membrane, Single-pass membrane protein.
CofactorBinds 1 FAD per subunit.


CofactorsSubstratesProducts
KEGG-idC00016C00061C00337C00472C00295C00530
CompoundFADFMN(S)-DihydroorotateQuinoneOrotateQuinol
Typeamide group,amine group,aromatic ring (only carbon atom),aromatic ring (with nitrogen atoms),carbohydrate,nucleotideamide group,amine group,aromatic ring (only carbon atom),aromatic ring (with nitrogen atoms),carbohydrate,phosphate group/phosphate ionamino acids,amide grouparomatic ring (only carbon atom)amide group,aromatic ring (with nitrogen atoms),carboxyl grouparomatic ring (only carbon atom)
1d3gAUnboundBound:FMNUnboundUnboundBound:OROUnbound
1d3hAUnboundBound:FMNUnboundUnboundBound:OROUnbound

Active-site residues
resource
literature [8]
pdbCatalytic residues
1d3gASER 215;LYS 255
1d3hASER 215;LYS 255

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[3]p.1141-1142, Fig.4
[8]p.30-31
[9]p.130-131
[10]


references
[1]
PubMed ID2996510
JournalBiochem Med
Year1985
Volume34
Pages60-9
AuthorsGero AM, O'Sullivan WJ, Brown DJ
TitleHuman spleen dihydroorotate dehydrogenase: a study of inhibition of the enzyme.
[2]
PubMed ID1765126
JournalExperientia
Year1991
Volume47
Pages1139-1148
AuthorsSuckling CJ
TitleMolecular recognition in applied enzyme chemistry.
[3]
PubMed ID7741767
JournalBiochem Pharmacol
Year1995
Volume49
Pages947-54
AuthorsCleaveland ES, Monks A, Vaigro-Wolff A, Zaharevitz DW, Paull K, Ardalan K, Cooney DA, Ford H Jr
TitleSite of action of two novel pyrimidine biosynthesis inhibitors accurately predicted by the compare program.
[4]
PubMed ID9313772
JournalBiochem Pharmacol
Year1997
Volume54
Pages459-65
AuthorsDavis JP, Copeland RA
TitleHistidine to alanine mutants of human dihydroorotate dehydrogenase. Identification of a brequinar-resistant mutant enzyme.
[5]
PubMed ID9873513
JournalBioorg Med Chem Lett
Year1998
Volume8
Pages2203-8
AuthorsAlbert R, Knecht H, Andersen E, Hungerford V, Schreier MH, Papageorgiou C
TitleIsoxazolylthioamides as potential immunosuppressants a combinatorial chemistry approach.
[6]
PubMed ID9871675
JournalBioorg Med Chem Lett
Year1998
Volume8
Pages307-12
AuthorsPitts 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
TitleStructure-activity relationships (SAR) of some tetracyclic heterocycles related to the immunosuppressive agent Brequinar Sodium.
[7]
PubMed ID10775458
JournalArch Biochem Biophys
Year2000
Volume377
Pages178-86
AuthorsMarcinkeviciene J, Jiang W, Locke G, Kopcho LM, Rogers MJ, Copeland RA
TitleA second dihydroorotate dehydrogenase (Type A) of the human pathogen Enterococcus faecalis: expression, purification, and steady-state kinetic mechanism.
[8]
CommentsX-ray crystallography
PubMed ID10673429
JournalStructure Fold Des
Year2000
Volume8
Pages25-33
AuthorsLiu S, Neidhardt EA, Grossman TH, Ocain T, Clardy J
TitleStructures of human dihydroorotate dehydrogenase in complex with antiproliferative agents.
Related PDB1d3g,1d3h
[9]
PubMed ID10694883
JournalTrends Biochem Sci
Year2000
Volume25
Pages126-32
AuthorsFraaije MW, Mattevi A
TitleFlavoenzymes: diverse catalysts with recurrent features.
[10]
PubMed ID11437361
JournalArch Biochem Biophys
Year2001
Volume391
Pages286-94
AuthorsBjornberg O, Jordan DB, Palfey BA, Jensen KF
TitleDihydrooxonate is a substrate of dihydroorotate dehydrogenase (DHOD) providing evidence for involvement of cysteine and serine residues in base catalysis.
[11]
PubMed ID12213251
JournalInsect Biochem Mol Biol
Year2002
Volume32
Pages1159-69
AuthorsLoffler M, Knecht W, Rawls J, Ullrich A, Dietz C
TitleDrosophila melanogaster dihydroorotate dehydrogenase: the N-terminus is important for biological function in vivo but not for catalytic properties in vitro.
[12]
PubMed ID12189151
JournalJ Biol Chem
Year2002
Volume277
Pages41827-34
AuthorsBaldwin J, Farajallah AM, Malmquist NA, Rathod PK, Phillips MA
TitleMalarial dihydroorotate dehydrogenase. Substrate and inhibitor specificity.
[13]
PubMed ID12361393
JournalJ Med Chem
Year2002
Volume45
Pages4669-78
AuthorsHaque 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
TitleParallel synthesis of potent, pyrazole-based inhibitors of Helicobacter pylori dihydroorotate dehydrogenase.

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):

createdupdated
2004-02-192012-10-02


Copyright: Nozomi Nagano, JST & CBRC-AIST
Funded by PRESTO/Japan Science and Technology Corporation (JST) (December 2001 - November 2004)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2006)
Funded by Grant-in-Aid for Scientific Research (B)/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (September 2005 - September 2010)
Funded by BIRD/Japan Science and Technology Corporation (JST) (October 2007 - September 2010)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2011 - March 2012)

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