EzCatDB: M00141
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DB codeM00141
CATH domainDomain 13.20.20.70 : TIM BarrelCatalytic domain
Domain 22.40.30.10 : Elongation Factor Tu (Ef-tu); domain 3Catalytic domain
Domain 33.40.50.80 : Rossmann fold
Domain 42.10.240.10 : Dihydroorotate dehydrogenase B (pyrk subunit); domain 3Catalytic domain
E.C.1.3.1.14

CATH domainRelated DB codes (homologues)
2.40.30.10 : Elongation Factor Tu (Ef-tu); domain 3D00043,M00006,M00159,M00164
3.20.20.70 : TIM BarrelS00215,S00217,S00218,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,T00015,T00239,D00664,D00665,D00804,D00863,T00089
3.40.50.80 : Rossmann foldD00043,M00006,M00159,M00164

Enzyme Name
UniProtKBKEGG

P54322P56968
Protein nameDihydroorotate dehydrogenase B, catalytic subunitDihydroorotate dehydrogenase electron transfer subunitdihydroorotate dehydrogenase (NAD+)
orotate reductase (NADH)
orotate reductase (NADH2)
DHOdehase (ambiguous)
DHOD (ambiguous)
DHODase (ambiguous)
dihydroorotate oxidase, pyrD (gene name)
SynonymsEC 1.3.3.1
Dihydroorotate oxidase B
DHOdehase B
DHODase B
DHOD B
None
RefSeqYP_001032420.1 (Protein)
NC_009004.1 (DNA/RNA sequence)
YP_001032419.1 (Protein)
NC_009004.1 (DNA/RNA sequence)
PfamPF01180 (DHO_dh)
[Graphical view]
PF10418 (DHODB_Fe-S_bind)
PF00970 (FAD_binding_6)
PF00175 (NAD_binding_1)
[Graphical view]

KEGG pathways
MAP codePathways
MAP00240Pyrimidine metabolism

UniProtKB:Accession NumberP54322P56968
Entry namePYRDB_LACLMPYRK_LACLM
Activity(S)-dihydroorotate + NAD(+) = orotate + NADH.
SubunitHeterotetramer of 2 PyrK and 2 PyrD type B subunits.Heterotetramer of 2 PyrK and 2 PyrD type B subunits.
Subcellular locationCytoplasm.Cytoplasm.
CofactorBinds 1 FMN per subunit.Binds 1 2Fe-2S cluster per subunit.,Binds 1 FAD per subunit.

Compound table: links to PDB-related databases & PoSSuM

CofactorsSubstratesProducts
KEGG-idC00016C00061L00023C00337C00003C00295C00004C00080
CompoundFADFMN[2Fe-2S](S)-DihydroorotateNAD+OrotateNADHH+
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 ionheavy metal,sulfide groupamino acids,amide groupamide group,amine group,nucleotideamide group,aromatic ring (with nitrogen atoms),carboxyl groupamide group,amine group,nucleotideothers
ChEBI16238
17621
33739
17025
15846
16742
16908
15378
PubChem643975
643976

439216
5893
967
439153
1038
                
1ep1AUnboundBound:FMNUnboundUnboundUnboundUnboundUnbound 
1ep2AUnboundBound:FMNUnboundUnboundUnboundBound:OROUnbound 
1ep3AUnboundBound:FMNUnboundUnboundUnboundUnboundUnbound 
1ep1B01Bound:FADUnboundUnboundUnboundUnboundUnboundUnbound 
1ep2B01Bound:FADUnboundUnboundUnboundUnboundUnboundUnbound 
1ep3B01Bound:FADUnboundUnboundUnboundUnboundUnboundUnbound 
1ep1B02UnboundUnboundUnboundUnboundUnboundUnboundUnbound 
1ep2B02UnboundUnboundUnboundUnboundUnboundUnboundUnbound 
1ep3B02UnboundUnboundUnboundUnboundUnboundUnboundUnbound 
1ep1B03UnboundUnboundBound:FESUnboundUnboundUnboundUnbound 
1ep2B03UnboundUnboundBound:FESUnboundUnboundUnboundUnbound 
1ep3B03UnboundUnboundBound:FESUnboundUnboundUnboundUnbound 

Active-site residues
resource
see D00029 (homologous enzyme data)
pdbCatalytic residuesCofactor-binding residues
          
1ep1ALYS 48;CYS 135
 
1ep2ALYS 48;CYS 135
 
1ep3ALYS 48;CYS 135
 
1ep1B01 
 
1ep2B01 
 
1ep3B01 
 
1ep1B02 
 
1ep2B02 
 
1ep3B02 
 
1ep1B03 
CYS 226;CYS 231;CYS 234;CYS 249(Iron-sulfur binding)
1ep2B03 
CYS 226;CYS 231;CYS 234;CYS 249(Iron-sulfur binding)
1ep3B03 
CYS 226;CYS 231;CYS 234;CYS 249(Iron-sulfur binding)

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[3]Scheme 1, p.13136
[8]Fig.1, p.1235

references
[1]
PubMed ID1765126
JournalExperientia
Year1991
Volume47
Pages1139-1148
AuthorsSuckling CJ
TitleMolecular recognition in applied enzyme chemistry.
[2]
CommentsCHARACTERIZATION
Medline ID97067197
PubMed ID8910599
JournalJ Biol Chem
Year1996
Volume271
Pages29359-65
AuthorsNielsen FS, Andersen PS, Jensen KF
TitleThe B form of dihydroorotate dehydrogenase from Lactococcus lactis consists of two different subunits, encoded by the pyrDb and pyrK genes, and contains FMN, FAD, and [FeS] redox centers.
Related UniProtKBP54322
[3]
PubMed ID10529184
JournalBiochemistry
Year1999
Volume38
Pages13129-37
AuthorsMarcinkeviciene J, Tinney LM, Wang KH, Rogers MJ, Copeland RA
TitleDihydroorotate dehydrogenase B of Enterococcus faecalis. Characterization and insights into chemical mechanism.
[4]
PubMed ID10771442
JournalActa Crystallogr D Biol Crystallogr
Year2000
Volume56
Pages659-61
AuthorsRowland P, Norager S, Jensen KF, Larsen S
TitleCrystallization and preliminary X-ray studies of membrane-associated Escherichia coli dihydroorotate dehydrogenase.
[5]
PubMed ID10871048
JournalArch Biochem Biophys
Year2000
Volume378
Pages84-92
AuthorsJordan DB, Bisaha JJ, Picollelli MA
TitleCatalytic properties of dihydroorotate dehydrogenase from Saccharomyces cerevisiae: studies on pH, alternate substrates, and inhibitors.
[6]
PubMed ID10956027
JournalBiochemistry
Year2000
Volume39
Pages10373-84
AuthorsArgyrou A, Washabaugh MW, Pickart CM
TitleDihydroorotate dehydrogenase from Clostridium oroticum is a class 1B enzyme and utilizes a concerted mechanism of catalysis.
[7]
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.
[8]
CommentsX-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS)
Medline ID21029084
PubMed ID11188687
JournalStructure Fold Des
Year2000
Volume8
Pages1227-38
AuthorsRowland P, Norager S, Jensen KF, Larsen S
TitleStructure of dihydroorotate dehydrogenase B: electron transfer between two flavin groups bridged by an iron-sulphur cluster.
Related PDB1ep1,1ep2,1ep3
Related UniProtKBP56968
[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.

comments
This enzyme belongs to the dihydroorotate oxidase family-1B, whilst a homolgous enzyme (D00029 in EzCatDB) is a member of the family-1A. Moreover, another homologous one from human (S00218 in EzCatDB) belongs to the family-2.
Although this enzyme is supposed to have O2 as a substrate and H2O2 as a product, it is not clear that they are involved in its catalytic reaction. Instead, NAD compounds are involved in the reaction as a electron acceptor (see [2], [8]).
Thus, this reaction catalyzes the following reactions:
(A) Hydride transfer from dihydroorotate to FMN, giving orotate and FMNH2:
(B) Electron transfer from FMNH2 to [Fe2-S2] cluster, giving FMN:
(C) Electron transfer from [Fe2-S2] cluster FAD, giving FADH2:
(D) Hydride transfer from FADH2 to NAD, giving FAD and NADH2:

createdupdated
2004-03-252012-10-02


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Funded by BIRD/Japan Science and Technology Corporation (JST) (October 2007 - September 2010)
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Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2012 - March 2013)
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