DB code: M00141

CATH domain 3.20.20.70 : TIM Barrel Catalytic domain
2.40.30.10 : Elongation Factor Tu (Ef-tu); domain 3 Catalytic domain
3.40.50.80 : Rossmann fold
2.10.240.10 : Dihydroorotate dehydrogenase B (pyrk subunit); domain 3 Catalytic domain
E.C. 1.3.1.14
CSA
M-CSA
MACiE

CATH domain Related DB codes (homologues)
2.40.30.10 : Elongation Factor Tu (Ef-tu); domain 3 D00043 M00006 M00159 M00164
3.20.20.70 : TIM Barrel S00215 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 fold D00043 M00006 M00159 M00164

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
P54322 Dihydroorotate dehydrogenase B (NAD(+)), catalytic subunit
DHOD B
DHODase B
DHOdehase B
EC 1.3.1.14
Dihydroorotate oxidase B
Orotate reductase (NADH)
YP_001032420.1 (Protein)
NC_009004.1 (DNA/RNA sequence)
PF01180 (DHO_dh)
[Graphical View]
P56968 Dihydroorotate dehydrogenase B (NAD(+)), electron transfer subunit
Dihydroorotate oxidase B, electron transfer subunit
YP_001032419.1 (Protein)
NC_009004.1 (DNA/RNA sequence)
PF10418 (DHODB_Fe-S_bind)
PF00970 (FAD_binding_6)
PF00175 (NAD_binding_1)
[Graphical View]

KEGG enzyme name
dihydroorotate dehydrogenase (NAD+)
orotate reductase (NADH)
orotate reductase (NADH2)
DHOdehase (ambiguous)
DHOD (ambiguous)
DHODase (ambiguous)
dihydroorotate oxidase, pyrD (gene name)

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P56968 PYRK_LACLM Heterotetramer of 2 PyrK and 2 PyrD type B subunits. Cytoplasm. Binds 1 2Fe-2S cluster per subunit. Binds 1 FAD per subunit.
P54322 PYRDB_LACLM (S)-dihydroorotate + NAD(+) = orotate + NADH. Heterotetramer of 2 PyrK and 2 PyrD type B subunits. Cytoplasm. Binds 1 FMN per subunit.

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

Compound table
Cofactors Substrates Products Intermediates
KEGG-id C00016 C00061 L00023 C00337 C00003 C00295 C00004 C00080
E.C.
Compound FAD FMN [2Fe-2S] (S)-Dihydroorotate NAD+ Orotate NADH H+
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 heavy metal,sulfide group amino acids,amide group amide group,amine group,nucleotide amide group,aromatic ring (with nitrogen atoms),carboxyl group amide group,amine group,nucleotide others
ChEBI 16238
17621
33739
17025
15846
16742
16908
15378
PubChem 643975
643976
439216
5893
967
439153
1038
1ep1A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Bound:FMN Unbound Unbound Unbound Unbound Unbound
1ep2A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Bound:FMN Unbound Unbound Unbound Bound:ORO Unbound
1ep3A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Bound:FMN Unbound Unbound Unbound Unbound Unbound
1ep1B01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:FAD Unbound Unbound Unbound Unbound Unbound Unbound
1ep2B01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:FAD Unbound Unbound Unbound Unbound Unbound Unbound
1ep3B01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:FAD Unbound Unbound Unbound Unbound Unbound Unbound
1ep1B02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1ep2B02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1ep3B02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1ep1B03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Bound:FES Unbound Unbound Unbound Unbound
1ep2B03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Bound:FES Unbound Unbound Unbound Unbound
1ep3B03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Bound:FES Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
see D00029 (homologous enzyme data)

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1ep1A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain LYS 48;CYS 135
1ep2A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain LYS 48;CYS 135
1ep3A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain LYS 48;CYS 135
1ep1B01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1ep2B01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1ep3B01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1ep1B02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1ep2B02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1ep3B02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1ep1B03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain CYS 226;CYS 231;CYS 234;CYS 249(Iron-sulfur binding)
1ep2B03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain CYS 226;CYS 231;CYS 234;CYS 249(Iron-sulfur binding)
1ep3B03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain CYS 226;CYS 231;CYS 234;CYS 249(Iron-sulfur binding)

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[3]
Scheme 1, p.13136
[8]
Fig.1, p.1235

References
[1]
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
[2]
Resource
Comments CHARACTERIZATION
Medline ID 97067197
PubMed ID 8910599
Journal J Biol Chem
Year 1996
Volume 271
Pages 29359-65
Authors Nielsen FS, Andersen PS, Jensen KF
Title The 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 PDB
Related UniProtKB P54322
[3]
Resource
Comments
Medline ID
PubMed ID 10529184
Journal Biochemistry
Year 1999
Volume 38
Pages 13129-37
Authors Marcinkeviciene J, Tinney LM, Wang KH, Rogers MJ, Copeland RA
Title Dihydroorotate dehydrogenase B of Enterococcus faecalis. Characterization and insights into chemical mechanism.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 10771442
Journal Acta Crystallogr D Biol Crystallogr
Year 2000
Volume 56
Pages 659-61
Authors Rowland P, Norager S, Jensen KF, Larsen S
Title Crystallization and preliminary X-ray studies of membrane-associated Escherichia coli dihydroorotate dehydrogenase.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 10871048
Journal Arch Biochem Biophys
Year 2000
Volume 378
Pages 84-92
Authors Jordan DB, Bisaha JJ, Picollelli MA
Title Catalytic properties of dihydroorotate dehydrogenase from Saccharomyces cerevisiae: studies on pH, alternate substrates, and inhibitors.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 10956027
Journal Biochemistry
Year 2000
Volume 39
Pages 10373-84
Authors Argyrou A, Washabaugh MW, Pickart CM
Title Dihydroorotate dehydrogenase from Clostridium oroticum is a class 1B enzyme and utilizes a concerted mechanism of catalysis.
Related PDB
Related UniProtKB
[7]
Resource
Comments
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
Related UniProtKB
[8]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS)
Medline ID 21029084
PubMed ID 11188687
Journal Structure Fold Des
Year 2000
Volume 8
Pages 1227-38
Authors Rowland P, Norager S, Jensen KF, Larsen S
Title Structure of dihydroorotate dehydrogenase B: electron transfer between two flavin groups bridged by an iron-sulphur cluster.
Related PDB 1ep1 1ep2 1ep3
Related UniProtKB P56968
[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

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:

Created Updated
2004-03-25 2012-10-02