DB code: D00029

CATH domain 3.20.20.70 : TIM Barrel Catalytic domain
2.30.26.10 : Dihydroorotate Dehydrogenase A; chain A, domain 2
E.C. 1.3.98.1
CSA 2dor
M-CSA 2dor
MACiE

CATH domain Related DB codes (homologues)
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 M00141 T00015 T00239 D00664 D00665 D00804 D00863 T00089

Uniprot Enzyme Name
UniprotKB Protein name Synonyms Pfam
Q53ZE5 Dihydroorotate dehydrogenase A
EC 1.3.3.1
Dihydroorotate oxidase A
DHOdehase A
DHODase A
DHOD A
PF01180 (DHO_dh)
[Graphical View]

KEGG enzyme name
dihydroorotate dehydrogenase (fumarate)
DHOdehase (ambiguous)
dihydroorotate dehydrogenase (ambiguous)
dihydoorotic acid dehydrogenase (ambiguous)
DHOD (ambiguous)
DHODase (ambiguous)
dihydroorotate oxidase, pyr4 (gene name)

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
Q53ZE5 PYRDA_LACLC (S)-dihydroorotate + fumarate = orotate + succinate. Homodimer (By similarity). Cytoplasm (By similarity). Binds 1 FMN per subunit (By similarity).

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

Compound table
Cofactors Substrates Products Intermediates
KEGG-id C00061 C00337 C00122 C00295 C00042
E.C.
Compound FMN (S)-Dihydroorotate Fumarate Orotate Succinate
Type amide group,amine group,aromatic ring (only carbon atom),aromatic ring (with nitrogen atoms),carbohydrate,phosphate group/phosphate ion amino acids,amide group carboxyl group amide group,aromatic ring (with nitrogen atoms),carboxyl group carboxyl group
ChEBI 17621
 17621
 		17025
 17025
 		18012
 18012
 		16742
 16742
 		15741
 15741
PubChem 643976
 643976
 		439216
 439216
 		21883788
 444972
 21883788
 444972
 		967
 967
 		1110
 21952380
 1110
 21952380
1dorA01 Bound:FMN Unbound Unbound Unbound Unbound
1dorB01 Bound:FMN Unbound Unbound Unbound Unbound
1jqvA01 Bound:FMN Unbound Unbound Bound:ORO Unbound
1jqvB01 Bound:FMN Unbound Unbound Bound:ORO Unbound
1jqxA01 Bound:FMN Unbound Unbound Bound:ORO Unbound
1jqxB01 Bound:FMN Unbound Unbound Bound:ORO Unbound
1jrbA01 Bound:FMN Unbound Unbound Bound:ORO Unbound
1jrbB01 Bound:FMN Unbound Unbound Bound:ORO Unbound
1jrcA01 Bound:FMN Unbound Unbound Bound:ORO Unbound
1jrcB01 Bound:FMN Unbound Unbound Bound:ORO Unbound
1jubA01 Bound:FMN Unbound Unbound Unbound Unbound
1jubB01 Bound:FMN Unbound Unbound Unbound Unbound
1jueA01 Bound:FMN Unbound Unbound Unbound Unbound
1jueB01 Bound:FMN Unbound Unbound Unbound Unbound
1ovdA01 Bound:FMN Unbound Unbound Bound:ORO Unbound
1ovdB01 Bound:FMN Unbound Unbound Bound:ORO Unbound
2dorA01 Bound:FMN Unbound Unbound Bound:ORO Unbound
2dorB01 Bound:FMN Unbound Unbound Bound:ORO Unbound
1dorA02 Unbound Unbound Unbound Unbound Unbound
1dorB02 Unbound Unbound Unbound Unbound Unbound
1jqvA02 Unbound Unbound Unbound Unbound Unbound
1jqvB02 Unbound Unbound Unbound Unbound Unbound
1jqxA02 Unbound Unbound Unbound Unbound Unbound
1jqxB02 Unbound Unbound Unbound Unbound Unbound
1jrbA02 Unbound Unbound Unbound Unbound Unbound
1jrbB02 Unbound Unbound Unbound Unbound Unbound
1jrcA02 Unbound Unbound Unbound Unbound Unbound
1jrcB02 Unbound Unbound Unbound Unbound Unbound
1jubA02 Unbound Unbound Unbound Unbound Unbound
1jubB02 Unbound Unbound Unbound Unbound Unbound
1jueA02 Unbound Unbound Unbound Unbound Unbound
1jueB02 Unbound Unbound Unbound Unbound Unbound
1ovdA02 Unbound Unbound Unbound Unbound Unbound
1ovdB02 Unbound Unbound Unbound Unbound Unbound
2dorA02 Unbound Unbound Unbound Unbound Unbound
2dorB02 Unbound Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
literature [3], [5], [11]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1dorA01 LYS 43;CYS 130
1dorB01 LYS 43;CYS 130
1jqvA01 LYS 43;CYS 130
1jqvB01 LYS 43;CYS 130
1jqxA01 LYS 43;CYS 130
1jqxB01 LYS 43;CYS 130
1jrbA01 LYS 43;CYS 130
1jrbB01 LYS 43;CYS 130
1jrcA01 LYS 43;CYS 130
1jrcB01 LYS 43;CYS 130
1jubA01 LYS 43;CYS 130 mutant K136E
1jubB01 LYS 43;CYS 130 mutant K136E
1jueA01 LYS 43;CYS 130
1jueB01 LYS 43;CYS 130
1ovdA01 LYS 43;CYS 130 mutant K136E
1ovdB01 LYS 43;CYS 130 mutant K136E
2dorA01 LYS 43;CYS 130
2dorB01 LYS 43;CYS 130
1dorA02
1dorB02
1jqvA02 mutant K213E
1jqvB02 mutant K213E
1jqxA02 mutant R57A
1jqxB02 mutant R57A
1jrbA02 mutant P56A
1jrbB02 mutant P56A
1jrcA02 mutant N67A
1jrcB02 mutant N67A
1jubA02
1jubB02
1jueA02
1jueB02
1ovdA02
1ovdB02
2dorA02
2dorB02

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[4]
p.248-249
[5]
p.1275-1277
[7]
p.2906-2908
[8]
[10]
Fig.1, Fig.4, p.130-131
[11]
[12]
p.4387-4389
[14]

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
Medline ID
PubMed ID 8732756
Journal Protein Sci
Year 1996
Volume 5
Pages 852-6
Authors Nielsen FS, Rowland P, Larsen S, Jensen KF
Title Purification and characterization of dihydroorotate dehydrogenase A from Lactococcus lactis, crystallization and preliminary X-ray diffraction studies of the enzyme.
Related PDB
Related UniProtKB
[3]
Resource
Comments MUTAGENESIS OF LYS-43; CYS-130; ASN-132 AND LYS-164
Medline ID 98070244
PubMed ID 9405053
Journal Biochemistry
Year 1997
Volume 36
Pages 16197-205
Authors Bjornberg O, Rowland P, Larsen S, Jensen KF
Title Active site of dihydroorotate dehydrogenase A from Lactococcus lactis investigated by chemical modification and mutagenesis.
Related PDB
Related UniProtKB P54321
[4]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS)
Medline ID 97184689
PubMed ID 9032071
Journal Structure
Year 1997
Volume 5
Pages 239-52
Authors Rowland P, Nielsen FS, Jensen KF, Larsen S
Title The crystal structure of the flavin containing enzyme dihydroorotate dehydrogenase A from Lactococcus lactis.
Related PDB 1dor
Related UniProtKB P54321
[5]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS)
Medline ID 98318035
PubMed ID 9655329
Journal Protein Sci
Year 1998
Volume 7
Pages 1269-79
Authors Rowland P, Bjornberg O, Nielsen FS, Jensen KF, Larsen S
Title The crystal structure of Lactococcus lactis dihydroorotate dehydrogenase A complexed with the enzyme reaction product throws light on its enzymatic function.
Related PDB 2dor
Related UniProtKB P54321
[6]
Resource
Comments
Medline ID
PubMed ID 10545205
Journal Arch Biochem Biophys
Year 1999
Volume 371
Pages 191-201
Authors Kahler AE, Nielsen FS, Switzer RL
Title Biochemical characterization of the heteromeric Bacillus subtilis dihydroorotate dehydrogenase and its isolated subunits.
Related PDB
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 10074342
Journal Biochemistry
Year 1999
Volume 38
Pages 2899-908
Authors Bjornberg O, Gruner AC, Roepstorff P, Jensen KF
Title The activity of Escherichia coli dihydroorotate dehydrogenase is dependent on a conserved loop identified by sequence homology, mutagenesis, and limited proteolysis.
Related PDB
Related UniProtKB
[8]
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
[9]
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
[10]
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
[11]
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
[12]
Resource
Comments
Medline ID
PubMed ID 11284694
Journal Biochemistry
Year 2001
Volume 40
Pages 4381-90
Authors Palfey BA, Bjornberg O, Jensen KF
Title Insight into the chemistry of flavin reduction and oxidation in Escherichia coli dihydroorotate dehydrogenase obtained by rapid reaction studies.
Related PDB
Related UniProtKB
[13]
Resource
Comments
Medline ID
PubMed ID 12381841
Journal Protein Sci
Year 2002
Volume 11
Pages 2575-83
Authors Ottosen MB, Bjornberg O, Norager S, Larsen S, Palfey BA, Jensen KF
Title The dimeric dihydroorotate dehydrogenase A from Lactococcus lactis dissociates reversibly into inactive monomers.
Related PDB
Related UniProtKB
[14]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 12732650
Journal J Biol Chem
Year 2003
Volume 278
Pages 28812-22
Authors Norager S, Arent S, Bjornberg O, Ottosen M, Lo Leggio L, Jensen KF, Larsen S
Title Lactococcus lactis dihydroorotate dehydrogenase A mutants reveal important facets of the enzymatic function.
Related PDB 1jqv 1jqx 1jrb 1jrc 1jub 1jue 1ovd
Related UniProtKB

Comments
According to the literature [2], this enzyme belongs to the dihydroorotate oxidase family-1A, whilst a homolgous enzyme (M00141 in EzCatDB) is a member of the family-1B. Moreover, another homologous one from human (S00218 in EzCatDB) belongs to the family-2.
This enzyme catalyzes the following reactions (see [7], [8], [12]):
(A) Hydride transfer from dihydroorotate to FMN, giving orotate and FMNH2(reduced form):
(B) Hydride transfer from FMNH2 to O2, giving FMN and H2O2:

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