EzCatDB: D00029

DB codeD00029
CATH domainDomain 13.20.20.70Catalytic domain
Domain 22.30.26.10
E.C.1.3.98.1
CSA2dor

CATH domainRelated DB codes (homologues)
3.20.20.70S00215,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

Enzyme Name
Swiss-protKEGG

Q53ZE5
Protein nameDihydroorotate dehydrogenase Adihydroorotate dehydrogenase (fumarate)
DHOdehase (ambiguous)
dihydroorotate dehydrogenase (ambiguous)
dihydoorotic acid dehydrogenase (ambiguous)
DHOD (ambiguous)
DHODase (ambiguous)
dihydroorotate oxidase, pyr4 (gene name)
SynonymsEC 1.3.3.1
Dihydroorotate oxidase A
DHOdehase A
DHODase A
DHOD A

KEGG pathways
MAP codePathways
MAP00240Pyrimidine metabolism

Swiss-prot:Accession NumberQ53ZE5
Entry namePYRDA_LACLC
Activity(S)-dihydroorotate + fumarate = orotate + succinate.
SubunitHomodimer (By similarity).
Subcellular locationCytoplasm (By similarity).
CofactorBinds 1 FMN per subunit (By similarity).


CofactorsSubstratesProducts
KEGG-idC00061C00337C00122C00295C00042
CompoundFMN(S)-DihydroorotateFumarateOrotateSuccinate
Typeamide group,amine group,aromatic ring (only carbon atom),aromatic ring (with nitrogen atoms),carbohydrate,phosphate group/phosphate ionamino acids,amide groupcarboxyl groupamide group,aromatic ring (with nitrogen atoms),carboxyl groupcarboxyl group
1dorA01Bound:FMNUnboundUnboundUnboundUnbound
1dorB01Bound:FMNUnboundUnboundUnboundUnbound
1jqvA01Bound:FMNUnboundUnboundBound:OROUnbound
1jqvB01Bound:FMNUnboundUnboundBound:OROUnbound
1jqxA01Bound:FMNUnboundUnboundBound:OROUnbound
1jqxB01Bound:FMNUnboundUnboundBound:OROUnbound
1jrbA01Bound:FMNUnboundUnboundBound:OROUnbound
1jrbB01Bound:FMNUnboundUnboundBound:OROUnbound
1jrcA01Bound:FMNUnboundUnboundBound:OROUnbound
1jrcB01Bound:FMNUnboundUnboundBound:OROUnbound
1jubA01Bound:FMNUnboundUnboundUnboundUnbound
1jubB01Bound:FMNUnboundUnboundUnboundUnbound
1jueA01Bound:FMNUnboundUnboundUnboundUnbound
1jueB01Bound:FMNUnboundUnboundUnboundUnbound
1ovdA01Bound:FMNUnboundUnboundBound:OROUnbound
1ovdB01Bound:FMNUnboundUnboundBound:OROUnbound
2dorA01Bound:FMNUnboundUnboundBound:OROUnbound
2dorB01Bound:FMNUnboundUnboundBound:OROUnbound
1dorA02UnboundUnboundUnboundUnboundUnbound
1dorB02UnboundUnboundUnboundUnboundUnbound
1jqvA02UnboundUnboundUnboundUnboundUnbound
1jqvB02UnboundUnboundUnboundUnboundUnbound
1jqxA02UnboundUnboundUnboundUnboundUnbound
1jqxB02UnboundUnboundUnboundUnboundUnbound
1jrbA02UnboundUnboundUnboundUnboundUnbound
1jrbB02UnboundUnboundUnboundUnboundUnbound
1jrcA02UnboundUnboundUnboundUnboundUnbound
1jrcB02UnboundUnboundUnboundUnboundUnbound
1jubA02UnboundUnboundUnboundUnboundUnbound
1jubB02UnboundUnboundUnboundUnboundUnbound
1jueA02UnboundUnboundUnboundUnboundUnbound
1jueB02UnboundUnboundUnboundUnboundUnbound
1ovdA02UnboundUnboundUnboundUnboundUnbound
1ovdB02UnboundUnboundUnboundUnboundUnbound
2dorA02UnboundUnboundUnboundUnboundUnbound
2dorB02UnboundUnboundUnboundUnboundUnbound

Active-site residues
resource
literature [3], [5], [11]
pdbCatalytic residuescomment
1dorA01LYS 43;CYS 130

1dorB01LYS 43;CYS 130

1jqvA01LYS 43;CYS 130

1jqvB01LYS 43;CYS 130

1jqxA01LYS 43;CYS 130

1jqxB01LYS 43;CYS 130

1jrbA01LYS 43;CYS 130

1jrbB01LYS 43;CYS 130

1jrcA01LYS 43;CYS 130

1jrcB01LYS 43;CYS 130

1jubA01LYS 43;CYS 130
mutant K136E
1jubB01LYS 43;CYS 130
mutant K136E
1jueA01LYS 43;CYS 130

1jueB01LYS 43;CYS 130

1ovdA01LYS 43;CYS 130
mutant K136E
1ovdB01LYS 43;CYS 130
mutant K136E
2dorA01LYS 43;CYS 130

2dorB01LYS 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
ReferencesSectionsNo. 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]
PubMed ID1765126
JournalExperientia
Year1991
Volume47
Pages1139-1148
AuthorsSuckling CJ
TitleMolecular recognition in applied enzyme chemistry.
[2]
PubMed ID8732756
JournalProtein Sci
Year1996
Volume5
Pages852-6
AuthorsNielsen FS, Rowland P, Larsen S, Jensen KF
TitlePurification and characterization of dihydroorotate dehydrogenase A from Lactococcus lactis, crystallization and preliminary X-ray diffraction studies of the enzyme.
[3]
CommentsMUTAGENESIS OF LYS-43; CYS-130; ASN-132 AND LYS-164
Medline ID98070244
PubMed ID9405053
JournalBiochemistry
Year1997
Volume36
Pages16197-205
AuthorsBjornberg O, Rowland P, Larsen S, Jensen KF
TitleActive site of dihydroorotate dehydrogenase A from Lactococcus lactis investigated by chemical modification and mutagenesis.
Related Swiss-protP54321
[4]
CommentsX-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS)
Medline ID97184689
PubMed ID9032071
JournalStructure
Year1997
Volume5
Pages239-52
AuthorsRowland P, Nielsen FS, Jensen KF, Larsen S
TitleThe crystal structure of the flavin containing enzyme dihydroorotate dehydrogenase A from Lactococcus lactis.
Related PDB1dor
Related Swiss-protP54321
[5]
CommentsX-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS)
Medline ID98318035
PubMed ID9655329
JournalProtein Sci
Year1998
Volume7
Pages1269-79
AuthorsRowland P, Bjornberg O, Nielsen FS, Jensen KF, Larsen S
TitleThe crystal structure of Lactococcus lactis dihydroorotate dehydrogenase A complexed with the enzyme reaction product throws light on its enzymatic function.
Related PDB2dor
Related Swiss-protP54321
[6]
PubMed ID10545205
JournalArch Biochem Biophys
Year1999
Volume371
Pages191-201
AuthorsKahler AE, Nielsen FS, Switzer RL
TitleBiochemical characterization of the heteromeric Bacillus subtilis dihydroorotate dehydrogenase and its isolated subunits.
[7]
PubMed ID10074342
JournalBiochemistry
Year1999
Volume38
Pages2899-908
AuthorsBjornberg O, Gruner AC, Roepstorff P, Jensen KF
TitleThe activity of Escherichia coli dihydroorotate dehydrogenase is dependent on a conserved loop identified by sequence homology, mutagenesis, and limited proteolysis.
[8]
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.
[9]
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.
[10]
PubMed ID10694883
JournalTrends Biochem Sci
Year2000
Volume25
Pages126-32
AuthorsFraaije MW, Mattevi A
TitleFlavoenzymes: diverse catalysts with recurrent features.
[11]
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.
[12]
PubMed ID11284694
JournalBiochemistry
Year2001
Volume40
Pages4381-90
AuthorsPalfey BA, Bjornberg O, Jensen KF
TitleInsight into the chemistry of flavin reduction and oxidation in Escherichia coli dihydroorotate dehydrogenase obtained by rapid reaction studies.
[13]
PubMed ID12381841
JournalProtein Sci
Year2002
Volume11
Pages2575-83
AuthorsOttosen MB, Bjornberg O, Norager S, Larsen S, Palfey BA, Jensen KF
TitleThe dimeric dihydroorotate dehydrogenase A from Lactococcus lactis dissociates reversibly into inactive monomers.
[14]
CommentsX-ray crystallography
PubMed ID12732650
JournalJ Biol Chem
Year2003
Volume278
Pages28812-22
AuthorsNorager S, Arent S, Bjornberg O, Ottosen M, Lo Leggio L, Jensen KF, Larsen S
TitleLactococcus lactis dihydroorotate dehydrogenase A mutants reveal important facets of the enzymatic function.
Related PDB1jqv,1jqx,1jrb,1jrc,1jub,1jue,1ovd

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:

createdupdated
2004-10-252012-10-02
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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