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Protein

Dihydroorotate dehydrogenase A (fumarate)

Gene

pyrDA

Organism
Lactococcus lactis subsp. cremoris (strain MG1363)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Catalyzes the conversion of dihydroorotate to orotate with fumarate as the electron acceptor. Molecular oxygen can replace fumarate in vitro, but cannot use NAD+ as an electron acceptor.1 Publication

Catalytic activityi

(S)-dihydroorotate + fumarate = orotate + succinate.1 Publication

Cofactori

FMN2 PublicationsNote: Binds 1 FMN per subunit.2 Publications

Kineticsi

  1. KM=18 µM for dihydroorotate1 Publication
  2. KM=250 µM for fumarate1 Publication
  1. Vmax=18.6 µmol/min/mg enzyme1 Publication

Pathwayi: UMP biosynthesis via de novo pathway

This protein is involved in the pathway UMP biosynthesis via de novo pathway, which is part of Pyrimidine metabolism.
View all proteins of this organism that are known to be involved in the pathway UMP biosynthesis via de novo pathway and in Pyrimidine metabolism.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei19 – 191FMN2 Publications
Binding sitei43 – 431Substrate
Binding sitei127 – 1271FMN2 Publications
Binding sitei127 – 1271Substrate
Active sitei130 – 1301Nucleophile
Binding sitei164 – 1641FMN2 Publications
Binding sitei192 – 1921FMN; via carbonyl oxygen2 Publications
Binding sitei221 – 2211FMN; via amide nitrogen2 Publications

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi43 – 442FMN2 Publications
Nucleotide bindingi249 – 2502FMN2 Publications
Nucleotide bindingi271 – 2722FMN2 Publications

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Oxidoreductase

Keywords - Biological processi

Pyrimidine biosynthesis

Keywords - Ligandi

Flavoprotein, FMN

Enzyme and pathway databases

BioCyciLLAC416870:GCDT-976-MONOMER.
BRENDAi1.3.1.14. 2903.
UniPathwayiUPA00070.

Names & Taxonomyi

Protein namesi
Recommended name:
Dihydroorotate dehydrogenase A (fumarate) (EC:1.3.98.1)
Short name:
DHOD A
Short name:
DHODase A
Short name:
DHOdehase A
Gene namesi
Name:pyrDA
Ordered Locus Names:llmg_0952
OrganismiLactococcus lactis subsp. cremoris (strain MG1363)
Taxonomic identifieri416870 [NCBI]
Taxonomic lineageiBacteriaFirmicutesBacilliLactobacillalesStreptococcaceaeLactococcus
Proteomesi
  • UP000000364 Componenti: Chromosome

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi43 – 431K → A: More than 500-fold reduction of enzymatic activity with oxygen or DCIP as electron acceptor. 1 Publication
Mutagenesisi43 – 431K → E: 40-fold reduction of enzymatic activity with oxygen as electron acceptor; more than 120-fold reduction with DCIP as electron acceptor. 1 Publication
Mutagenesisi50 – 501R → E: Steady state kinetics comparable to wild-type; 3-fold decrease in flavin bleaching rate. 1 Publication
Mutagenesisi56 – 561P → A: More than 500-fold reduction of enzymatic activity. 1 Publication
Mutagenesisi57 – 571R → A: More active than wild-type, especially with 2,6-dichloroindophenol as electron acceptor. 1 Publication
Mutagenesisi67 – 671N → A: 100-fold lower affinity for dihydroorotate. 1 Publication
Mutagenesisi127 – 1271N → A: 70-fold lower affinity for dihydroorotate; inhibited by milimolar concentrations of fumarate. 1 Publication
Mutagenesisi129 – 1291S → A: 6-fold lower enzymatic activity with fumarate as electron acceptor. 1 Publication
Mutagenesisi130 – 1301C → A or S: Almost total loss of activity with oxygen or 2,6-dichloroindophenol as electron acceptor. 1 Publication
Mutagenesisi131 – 1311P → A: 4.5-fold lower enzymatic activity with fumarate and 2,6-dichloroindophenol as electron acceptor. 1 Publication
Mutagenesisi132 – 1321N → A: 54-fold reduction of enzymatic activity with oxygen as electron acceptor; more than 250-fold reduction with 2,6-dichloroindophenol as electron acceptor. 2 Publications
Mutagenesisi136 – 1361K → A: Slightly higher affinity to dihydroorotate; 2-fold decrease in flavin bleaching rate. 1 Publication
Mutagenesisi164 – 1641K → A: Almost total loss of activity with oxygen or 2,6-dichloroindophenol as electron acceptor. 1 Publication
Mutagenesisi193 – 1931N → A: 500-fold lower affinity for dihydroorotate; inhibited by milimolar concentrations of fumarate. 1 Publication
Mutagenesisi213 – 2131K → A: 7-fold decrease in enzymatic activity; 50-fold decrease in flavin bleaching rate. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 311311Dihydroorotate dehydrogenase A (fumarate)PRO_0000285239Add
BLAST

Interactioni

Subunit structurei

Homodimer.2 Publications

Protein-protein interaction databases

STRINGi416870.llmg_0952.

Structurei

Secondary structure

1
311
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi4 – 63Combined sources
Beta strandi9 – 179Combined sources
Helixi26 – 349Combined sources
Beta strandi58 – 614Combined sources
Beta strandi64 – 674Combined sources
Helixi76 – 8914Combined sources
Beta strandi92 – 943Combined sources
Beta strandi97 – 1004Combined sources
Helixi105 – 11713Combined sources
Beta strandi122 – 1287Combined sources
Beta strandi133 – 1353Combined sources
Helixi139 – 1413Combined sources
Helixi143 – 15311Combined sources
Turni154 – 1563Combined sources
Beta strandi161 – 1655Combined sources
Helixi171 – 18111Combined sources
Beta strandi188 – 1914Combined sources
Beta strandi195 – 1995Combined sources
Turni203 – 2064Combined sources
Beta strandi207 – 2093Combined sources
Helixi212 – 2154Combined sources
Beta strandi216 – 2216Combined sources
Helixi222 – 2243Combined sources
Helixi225 – 23612Combined sources
Beta strandi243 – 2508Combined sources
Helixi254 – 26310Combined sources
Beta strandi266 – 2705Combined sources
Helixi272 – 2776Combined sources
Helixi281 – 29616Combined sources
Helixi301 – 3033Combined sources
Turni304 – 3063Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1DORX-ray2.00A/B1-311[»]
1JQVX-ray2.10A/B1-311[»]
1JQXX-ray1.70A/B1-311[»]
1JRBX-ray1.90A/B1-311[»]
1JRCX-ray1.80A/B1-311[»]
1JUBX-ray1.40A/B1-311[»]
1JUEX-ray1.80A/B1-311[»]
1NFCmodel-A1-311[»]
1OVDX-ray2.25A/B1-311[»]
2BSLX-ray2.30A/B1-311[»]
2BX7X-ray2.04A/B1-311[»]
2DORX-ray2.00A/B1-311[»]
ProteinModelPortaliA2RJT9.
SMRiA2RJT9. Positions 1-311.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiA2RJT9.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni67 – 715Substrate binding
Regioni193 – 1942Substrate binding

Sequence similaritiesi

Phylogenomic databases

eggNOGiENOG4107RY0. Bacteria.
COG0167. LUCA.
HOGENOMiHOG000225104.
KOiK00226.
OMAiMAKKGYE.
OrthoDBiEOG6NPM9S.

Family and domain databases

Gene3Di3.20.20.70. 1 hit.
HAMAPiMF_00224. DHO_dh_type1.
InterProiIPR013785. Aldolase_TIM.
IPR005720. Dihydroorotate_DH.
IPR024920. Dihydroorotate_DH_1.
IPR012135. Dihydroorotate_DH_1_2.
IPR001295. Dihydroorotate_DH_CS.
[Graphical view]
PfamiPF01180. DHO_dh. 1 hit.
[Graphical view]
PIRSFiPIRSF000164. DHO_oxidase. 1 hit.
TIGRFAMsiTIGR01037. pyrD_sub1_fam. 1 hit.
PROSITEiPS00911. DHODEHASE_1. 1 hit.
PS00912. DHODEHASE_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

A2RJT9-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MLNTTFANAK FANPFMNASG VHCMTIEDLE ELKASQAGAY ITKSSTLEKR
60 70 80 90 100
EGNPLPRYVD LELGSINSMG LPNLGFDYYL DYVLKNQKEN AQEGPIFFSI
110 120 130 140 150
AGMSAAENIA MLKKIQESDF SGITELNLSC PNVPGKPQLA YDFEATEKLL
160 170 180 190 200
KEVFTFFTKP LGVKLPPYFD LVHFDIMAEI LNQFPLTYVN SVNSIGNGLF
210 220 230 240 250
IDPEAESVVI KPKDGFGGIG GAYIKPTALA NVRAFYTRLK PEIQIIGTGG
260 270 280 290 300
IETGQDAFEH LLCGATMLQI GTALHKEGPA IFDRIIKELE EIMNQKGYQS
310
IADFHGKLKS L
Length:311
Mass (Da):34,210
Last modified:March 6, 2007 - v1
Checksum:i30157E3C2791CDD7
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X74206 Genomic DNA. Translation: CAA52279.1.
AM406671 Genomic DNA. Translation: CAL97544.1.
RefSeqiWP_011834894.1. NC_009004.1.

Genome annotation databases

EnsemblBacteriaiCAL97544; CAL97544; llmg_0952.
KEGGillm:llmg_0952.
PATRICi22283022. VBILacLac4574_0970.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X74206 Genomic DNA. Translation: CAA52279.1.
AM406671 Genomic DNA. Translation: CAL97544.1.
RefSeqiWP_011834894.1. NC_009004.1.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1DORX-ray2.00A/B1-311[»]
1JQVX-ray2.10A/B1-311[»]
1JQXX-ray1.70A/B1-311[»]
1JRBX-ray1.90A/B1-311[»]
1JRCX-ray1.80A/B1-311[»]
1JUBX-ray1.40A/B1-311[»]
1JUEX-ray1.80A/B1-311[»]
1NFCmodel-A1-311[»]
1OVDX-ray2.25A/B1-311[»]
2BSLX-ray2.30A/B1-311[»]
2BX7X-ray2.04A/B1-311[»]
2DORX-ray2.00A/B1-311[»]
ProteinModelPortaliA2RJT9.
SMRiA2RJT9. Positions 1-311.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi416870.llmg_0952.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsemblBacteriaiCAL97544; CAL97544; llmg_0952.
KEGGillm:llmg_0952.
PATRICi22283022. VBILacLac4574_0970.

Phylogenomic databases

eggNOGiENOG4107RY0. Bacteria.
COG0167. LUCA.
HOGENOMiHOG000225104.
KOiK00226.
OMAiMAKKGYE.
OrthoDBiEOG6NPM9S.

Enzyme and pathway databases

UniPathwayiUPA00070.
BioCyciLLAC416870:GCDT-976-MONOMER.
BRENDAi1.3.1.14. 2903.

Miscellaneous databases

EvolutionaryTraceiA2RJT9.

Family and domain databases

Gene3Di3.20.20.70. 1 hit.
HAMAPiMF_00224. DHO_dh_type1.
InterProiIPR013785. Aldolase_TIM.
IPR005720. Dihydroorotate_DH.
IPR024920. Dihydroorotate_DH_1.
IPR012135. Dihydroorotate_DH_1_2.
IPR001295. Dihydroorotate_DH_CS.
[Graphical view]
PfamiPF01180. DHO_dh. 1 hit.
[Graphical view]
PIRSFiPIRSF000164. DHO_oxidase. 1 hit.
TIGRFAMsiTIGR01037. pyrD_sub1_fam. 1 hit.
PROSITEiPS00911. DHODEHASE_1. 1 hit.
PS00912. DHODEHASE_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Two different dihydroorotate dehydrogenases in Lactococcus lactis."
    Andersen P.S., Jansen P.J.G., Hammer K.
    J. Bacteriol. 176:3975-3982(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, CATALYTIC ACTIVITY, SUBSTRATE SPECIFICITY.
    Strain: MG1363.
  2. "The complete genome sequence of the lactic acid bacterial paradigm Lactococcus lactis subsp. cremoris MG1363."
    Wegmann U., O'Connell-Motherway M., Zomer A., Buist G., Shearman C., Canchaya C., Ventura M., Goesmann A., Gasson M.J., Kuipers O.P., van Sinderen D., Kok J.
    J. Bacteriol. 189:3256-3270(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: MG1363.
  3. "Active site of dihydroorotate dehydrogenase A from Lactococcus lactis investigated by chemical modification and mutagenesis."
    Bjoernberg O., Rowland P., Larsen S., Jensen K.F.
    Biochemistry 36:16197-16205(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: MUTAGENESIS OF LYS-43; CYS-130; ASN-132 AND LYS-164.
    Strain: MG1363.
  4. "The crystal structure of the flavin containing enzyme dihydroorotate dehydrogenase A from Lactococcus lactis."
    Rowland P., Nielsen F.S., Jensen K.F., Larsen S.
    Structure 5:239-252(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) IN COMPLEX WITH FMN, COFACTOR, SUBUNIT.
    Strain: MG1363.
  5. "The crystal structure of Lactococcus lactis dihydroorotate dehydrogenase A complexed with the enzyme reaction product throws light on its enzymatic function."
    Rowland P., Bjoernberg O., Nielsen F.S., Jensen K.F., Larsen S.
    Protein Sci. 7:1269-1279(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) IN COMPLEX WITH FMN AND OROTATE, COFACTOR, REACTION MECHANISM.
    Strain: MG1363.
  6. "Lactococcus lactis dihydroorotate dehydrogenase A mutants reveal important facets of the enzymatic function."
    Noerager S., Arent S., Bjoernberg O., Ottosen M., Lo Leggio L., Jensen K.F., Larsen S.
    J. Biol. Chem. 278:28812-28822(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF WILD-TYPE AND MUTANTS ALA-56; ARG-56; ALA-67; LYS-136 AND GLU-213 IN COMPLEXES WITH FMN AND SUBSTRATE, MUTAGENESIS OF ARG-50; PRO-56; ARG-57; ASN-67; ASN-127; SER-129; PRO-131; ASN-132; LYS-136; ASN-193 AND LYS-213, BIOPHYSICOCHEMICAL PROPERTIES.
    Strain: MG1363.

Entry informationi

Entry nameiPYRDA_LACLM
AccessioniPrimary (citable) accession number: A2RJT9
Secondary accession number(s): P54321
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 1, 2007
Last sequence update: March 6, 2007
Last modified: June 8, 2016
This is version 65 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programProkaryotic Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome

Documents

  1. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.