Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Dihydroorotate dehydrogenase (quinone), mitochondrial

Gene

PFF0160c

Organism
Plasmodium falciparum (isolate 3D7)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Catalyzes the conversion of dihydroorotate to orotate with quinone as electron acceptor.

Catalytic activityi

(S)-dihydroorotate + a quinone = orotate + a quinol.

Cofactori

FMN3 PublicationsNote: Binds 1 FMN per subunit.3 Publications

Kineticsi

  1. KM=13.1 µM for 2,3-dimethoxy-5-methyl-6-(3-methyl-2-butenyl)-1,4-benzoquinone (CoQ1)1 Publication

    Pathwayi: UMP biosynthesis via de novo pathway

    This protein is involved in step 1 of the subpathway that synthesizes orotate from (S)-dihydroorotate (quinone route).
    Proteins known to be involved in this subpathway in this organism are:
    1. Dihydroorotate dehydrogenase (quinone), mitochondrial (PFF0160c)
    This subpathway is part of the pathway UMP biosynthesis via de novo pathway, which is itself part of Pyrimidine metabolism.
    View all proteins of this organism that are known to be involved in the subpathway that synthesizes orotate from (S)-dihydroorotate (quinone route), the pathway UMP biosynthesis via de novo pathway and in Pyrimidine metabolism.

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei229 – 2291Substrate
    Binding sitei249 – 2491FMN2 Publications
    Binding sitei342 – 3421FMN2 Publications
    Binding sitei342 – 3421Substrate
    Active sitei345 – 3451NucleophileBy similarity
    Binding sitei347 – 3471Substrate
    Binding sitei429 – 4291FMN2 Publications

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi225 – 2295FMN2 Publications
    Nucleotide bindingi477 – 4782FMN2 Publications
    Nucleotide bindingi505 – 5073FMN2 Publications
    Nucleotide bindingi528 – 5292FMN2 Publications

    GO - Molecular functioni

    • dihydroorotate dehydrogenase activity Source: GeneDB

    GO - Biological processi

    • 'de novo' pyrimidine nucleobase biosynthetic process Source: GeneDB
    • 'de novo' UMP biosynthetic process Source: UniProtKB-UniPathway
    • response to drug Source: GeneDB
    Complete GO annotation...

    Keywords - Molecular functioni

    Oxidoreductase

    Keywords - Biological processi

    Pyrimidine biosynthesis

    Keywords - Ligandi

    Flavoprotein, FMN

    Enzyme and pathway databases

    ReactomeiR-PFA-500753. Pyrimidine biosynthesis.
    UniPathwayiUPA00070; UER00946.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Dihydroorotate dehydrogenase (quinone), mitochondrial (EC:1.3.5.2)
    Short name:
    DHOdehase
    Alternative name(s):
    Dihydroorotate oxidase
    Gene namesi
    ORF Names:PFF0160c
    OrganismiPlasmodium falciparum (isolate 3D7)
    Taxonomic identifieri36329 [NCBI]
    Taxonomic lineageiEukaryotaAlveolataApicomplexaAconoidasidaHaemosporidaPlasmodiidaePlasmodiumPlasmodium (Laverania)
    Proteomesi
    • UP000001450 Componenti: Chromosome 6

    Organism-specific databases

    EuPathDBiPlasmoDB:PF3D7_0603300.

    Subcellular locationi

    Topology

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei143 – 16321HelicalSequence analysisAdd
    BLAST

    GO - Cellular componenti

    • integral component of membrane Source: UniProtKB-KW
    • mitochondrial inner membrane Source: GeneDB
    Complete GO annotation...

    Keywords - Cellular componenti

    Membrane, Mitochondrion, Mitochondrion inner membrane

    Pathology & Biotechi

    Chemistry

    DrugBankiDB01117. Atovaquone.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transit peptidei1 – 2323MitochondrionSequence analysisAdd
    BLAST
    Chaini24 – 569546Dihydroorotate dehydrogenase (quinone), mitochondrialPRO_0000029888Add
    BLAST

    Proteomic databases

    PRIDEiQ08210.

    Interactioni

    Subunit structurei

    Monomer.By similarity

    Chemistry

    BindingDBiQ08210.

    Structurei

    Secondary structure

    1
    569
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi166 – 17813Combined sources
    Helixi181 – 19313Combined sources
    Helixi206 – 2083Combined sources
    Beta strandi210 – 2123Combined sources
    Beta strandi215 – 2239Combined sources
    Turni225 – 2306Combined sources
    Beta strandi231 – 2333Combined sources
    Helixi234 – 2385Combined sources
    Turni239 – 2413Combined sources
    Beta strandi243 – 2508Combined sources
    Beta strandi263 – 2664Combined sources
    Turni267 – 2704Combined sources
    Beta strandi271 – 2744Combined sources
    Helixi283 – 29917Combined sources
    Helixi301 – 3033Combined sources
    Beta strandi307 – 3126Combined sources
    Helixi321 – 33212Combined sources
    Helixi333 – 3353Combined sources
    Beta strandi337 – 3426Combined sources
    Beta strandi346 – 3483Combined sources
    Helixi351 – 3555Combined sources
    Helixi357 – 37721Combined sources
    Helixi412 – 4154Combined sources
    Beta strandi418 – 4225Combined sources
    Beta strandi425 – 4306Combined sources
    Helixi436 – 44914Combined sources
    Beta strandi452 – 4565Combined sources
    Helixi467 – 4693Combined sources
    Beta strandi474 – 4785Combined sources
    Helixi479 – 4813Combined sources
    Helixi482 – 49514Combined sources
    Turni496 – 4983Combined sources
    Beta strandi502 – 5076Combined sources
    Helixi511 – 52010Combined sources
    Beta strandi522 – 5287Combined sources
    Helixi529 – 5346Combined sources
    Helixi535 – 5373Combined sources
    Helixi538 – 55215Combined sources
    Helixi558 – 5614Combined sources
    Helixi564 – 5663Combined sources

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1TV5X-ray2.40A158-569[»]
    3I65X-ray2.00A158-569[»]
    3I68X-ray2.40A158-569[»]
    3I6RX-ray2.50A158-569[»]
    3O8AX-ray2.30A158-569[»]
    3SFKX-ray2.95A158-569[»]
    4CQ8X-ray1.98A/B158-569[»]
    4CQ9X-ray2.72A/B158-569[»]
    4CQAX-ray2.82A/B158-569[»]
    4ORMX-ray2.07A158-569[»]
    4RX0X-ray2.25A158-569[»]
    5BOOX-ray2.80A/B158-569[»]
    5DELX-ray2.20A158-569[»]
    5FI8X-ray2.32A158-569[»]
    ProteinModelPortaliQ08210.
    SMRiQ08210. Positions 159-566.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ08210.

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni274 – 2785Substrate binding
    Regioni458 – 4592Substrate binding

    Sequence similaritiesi

    Keywords - Domaini

    Transit peptide, Transmembrane, Transmembrane helix

    Phylogenomic databases

    HOGENOMiHOG000225103.
    InParanoidiQ08210.
    KOiK00254.
    OMAiNIMNDES.
    PhylomeDBiQ08210.

    Family and domain databases

    Gene3Di3.20.20.70. 2 hits.
    InterProiIPR013785. Aldolase_TIM.
    IPR005720. Dihydroorotate_DH.
    IPR001295. Dihydroorotate_DH_CS.
    [Graphical view]
    PfamiPF01180. DHO_dh. 1 hit.
    [Graphical view]
    PROSITEiPS00911. DHODEHASE_1. 1 hit.
    PS00912. DHODEHASE_2. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    Q08210-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MISKLKPQFM FLPKKHILSY CRKDVLNLFE QKFYYTSKRK ESNNMKNESL
    60 70 80 90 100
    LRLINYNRYY NKIDSNNYYN GGKILSNDRQ YIYSPLCEYK KKINDISSYV
    110 120 130 140 150
    SVPFKINIRN LGTSNFVNNK KDVLDNDYIY ENIKKEKSKH KKIIFLLFVS
    160 170 180 190 200
    LFGLYGFFES YNPEFFLYDI FLKFCLKYID GEICHDLFLL LGKYNILPYD
    210 220 230 240 250
    TSNDSIYACT NIKHLDFINP FGVAAGFDKN GVCIDSILKL GFSFIEIGTI
    260 270 280 290 300
    TPRGQTGNAK PRIFRDVESR SIINSCGFNN MGCDKVTENL ILFRKRQEED
    310 320 330 340 350
    KLLSKHIVGV SIGKNKDTVN IVDDLKYCIN KIGRYADYIA INVSSPNTPG
    360 370 380 390 400
    LRDNQEAGKL KNIILSVKEE IDNLEKNNIM NDESTYNEDN KIVEKKNNFN
    410 420 430 440 450
    KNNSHMMKDA KDNFLWFNTT KKKPLVFVKL APDLNQEQKK EIADVLLETN
    460 470 480 490 500
    IDGMIISNTT TQINDIKSFE NKKGGVSGAK LKDISTKFIC EMYNYTNKQI
    510 520 530 540 550
    PIIASGGIFS GLDALEKIEA GASVCQLYSC LVFNGMKSAV QIKRELNHLL
    560
    YQRGYYNLKE AIGRKHSKS
    Length:569
    Mass (Da):65,558
    Last modified:February 1, 1995 - v1
    Checksum:i88880384EBD52FE3
    GO

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    L15446 Unassigned DNA. Translation: AAC37170.1.
    AL844505 Genomic DNA. Translation: CAG25203.1.
    RefSeqiXP_966023.1. XM_960930.1.

    Genome annotation databases

    EnsemblProtistsiPFF0160c:mRNA; PFF0160c:pep; PFF0160c.
    GeneDBiPF3D7_0603300.1:pep.
    GeneIDi3885966.
    KEGGipfa:PFF0160c.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    L15446 Unassigned DNA. Translation: AAC37170.1.
    AL844505 Genomic DNA. Translation: CAG25203.1.
    RefSeqiXP_966023.1. XM_960930.1.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1TV5X-ray2.40A158-569[»]
    3I65X-ray2.00A158-569[»]
    3I68X-ray2.40A158-569[»]
    3I6RX-ray2.50A158-569[»]
    3O8AX-ray2.30A158-569[»]
    3SFKX-ray2.95A158-569[»]
    4CQ8X-ray1.98A/B158-569[»]
    4CQ9X-ray2.72A/B158-569[»]
    4CQAX-ray2.82A/B158-569[»]
    4ORMX-ray2.07A158-569[»]
    4RX0X-ray2.25A158-569[»]
    5BOOX-ray2.80A/B158-569[»]
    5DELX-ray2.20A158-569[»]
    5FI8X-ray2.32A158-569[»]
    ProteinModelPortaliQ08210.
    SMRiQ08210. Positions 159-566.
    ModBaseiSearch...
    MobiDBiSearch...

    Chemistry

    BindingDBiQ08210.
    DrugBankiDB01117. Atovaquone.

    Proteomic databases

    PRIDEiQ08210.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsemblProtistsiPFF0160c:mRNA; PFF0160c:pep; PFF0160c.
    GeneDBiPF3D7_0603300.1:pep.
    GeneIDi3885966.
    KEGGipfa:PFF0160c.

    Organism-specific databases

    EuPathDBiPlasmoDB:PF3D7_0603300.

    Phylogenomic databases

    HOGENOMiHOG000225103.
    InParanoidiQ08210.
    KOiK00254.
    OMAiNIMNDES.
    PhylomeDBiQ08210.

    Enzyme and pathway databases

    UniPathwayiUPA00070; UER00946.
    ReactomeiR-PFA-500753. Pyrimidine biosynthesis.

    Miscellaneous databases

    EvolutionaryTraceiQ08210.

    Family and domain databases

    Gene3Di3.20.20.70. 2 hits.
    InterProiIPR013785. Aldolase_TIM.
    IPR005720. Dihydroorotate_DH.
    IPR001295. Dihydroorotate_DH_CS.
    [Graphical view]
    PfamiPF01180. DHO_dh. 1 hit.
    [Graphical view]
    PROSITEiPS00911. DHODEHASE_1. 1 hit.
    PS00912. DHODEHASE_2. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Publicationsi

    « Hide 'large scale' publications
    1. "The dihydroorotate dehydrogenase gene homologue of Plasmodium falciparum."
      Leblanc S.B., Wilson C.M.
      Mol. Biochem. Parasitol. 60:349-352(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: Isolate 3D7.
    3. "Sequence of Plasmodium falciparum chromosomes 1, 3-9 and 13."
      Hall N., Pain A., Berriman M., Churcher C.M., Harris B., Harris D., Mungall K.L., Bowman S., Atkin R., Baker S., Barron A., Brooks K., Buckee C.O., Burrows C., Cherevach I., Chillingworth C., Chillingworth T., Christodoulou Z.
      , Clark L., Clark R., Corton C., Cronin A., Davies R.M., Davis P., Dear P., Dearden F., Doggett J., Feltwell T., Goble A., Goodhead I., Gwilliam R., Hamlin N., Hance Z., Harper D., Hauser H., Hornsby T., Holroyd S., Horrocks P., Humphray S., Jagels K., James K.D., Johnson D., Kerhornou A., Knights A., Konfortov B., Kyes S., Larke N., Lawson D., Lennard N., Line A., Maddison M., Mclean J., Mooney P., Moule S., Murphy L., Oliver K., Ormond D., Price C., Quail M.A., Rabbinowitsch E., Rajandream M.A., Rutter S., Rutherford K.M., Sanders M., Simmonds M., Seeger K., Sharp S., Smith R., Squares R., Squares S., Stevens K., Taylor K., Tivey A., Unwin L., Whitehead S., Woodward J.R., Sulston J.E., Craig A., Newbold C., Barrell B.G.
      Nature 419:527-531(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: Isolate 3D7.
    4. "Structure of Plasmodium falciparum dihydroorotate dehydrogenase with a bound inhibitor."
      Hurt D.E., Widom J., Clardy J.
      Acta Crystallogr. D 62:312-323(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 158-569 IN COMPLEX WITH FMN; OROTATE AND INHIBITOR, COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES.
    5. "Structural plasticity of malaria dihydroorotate dehydrogenase allows selective binding of diverse chemical scaffolds."
      Deng X., Gujjar R., El Mazouni F., Kaminsky W., Malmquist N.A., Goldsmith E.J., Rathod P.K., Phillips M.A.
      J. Biol. Chem. 284:26999-27009(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 158-569 IN COMPLEXES WITH FMN; OROTATE AND INHIBITORS, COFACTOR.
    6. Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 158-569 IN COMPLEX WITH FMN; OROTATE AND INHIBITOR, COFACTOR.

    Entry informationi

    Entry nameiPYRD_PLAF7
    AccessioniPrimary (citable) accession number: Q08210
    Secondary accession number(s): Q6LFN3
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: February 1, 1995
    Last sequence update: February 1, 1995
    Last modified: July 6, 2016
    This is version 120 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference 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.