PYRD_CANAL
ID PYRD_CANAL Reviewed; 444 AA.
AC Q874I4; A0A1D8PEM9; Q5APC9;
DT 31-AUG-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 1.
DT 03-AUG-2022, entry version 123.
DE RecName: Full=Dihydroorotate dehydrogenase (quinone), mitochondrial;
DE Short=DHOD;
DE Short=DHODase;
DE Short=DHOdehase;
DE EC=1.3.5.2;
DE AltName: Full=Dihydroorotate oxidase;
DE Flags: Precursor;
GN Name=URA9; Synonyms=URA1; OrderedLocusNames=CAALFM_C109720WA;
GN ORFNames=CaO19.12299, CaO19.4836;
OS Candida albicans (strain SC5314 / ATCC MYA-2876) (Yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Debaryomycetaceae; Candida/Lodderomyces clade; Candida.
OX NCBI_TaxID=237561;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=15014982; DOI=10.1007/s00438-004-0995-7;
RA Gojkovic Z., Knecht W., Zameitat E., Warneboldt J., Coutelis J.-B.,
RA Pynyaha Y., Neuveglise C., Moeller K., Loeffler M., Piskur J.;
RT "Horizontal gene transfer promoted evolution of the ability to propagate
RT under anaerobic conditions in yeasts.";
RL Mol. Genet. Genomics 271:387-393(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=MMRL 2010;
RX PubMed=15947202; DOI=10.1128/ec.4.6.1102-1115.2005;
RA Hall C.R., Brachat S., Dietrich F.S.;
RT "Contribution of horizontal gene transfer to the evolution of Saccharomyces
RT cerevisiae.";
RL Eukaryot. Cell 4:1102-1115(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=SC5314 / ATCC MYA-2876;
RX PubMed=15123810; DOI=10.1073/pnas.0401648101;
RA Jones T., Federspiel N.A., Chibana H., Dungan J., Kalman S., Magee B.B.,
RA Newport G., Thorstenson Y.R., Agabian N., Magee P.T., Davis R.W.,
RA Scherer S.;
RT "The diploid genome sequence of Candida albicans.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:7329-7334(2004).
RN [4]
RP GENOME REANNOTATION.
RC STRAIN=SC5314 / ATCC MYA-2876;
RX PubMed=17419877; DOI=10.1186/gb-2007-8-4-r52;
RA van het Hoog M., Rast T.J., Martchenko M., Grindle S., Dignard D.,
RA Hogues H., Cuomo C., Berriman M., Scherer S., Magee B.B., Whiteway M.,
RA Chibana H., Nantel A., Magee P.T.;
RT "Assembly of the Candida albicans genome into sixteen supercontigs aligned
RT on the eight chromosomes.";
RL Genome Biol. 8:RESEARCH52.1-RESEARCH52.12(2007).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND GENOME REANNOTATION.
RC STRAIN=SC5314 / ATCC MYA-2876;
RX PubMed=24025428; DOI=10.1186/gb-2013-14-9-r97;
RA Muzzey D., Schwartz K., Weissman J.S., Sherlock G.;
RT "Assembly of a phased diploid Candida albicans genome facilitates allele-
RT specific measurements and provides a simple model for repeat and indel
RT structure.";
RL Genome Biol. 14:RESEARCH97.1-RESEARCH97.14(2013).
RN [6]
RP FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, AND COFACTOR.
RX PubMed=16774642; DOI=10.1111/j.1742-4658.2006.05327.x;
RA Zameitat E., Gojkovic Z., Knecht W., Piskur J., Loeffler M.;
RT "Biochemical characterization of recombinant dihydroorotate dehydrogenase
RT from the opportunistic pathogenic yeast Candida albicans.";
RL FEBS J. 273:3183-3191(2006).
CC -!- FUNCTION: In the de novo pyrimidine biosynthesis pathway, catalyzes the
CC stereospecific oxidation of (S)-dihydroorotate to orotate with
CC reduction of flavin and the transfer of electrons to ubiquinone, which
CC is part of the repiratory chain. Does not use fumarate and NAD as
CC electron acceptors. {ECO:0000269|PubMed:16774642}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(S)-dihydroorotate + a quinone = a quinol + orotate;
CC Xref=Rhea:RHEA:30187, ChEBI:CHEBI:24646, ChEBI:CHEBI:30839,
CC ChEBI:CHEBI:30864, ChEBI:CHEBI:132124; EC=1.3.5.2;
CC -!- COFACTOR:
CC Name=FMN; Xref=ChEBI:CHEBI:58210; Evidence={ECO:0000250};
CC Note=Binds 1 FMN per subunit. {ECO:0000250};
CC -!- ACTIVITY REGULATION: Inhibited by the dianisidine derivative redoxal
CC and by brequinar.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=108 uM for (S)-dihydroorotate {ECO:0000269|PubMed:16774642};
CC KM=42 uM for decylubiquinone {ECO:0000269|PubMed:16774642};
CC KM=122 uM for 2,6-dichloroindophenol {ECO:0000269|PubMed:16774642};
CC Vmax=6 umol/min/mg enzyme {ECO:0000269|PubMed:16774642};
CC pH dependence:
CC Optimum pH is 8.0-8.5. {ECO:0000269|PubMed:16774642};
CC -!- PATHWAY: Pyrimidine metabolism; UMP biosynthesis via de novo pathway;
CC orotate from (S)-dihydroorotate (quinone route): step 1/1.
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane {ECO:0000250};
CC Single-pass membrane protein {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the dihydroorotate dehydrogenase family. Type 2
CC subfamily. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AY230865; AAO74621.1; -; Genomic_DNA.
DR EMBL; AY240959; AAP39962.1; -; Genomic_DNA.
DR EMBL; CP017623; AOW26604.1; -; Genomic_DNA.
DR RefSeq; XP_723522.1; XM_718429.1.
DR AlphaFoldDB; Q874I4; -.
DR SMR; Q874I4; -.
DR STRING; 237561.Q874I4; -.
DR PRIDE; Q874I4; -.
DR GeneID; 3634819; -.
DR KEGG; cal:CAALFM_C109720WA; -.
DR CGD; CAL0000178448; URA1.
DR VEuPathDB; FungiDB:C1_09720W_A; -.
DR eggNOG; KOG1436; Eukaryota.
DR HOGENOM; CLU_013640_4_0_1; -.
DR InParanoid; Q874I4; -.
DR OMA; ERIKMGA; -.
DR OrthoDB; 1194348at2759; -.
DR BRENDA; 1.3.5.2; 1096.
DR SABIO-RK; Q874I4; -.
DR UniPathway; UPA00070; UER00946.
DR PRO; PR:Q874I4; -.
DR Proteomes; UP000000559; Chromosome 1.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0031304; C:intrinsic component of mitochondrial inner membrane; NAS:CGD.
DR GO; GO:0005743; C:mitochondrial inner membrane; IBA:GO_Central.
DR GO; GO:0004152; F:dihydroorotate dehydrogenase activity; IDA:CGD.
DR GO; GO:0006207; P:'de novo' pyrimidine nucleobase biosynthetic process; IBA:GO_Central.
DR GO; GO:0044205; P:'de novo' UMP biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0009220; P:pyrimidine ribonucleotide biosynthetic process; IBA:GO_Central.
DR CDD; cd04738; DHOD_2_like; 1.
DR Gene3D; 3.20.20.70; -; 1.
DR InterPro; IPR013785; Aldolase_TIM.
DR InterPro; IPR005720; Dihydroorotate_DH.
DR InterPro; IPR005719; Dihydroorotate_DH_2.
DR InterPro; IPR001295; Dihydroorotate_DH_CS.
DR Pfam; PF01180; DHO_dh; 1.
DR TIGRFAMs; TIGR01036; pyrD_sub2; 1.
DR PROSITE; PS00911; DHODEHASE_1; 1.
DR PROSITE; PS00912; DHODEHASE_2; 1.
PE 1: Evidence at protein level;
KW Flavoprotein; FMN; Membrane; Mitochondrion; Mitochondrion inner membrane;
KW Oxidoreductase; Pyrimidine biosynthesis; Reference proteome;
KW Transit peptide; Transmembrane; Transmembrane helix.
FT TRANSIT 1..27
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 28..444
FT /note="Dihydroorotate dehydrogenase (quinone),
FT mitochondrial"
FT /id="PRO_0000029891"
FT TRANSMEM 33..53
FT /note="Helical"
FT /evidence="ECO:0000255"
FT ACT_SITE 257
FT /note="Nucleophile"
FT /evidence="ECO:0000250"
FT BINDING 124..128
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250"
FT BINDING 128
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 148
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250"
FT BINDING 173..177
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 224
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250"
FT BINDING 254..259
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 254
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250"
FT BINDING 300
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250"
FT BINDING 328
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250"
FT BINDING 329..330
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 355
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250"
FT BINDING 385
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250"
FT BINDING 406..407
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250"
SQ SEQUENCE 444 AA; 48426 MW; CD37C62FFA2E6902 CRC64;
MFRPSIKFKQ STLSIIARRL KSSAQHQPLR SSFVPSPIVF VAGLAVAAVG GYYCLDSRSA
IHEYVLCPLI RTFTDAESGH KLGIFFMKYG LSPRLLDDGK NDQSDVLGVQ VFGHKLKNPI
GLAAGLDKDG EAIESLFNCG FSYVEIGSIT PEPQPGNPQP RFFRLPKDDA VINRYGFNSS
GHFNVLATLK LRFNKLLNKF GTSHSSEQHP FSNAFQQGKL LGINLGKNKF GDEVNDYVKG
VERLGPYADV LVINVSSPNT PGLRDLQSEA KLTNLLTTVV KERNVLGKNL LGNKPPVLVK
VAPDLTEPEI ESIANSAKEA KVDGIIISNT TIQRPVDRLL TTDKQLINQA GGLSGKPLKP
LSLKALRTLR KYTKDSDLVL IGCGGISNGK DALEFGKAGA TFIELYTAFA YKGPGLVGKI
RDELAEELRK EGKTWEQIIG SDDK
