PYRD_TRYB2
ID PYRD_TRYB2 Reviewed; 313 AA.
AC Q57U83;
DT 31-MAY-2011, integrated into UniProtKB/Swiss-Prot.
DT 10-MAY-2005, sequence version 1.
DT 03-AUG-2022, entry version 99.
DE RecName: Full=Dihydroorotate dehydrogenase (fumarate);
DE Short=DHOD;
DE Short=DHODase;
DE Short=DHOdehase;
DE EC=1.3.98.1;
DE AltName: Full=Dihydroorotate oxidase;
GN ORFNames=Tb927.5.3830;
OS Trypanosoma brucei brucei (strain 927/4 GUTat10.1).
OC Eukaryota; Discoba; Euglenozoa; Kinetoplastea; Metakinetoplastina;
OC Trypanosomatida; Trypanosomatidae; Trypanosoma.
OX NCBI_TaxID=185431;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=927/4 GUTat10.1 {ECO:0000312|Proteomes:UP000008524};
RX PubMed=16020726; DOI=10.1126/science.1112642;
RA Berriman M., Ghedin E., Hertz-Fowler C., Blandin G., Renauld H.,
RA Bartholomeu D.C., Lennard N.J., Caler E., Hamlin N.E., Haas B., Bohme U.,
RA Hannick L., Aslett M.A., Shallom J., Marcello L., Hou L., Wickstead B.,
RA Alsmark U.C.M., Arrowsmith C., Atkin R.J., Barron A.J., Bringaud F.,
RA Brooks K., Carrington M., Cherevach I., Chillingworth T.J., Churcher C.,
RA Clark L.N., Corton C.H., Cronin A., Davies R.M., Doggett J., Djikeng A.,
RA Feldblyum T., Field M.C., Fraser A., Goodhead I., Hance Z., Harper D.,
RA Harris B.R., Hauser H., Hostetler J., Ivens A., Jagels K., Johnson D.,
RA Johnson J., Jones K., Kerhornou A.X., Koo H., Larke N., Landfear S.,
RA Larkin C., Leech V., Line A., Lord A., Macleod A., Mooney P.J., Moule S.,
RA Martin D.M., Morgan G.W., Mungall K., Norbertczak H., Ormond D., Pai G.,
RA Peacock C.S., Peterson J., Quail M.A., Rabbinowitsch E., Rajandream M.A.,
RA Reitter C., Salzberg S.L., Sanders M., Schobel S., Sharp S., Simmonds M.,
RA Simpson A.J., Tallon L., Turner C.M., Tait A., Tivey A.R., Van Aken S.,
RA Walker D., Wanless D., Wang S., White B., White O., Whitehead S.,
RA Woodward J., Wortman J., Adams M.D., Embley T.M., Gull K., Ullu E.,
RA Barry J.D., Fairlamb A.H., Opperdoes F., Barrell B.G., Donelson J.E.,
RA Hall N., Fraser C.M., Melville S.E., El-Sayed N.M.A.;
RT "The genome of the African trypanosome Trypanosoma brucei.";
RL Science 309:416-422(2005).
RN [2]
RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) IN COMPLEX WITH FMN AND OROTATE,
RP COFACTOR, SUBUNIT, BIOPHYSICOCHEMICAL PROPERTIES, AND ENZYME KINETICS.
RC STRAIN=927/4 GUTat10.1;
RX PubMed=18312275; DOI=10.1111/j.1365-2958.2008.06131.x;
RA Arakaki T.L., Buckner F.S., Gillespie J.R., Malmquist N.A., Phillips M.A.,
RA Kalyuzhniy O., Luft J.R., DeTitta G.T., Verlinde C.L.M.J.,
RA Van Voorhis W.C., Hol W.G., Merritt E.A.;
RT "Characterization of Trypanosoma brucei dihydroorotate dehydrogenase as a
RT possible drug target; structural, kinetic and RNAi studies.";
RL Mol. Microbiol. 68:37-50(2008).
CC -!- FUNCTION: Catalyzes the conversion of dihydroorotate to orotate with
CC fumarate as the electron acceptor. Molecular oxygen can replace
CC fumarate in vitro.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(S)-dihydroorotate + fumarate = orotate + succinate;
CC Xref=Rhea:RHEA:30059, ChEBI:CHEBI:29806, ChEBI:CHEBI:30031,
CC ChEBI:CHEBI:30839, ChEBI:CHEBI:30864; EC=1.3.98.1;
CC -!- COFACTOR:
CC Name=FMN; Xref=ChEBI:CHEBI:58210;
CC Evidence={ECO:0000269|PubMed:18312275};
CC Note=Binds 1 FMN per subunit. {ECO:0000269|PubMed:18312275};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=14 uM for dihydroorotate {ECO:0000269|PubMed:18312275};
CC KM=80 uM for fumarate {ECO:0000269|PubMed:18312275};
CC pH dependence:
CC Optimum pH is 7.8. {ECO:0000269|PubMed:18312275};
CC -!- PATHWAY: Pyrimidine metabolism; UMP biosynthesis via de novo pathway.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:18312275}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the dihydroorotate dehydrogenase family. Type 1
CC subfamily. {ECO:0000305}.
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DR EMBL; AC159455; AAX70836.1; -; Genomic_DNA.
DR EMBL; CP000068; AAZ11494.1; -; Genomic_DNA.
DR RefSeq; XP_845053.1; XM_839960.1.
DR PDB; 2B4G; X-ray; 1.95 A; A/B/C/D=1-313.
DR PDB; 5XFV; X-ray; 1.79 A; A/B/C/D=1-313.
DR PDB; 5XFW; X-ray; 1.60 A; A/B/C/D=1-313.
DR PDBsum; 2B4G; -.
DR PDBsum; 5XFV; -.
DR PDBsum; 5XFW; -.
DR AlphaFoldDB; Q57U83; -.
DR SMR; Q57U83; -.
DR STRING; 5691.AAZ11494; -.
DR PaxDb; Q57U83; -.
DR GeneID; 3657493; -.
DR KEGG; tbr:Tb927.5.3830; -.
DR VEuPathDB; TriTrypDB:Tb927.5.3830; -.
DR eggNOG; KOG1436; Eukaryota.
DR InParanoid; Q57U83; -.
DR OMA; SCPHAKG; -.
DR UniPathway; UPA00070; -.
DR EvolutionaryTrace; Q57U83; -.
DR Proteomes; UP000008524; Chromosome 5.
DR GO; GO:0097014; C:ciliary plasm; IDA:GeneDB.
DR GO; GO:0005737; C:cytoplasm; IDA:GeneDB.
DR GO; GO:0020015; C:glycosome; ISO:GeneDB.
DR GO; GO:0005654; C:nucleoplasm; IDA:GeneDB.
DR GO; GO:1990663; F:dihydroorotate dehydrogenase (fumarate) activity; IEA:UniProtKB-EC.
DR GO; GO:0004152; F:dihydroorotate dehydrogenase activity; IBA:GO_Central.
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:0006106; P:fumarate metabolic process; ISO:GeneDB.
DR CDD; cd04741; DHOD_1A_like; 1.
DR Gene3D; 3.20.20.70; -; 1.
DR InterPro; IPR013785; Aldolase_TIM.
DR InterPro; IPR033886; DHOD_1A.
DR InterPro; IPR005720; Dihydroorotate_DH.
DR InterPro; IPR012135; Dihydroorotate_DH_1_2.
DR Pfam; PF01180; DHO_dh; 1.
DR PIRSF; PIRSF000164; DHO_oxidase; 1.
DR TIGRFAMs; TIGR01037; pyrD_sub1_fam; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; Flavoprotein; FMN; Oxidoreductase;
KW Pyrimidine biosynthesis; Reference proteome.
FT CHAIN 1..313
FT /note="Dihydroorotate dehydrogenase (fumarate)"
FT /id="PRO_0000409559"
FT ACT_SITE 131
FT /note="Nucleophile"
FT /evidence="ECO:0000250"
FT BINDING 20
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000269|PubMed:18312275"
FT BINDING 44..45
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000269|PubMed:18312275"
FT BINDING 44
FT /ligand="substrate"
FT BINDING 68..72
FT /ligand="substrate"
FT BINDING 128
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000269|PubMed:18312275"
FT BINDING 128
FT /ligand="substrate"
FT BINDING 133
FT /ligand="substrate"
FT BINDING 165
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000269|PubMed:18312275"
FT BINDING 194
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000269|PubMed:18312275"
FT BINDING 195..196
FT /ligand="substrate"
FT BINDING 223
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000269|PubMed:18312275"
FT BINDING 249..251
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000269|PubMed:18312275"
FT BINDING 249
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000269|PubMed:18312275"
FT BINDING 272..273
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000269|PubMed:18312275"
FT STRAND 5..7
FT /evidence="ECO:0007829|PDB:5XFW"
FT STRAND 10..18
FT /evidence="ECO:0007829|PDB:5XFW"
FT HELIX 27..35
FT /evidence="ECO:0007829|PDB:5XFW"
FT STRAND 41..46
FT /evidence="ECO:0007829|PDB:5XFW"
FT STRAND 59..62
FT /evidence="ECO:0007829|PDB:5XFW"
FT STRAND 65..68
FT /evidence="ECO:0007829|PDB:5XFW"
FT HELIX 77..86
FT /evidence="ECO:0007829|PDB:5XFW"
FT TURN 90..92
FT /evidence="ECO:0007829|PDB:5XFW"
FT STRAND 95..99
FT /evidence="ECO:0007829|PDB:5XFW"
FT HELIX 104..121
FT /evidence="ECO:0007829|PDB:5XFW"
FT STRAND 124..128
FT /evidence="ECO:0007829|PDB:5XFW"
FT HELIX 140..142
FT /evidence="ECO:0007829|PDB:5XFW"
FT HELIX 144..158
FT /evidence="ECO:0007829|PDB:5XFW"
FT STRAND 162..166
FT /evidence="ECO:0007829|PDB:5XFW"
FT HELIX 172..182
FT /evidence="ECO:0007829|PDB:5XFW"
FT STRAND 188..193
FT /evidence="ECO:0007829|PDB:5XFW"
FT STRAND 197..201
FT /evidence="ECO:0007829|PDB:5XFW"
FT TURN 205..208
FT /evidence="ECO:0007829|PDB:5XFW"
FT STRAND 209..211
FT /evidence="ECO:0007829|PDB:5XFW"
FT HELIX 214..217
FT /evidence="ECO:0007829|PDB:5XFW"
FT STRAND 218..223
FT /evidence="ECO:0007829|PDB:5XFW"
FT HELIX 224..226
FT /evidence="ECO:0007829|PDB:5XFW"
FT HELIX 227..240
FT /evidence="ECO:0007829|PDB:5XFW"
FT STRAND 244..250
FT /evidence="ECO:0007829|PDB:5XFW"
FT HELIX 255..264
FT /evidence="ECO:0007829|PDB:5XFW"
FT STRAND 266..271
FT /evidence="ECO:0007829|PDB:5XFW"
FT HELIX 273..278
FT /evidence="ECO:0007829|PDB:5XFW"
FT HELIX 282..297
FT /evidence="ECO:0007829|PDB:5XFW"
FT HELIX 302..304
FT /evidence="ECO:0007829|PDB:5XFW"
FT TURN 305..307
FT /evidence="ECO:0007829|PDB:5XFW"
SQ SEQUENCE 313 AA; 34112 MW; C005E7470D4C1EA1 CRC64;
MSLKVNILGH EFSNPFMNAA GVLCTTEEDL RRMTESESGS LIGKSCTLAP RTGNPEPRYF
GLPLGSINSM GLPNLGVDFY LSYAAQTHDY SRKPLFLSMS GLSVEESVEM VKKLAPITKE
KGTILELNLS CPNVPGKPQV GYDFDTTRTY LQKVSEAYGL PFGVKMPPYF DIAHFDMAAA
VLNDFPLVKF ITCVNSIGNG LVIDPANETV VIKPKQGFGG LGGKYVLPTA LANVNAFFRR
CPDKLVFGCG GVYSGEEAFL HILAGASMVQ VGTALHDEGP IIFARLNKEL QEIMTNKGYK
TLDEFRGRVK TMD
