PYRD_TRYCC
ID PYRD_TRYCC Reviewed; 314 AA.
AC Q4D3W2; O76140;
DT 31-MAY-2011, integrated into UniProtKB/Swiss-Prot.
DT 13-SEP-2005, sequence version 1.
DT 03-AUG-2022, entry version 102.
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 Name=pyr4; Synonyms=tcdhod2; ORFNames=Tc00.1047053508375.50;
OS Trypanosoma cruzi (strain CL Brener).
OC Eukaryota; Discoba; Euglenozoa; Kinetoplastea; Metakinetoplastina;
OC Trypanosomatida; Trypanosomatidae; Trypanosoma; Schizotrypanum.
OX NCBI_TaxID=353153;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] (ALLELE DHOD1).
RC STRAIN=CL Brener;
RX PubMed=16020725; DOI=10.1126/science.1112631;
RA El-Sayed N.M.A., Myler P.J., Bartholomeu D.C., Nilsson D., Aggarwal G.,
RA Tran A.-N., Ghedin E., Worthey E.A., Delcher A.L., Blandin G.,
RA Westenberger S.J., Caler E., Cerqueira G.C., Branche C., Haas B.,
RA Anupama A., Arner E., Aslund L., Attipoe P., Bontempi E., Bringaud F.,
RA Burton P., Cadag E., Campbell D.A., Carrington M., Crabtree J., Darban H.,
RA da Silveira J.F., de Jong P., Edwards K., Englund P.T., Fazelina G.,
RA Feldblyum T., Ferella M., Frasch A.C., Gull K., Horn D., Hou L., Huang Y.,
RA Kindlund E., Klingbeil M., Kluge S., Koo H., Lacerda D., Levin M.J.,
RA Lorenzi H., Louie T., Machado C.R., McCulloch R., McKenna A., Mizuno Y.,
RA Mottram J.C., Nelson S., Ochaya S., Osoegawa K., Pai G., Parsons M.,
RA Pentony M., Pettersson U., Pop M., Ramirez J.L., Rinta J., Robertson L.,
RA Salzberg S.L., Sanchez D.O., Seyler A., Sharma R., Shetty J., Simpson A.J.,
RA Sisk E., Tammi M.T., Tarleton R., Teixeira S., Van Aken S., Vogt C.,
RA Ward P.N., Wickstead B., Wortman J., White O., Fraser C.M., Stuart K.D.,
RA Andersson B.;
RT "The genome sequence of Trypanosoma cruzi, etiologic agent of Chagas
RT disease.";
RL Science 309:409-415(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ALLELE DHOD1).
RC STRAIN=Tulahuen;
RX PubMed=9878395; DOI=10.1006/jmbi.1998.2293;
RA Gao G., Nara T., Nakajima-Shimada J., Aoki T.;
RT "Novel organization and sequences of five genes encoding all six enzymes
RT for de novo pyrimidine biosynthesis in Trypanosoma cruzi.";
RL J. Mol. Biol. 285:149-161(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ALLELES DHOD1; DHOD2 AND DHOD3), AND
RP BIOPHYSICOCHEMICAL PROPERTIES.
RC STRAIN=Tulahuen;
RX PubMed=16172019; DOI=10.1016/j.parint.2005.08.001;
RA Sariego I., Annoura T., Nara T., Hashimoto M., Tsubouchi A., Iizumi K.,
RA Makiuchi T., Murata E., Kita K., Aoki T.;
RT "Genetic diversity and kinetic properties of Trypanosoma cruzi
RT dihydroorotate dehydrogenase isoforms.";
RL Parasitol. Int. 55:11-16(2006).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (1.38 ANGSTROMS) OF APOENZYME AND IN COMPLEXES WITH
RP FMN; DIHYDROOROTATE; OROTATE; FUMARATE AND SUCCINATE, COFACTOR, AND
RP REACTION MECHANISM.
RC STRAIN=Tulahuen;
RX PubMed=18808149; DOI=10.1021/bi800413r;
RA Inaoka D.K., Sakamoto K., Shimizu H., Shiba T., Kurisu G., Nara T.,
RA Aoki T., Kita K., Harada S.;
RT "Structures of Trypanosoma cruzi dihydroorotate dehydrogenase complexed
RT with substrates and products: atomic resolution insights into mechanisms of
RT dihydroorotate oxidation and fumarate reduction.";
RL Biochemistry 47:10881-10891(2008).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 3-314 IN COMPLEX WITH FMN.
RC STRAIN=Y;
RX PubMed=18302934; DOI=10.1016/j.bbrc.2008.02.074;
RA Pinheiro M.P., Iulek J., Cristina Nonato M.;
RT "Crystal structure of Trypanosoma cruzi dihydroorotate dehydrogenase from Y
RT strain.";
RL Biochem. Biophys. Res. Commun. 369:812-817(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:18808149};
CC Note=Binds 1 FMN per subunit. {ECO:0000269|PubMed:18808149};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=57.3 uM for dihydroorotate {ECO:0000269|PubMed:16172019};
CC KM=62.2 uM for fumarate {ECO:0000269|PubMed:16172019};
CC pH dependence:
CC Optimum pH is 7. {ECO:0000269|PubMed:16172019};
CC Temperature dependence:
CC Optimum temperature is 37 degrees Celsius.
CC {ECO:0000269|PubMed:16172019};
CC -!- PATHWAY: Pyrimidine metabolism; UMP biosynthesis via de novo pathway.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:18302934}.
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; AAHK01001070; EAN87213.1; -; Genomic_DNA.
DR EMBL; AB010286; BAA31360.1; -; Genomic_DNA.
DR EMBL; AB017765; BAA74526.1; -; Genomic_DNA.
DR EMBL; AB212956; BAE48283.1; -; Genomic_DNA.
DR PIR; T30523; T30523.
DR RefSeq; XP_809064.1; XM_803971.1.
DR PDB; 2DJL; X-ray; 1.38 A; A/B=1-314.
DR PDB; 2DJX; X-ray; 1.58 A; A/B=1-314.
DR PDB; 2E68; X-ray; 1.38 A; A/B=1-314.
DR PDB; 2E6A; X-ray; 1.64 A; A/B=1-314.
DR PDB; 2E6D; X-ray; 1.94 A; A/B=1-314.
DR PDB; 2E6F; X-ray; 1.26 A; A/B=1-314.
DR PDB; 3C3N; X-ray; 2.20 A; A/B/C/D=3-314.
DR PDB; 3W1A; X-ray; 1.42 A; A/B=2-314.
DR PDB; 3W1L; X-ray; 1.70 A; A/B=2-314.
DR PDB; 3W1M; X-ray; 1.90 A; A/B=2-314.
DR PDB; 3W1N; X-ray; 2.40 A; A/B=2-314.
DR PDB; 3W1P; X-ray; 2.00 A; A/B=2-314.
DR PDB; 3W1Q; X-ray; 1.85 A; A/B=2-314.
DR PDB; 3W1R; X-ray; 1.58 A; A/B=2-314.
DR PDB; 3W1T; X-ray; 1.68 A; A/B=2-314.
DR PDB; 3W1U; X-ray; 1.85 A; A/B=2-314.
DR PDB; 3W1X; X-ray; 1.45 A; A/B=2-314.
DR PDB; 3W22; X-ray; 1.98 A; A/B=2-314.
DR PDB; 3W23; X-ray; 1.48 A; A/B=2-314.
DR PDB; 3W2J; X-ray; 1.42 A; A/B=2-314.
DR PDB; 3W2K; X-ray; 1.54 A; A/B=2-314.
DR PDB; 3W2L; X-ray; 1.64 A; A/B=2-314.
DR PDB; 3W2M; X-ray; 1.58 A; A/B=2-314.
DR PDB; 3W2N; X-ray; 1.96 A; A/B=2-314.
DR PDB; 3W2U; X-ray; 2.25 A; A/B=2-314.
DR PDB; 3W3O; X-ray; 1.96 A; A/B=2-314.
DR PDB; 3W6Y; X-ray; 2.68 A; A/B=2-314.
DR PDB; 3W70; X-ray; 2.60 A; A/B=2-314.
DR PDB; 3W71; X-ray; 1.68 A; A/B=2-314.
DR PDB; 3W72; X-ray; 1.55 A; A/B=2-314.
DR PDB; 3W73; X-ray; 1.78 A; A/B=2-314.
DR PDB; 3W74; X-ray; 1.90 A; A/B=2-314.
DR PDB; 3W75; X-ray; 1.47 A; A/B=2-314.
DR PDB; 3W76; X-ray; 1.58 A; A/B=2-314.
DR PDB; 3W7C; X-ray; 1.75 A; A/B=2-314.
DR PDB; 3W7D; X-ray; 1.52 A; A/B=2-314.
DR PDB; 3W7E; X-ray; 1.56 A; A/B=2-314.
DR PDB; 3W7G; X-ray; 1.55 A; A/B=2-314.
DR PDB; 3W7H; X-ray; 1.67 A; A/B=2-314.
DR PDB; 3W7I; X-ray; 1.69 A; A/B=2-314.
DR PDB; 3W7J; X-ray; 1.58 A; A/B=2-314.
DR PDB; 3W7K; X-ray; 1.61 A; A/B=2-314.
DR PDB; 3W7L; X-ray; 1.88 A; A/B=2-314.
DR PDB; 3W7M; X-ray; 2.40 A; A/B=2-314.
DR PDB; 3W7N; X-ray; 2.39 A; A/B=2-314.
DR PDB; 3W7O; X-ray; 1.68 A; A/B=2-314.
DR PDB; 3W7P; X-ray; 1.70 A; A/B=2-314.
DR PDB; 3W7Q; X-ray; 1.83 A; A/B=2-314.
DR PDB; 3W83; X-ray; 2.80 A; A/B=2-314.
DR PDB; 3W84; X-ray; 1.93 A; A/B=2-314.
DR PDB; 3W85; X-ray; 2.00 A; A/B=2-314.
DR PDB; 3W86; X-ray; 1.50 A; A/B=2-314.
DR PDB; 3W87; X-ray; 1.43 A; A/B=2-314.
DR PDB; 3W88; X-ray; 1.40 A; A/B=2-314.
DR PDB; 4JD4; X-ray; 1.51 A; A/B=2-314.
DR PDB; 4JDB; X-ray; 1.82 A; A/B=2-314.
DR PDB; 5E93; X-ray; 1.41 A; A/B=2-314.
DR PDB; 5EA9; X-ray; 1.71 A; A/B=2-314.
DR PDBsum; 2DJL; -.
DR PDBsum; 2DJX; -.
DR PDBsum; 2E68; -.
DR PDBsum; 2E6A; -.
DR PDBsum; 2E6D; -.
DR PDBsum; 2E6F; -.
DR PDBsum; 3C3N; -.
DR PDBsum; 3W1A; -.
DR PDBsum; 3W1L; -.
DR PDBsum; 3W1M; -.
DR PDBsum; 3W1N; -.
DR PDBsum; 3W1P; -.
DR PDBsum; 3W1Q; -.
DR PDBsum; 3W1R; -.
DR PDBsum; 3W1T; -.
DR PDBsum; 3W1U; -.
DR PDBsum; 3W1X; -.
DR PDBsum; 3W22; -.
DR PDBsum; 3W23; -.
DR PDBsum; 3W2J; -.
DR PDBsum; 3W2K; -.
DR PDBsum; 3W2L; -.
DR PDBsum; 3W2M; -.
DR PDBsum; 3W2N; -.
DR PDBsum; 3W2U; -.
DR PDBsum; 3W3O; -.
DR PDBsum; 3W6Y; -.
DR PDBsum; 3W70; -.
DR PDBsum; 3W71; -.
DR PDBsum; 3W72; -.
DR PDBsum; 3W73; -.
DR PDBsum; 3W74; -.
DR PDBsum; 3W75; -.
DR PDBsum; 3W76; -.
DR PDBsum; 3W7C; -.
DR PDBsum; 3W7D; -.
DR PDBsum; 3W7E; -.
DR PDBsum; 3W7G; -.
DR PDBsum; 3W7H; -.
DR PDBsum; 3W7I; -.
DR PDBsum; 3W7J; -.
DR PDBsum; 3W7K; -.
DR PDBsum; 3W7L; -.
DR PDBsum; 3W7M; -.
DR PDBsum; 3W7N; -.
DR PDBsum; 3W7O; -.
DR PDBsum; 3W7P; -.
DR PDBsum; 3W7Q; -.
DR PDBsum; 3W83; -.
DR PDBsum; 3W84; -.
DR PDBsum; 3W85; -.
DR PDBsum; 3W86; -.
DR PDBsum; 3W87; -.
DR PDBsum; 3W88; -.
DR PDBsum; 4JD4; -.
DR PDBsum; 4JDB; -.
DR PDBsum; 5E93; -.
DR PDBsum; 5EA9; -.
DR AlphaFoldDB; Q4D3W2; -.
DR SMR; Q4D3W2; -.
DR STRING; 5693.XP_809064.1; -.
DR PaxDb; Q4D3W2; -.
DR EnsemblProtists; EAN87213; EAN87213; Tc00.1047053508375.50.
DR GeneID; 3539620; -.
DR KEGG; tcr:508375.50; -.
DR eggNOG; KOG1436; Eukaryota.
DR OMA; SCPHAKG; -.
DR OrthoDB; 1194348at2759; -.
DR BioCyc; MetaCyc:MON-14470; -.
DR BRENDA; 1.3.98.1; 6524.
DR UniPathway; UPA00070; -.
DR EvolutionaryTrace; Q4D3W2; -.
DR PHI-base; PHI:2575; -.
DR PHI-base; PHI:2596; -.
DR Proteomes; UP000002296; Unassembled WGS sequence.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:1990663; F:dihydroorotate dehydrogenase (fumarate) activity; IEA:UniProtKB-EC.
DR GO; GO:0044205; P:'de novo' UMP biosynthetic process; IEA:UniProtKB-UniPathway.
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..314
FT /note="Dihydroorotate dehydrogenase (fumarate)"
FT /id="PRO_0000409558"
FT ACT_SITE 132
FT /note="Nucleophile"
FT /evidence="ECO:0000250"
FT BINDING 21
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000269|PubMed:18302934"
FT BINDING 45..46
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000269|PubMed:18302934"
FT BINDING 45
FT /ligand="substrate"
FT BINDING 69..73
FT /ligand="substrate"
FT BINDING 129
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000269|PubMed:18302934"
FT BINDING 129
FT /ligand="substrate"
FT BINDING 134
FT /ligand="substrate"
FT BINDING 166
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000269|PubMed:18302934"
FT BINDING 195
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000269|PubMed:18302934"
FT BINDING 196..197
FT /ligand="substrate"
FT BINDING 224
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000269|PubMed:18302934"
FT BINDING 251..252
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000269|PubMed:18302934"
FT BINDING 273..274
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000269|PubMed:18302934"
FT VARIANT 2
FT /note="M -> T (in allele DHOD3)"
FT VARIANT 3
FT /note="C -> R (in alleles DHOD2 and DHOD3)"
FT VARIANT 63
FT /note="F -> V (in allele DHOD2)"
FT VARIANT 86
FT /note="S -> I (in alleles DHOD2 and DHOD3)"
FT VARIANT 98
FT /note="L -> V (in allele DHOD3)"
FT VARIANT 222
FT /note="L -> I (in alleles DHOD2 and DHOD3)"
FT VARIANT 285
FT /note="T -> R (in allele DHOD3)"
FT VARIANT 301
FT /note="R -> K (in allele DHOD2)"
FT CONFLICT 121
FT /note="E -> G (in Ref. 1; BAA74526/BAA31360)"
FT /evidence="ECO:0000305"
FT CONFLICT 141
FT /note="V -> G (in Ref. 1; BAA74526/BAA31360)"
FT /evidence="ECO:0000305"
FT STRAND 6..8
FT /evidence="ECO:0007829|PDB:2E6F"
FT STRAND 11..19
FT /evidence="ECO:0007829|PDB:2E6F"
FT HELIX 28..36
FT /evidence="ECO:0007829|PDB:2E6F"
FT STRAND 40..43
FT /evidence="ECO:0007829|PDB:2DJL"
FT STRAND 60..63
FT /evidence="ECO:0007829|PDB:2E6F"
FT STRAND 66..69
FT /evidence="ECO:0007829|PDB:2E6F"
FT HELIX 78..87
FT /evidence="ECO:0007829|PDB:2E6F"
FT TURN 91..93
FT /evidence="ECO:0007829|PDB:2E6F"
FT STRAND 96..100
FT /evidence="ECO:0007829|PDB:2E6F"
FT HELIX 105..122
FT /evidence="ECO:0007829|PDB:2E6F"
FT STRAND 125..129
FT /evidence="ECO:0007829|PDB:2E6F"
FT HELIX 141..143
FT /evidence="ECO:0007829|PDB:2E6F"
FT HELIX 145..159
FT /evidence="ECO:0007829|PDB:2E6F"
FT STRAND 163..167
FT /evidence="ECO:0007829|PDB:2E6F"
FT HELIX 173..184
FT /evidence="ECO:0007829|PDB:2E6F"
FT STRAND 189..194
FT /evidence="ECO:0007829|PDB:2E6F"
FT STRAND 198..202
FT /evidence="ECO:0007829|PDB:2E6F"
FT TURN 206..209
FT /evidence="ECO:0007829|PDB:2E6F"
FT STRAND 210..212
FT /evidence="ECO:0007829|PDB:2E6F"
FT HELIX 215..218
FT /evidence="ECO:0007829|PDB:2E6F"
FT STRAND 219..224
FT /evidence="ECO:0007829|PDB:2E6F"
FT HELIX 225..227
FT /evidence="ECO:0007829|PDB:2E6F"
FT HELIX 228..241
FT /evidence="ECO:0007829|PDB:2E6F"
FT STRAND 245..252
FT /evidence="ECO:0007829|PDB:2E6F"
FT HELIX 256..265
FT /evidence="ECO:0007829|PDB:2E6F"
FT STRAND 268..272
FT /evidence="ECO:0007829|PDB:2E6F"
FT HELIX 274..279
FT /evidence="ECO:0007829|PDB:2E6F"
FT HELIX 283..298
FT /evidence="ECO:0007829|PDB:2E6F"
FT TURN 304..308
FT /evidence="ECO:0007829|PDB:2E6F"
SQ SEQUENCE 314 AA; 34167 MW; 86917A54E3CD11FD CRC64;
MMCLKLNLLD HVFANPFMNA AGVLCSTEED LRCMTASSSG ALVSKSCTSA PRDGNPEPRY
MAFPLGSINS MGLPNLGFDF YLKYASDLHD YSKKPLFLSI SGLSVEENVA MVRRLAPVAQ
EKGVLLELNL SCPNVPGKPQ VAYDFEAMRT YLQQVSLAYG LPFGVKMPPY FDIAHFDTAA
AVLNEFPLVK FVTCVNSVGN GLVIDAESES VVIKPKQGFG GLGGKYILPT ALANVNAFYR
RCPDKLVFGC GGVYSGEDAF LHILAGASMV QVGTALQEEG PGIFTRLEDE LLEIMARKGY
RTLEEFRGRV KTIE
