PYRD_MYCTU
ID PYRD_MYCTU Reviewed; 357 AA.
AC P9WHL1; L0T8R3; O06236; P65908;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 40.
DE RecName: Full=Dihydroorotate dehydrogenase (quinone);
DE EC=1.3.5.2;
DE AltName: Full=DHOdehase;
DE Short=DHOD;
DE Short=DHODase;
DE AltName: Full=Dihydroorotate oxidase;
GN Name=pyrD; OrderedLocusNames=Rv2139; ORFNames=MTCY270.29c;
OS Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycobacterium; Mycobacterium tuberculosis complex.
OX NCBI_TaxID=83332;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=9634230; DOI=10.1038/31159;
RA Cole S.T., Brosch R., Parkhill J., Garnier T., Churcher C.M., Harris D.E.,
RA Gordon S.V., Eiglmeier K., Gas S., Barry C.E. III, Tekaia F., Badcock K.,
RA Basham D., Brown D., Chillingworth T., Connor R., Davies R.M., Devlin K.,
RA Feltwell T., Gentles S., Hamlin N., Holroyd S., Hornsby T., Jagels K.,
RA Krogh A., McLean J., Moule S., Murphy L.D., Oliver S., Osborne J.,
RA Quail M.A., Rajandream M.A., Rogers J., Rutter S., Seeger K., Skelton S.,
RA Squares S., Squares R., Sulston J.E., Taylor K., Whitehead S.,
RA Barrell B.G.;
RT "Deciphering the biology of Mycobacterium tuberculosis from the complete
RT genome sequence.";
RL Nature 393:537-544(1998).
RN [2]
RP IDENTIFICATION AS A DRUG TARGET [LARGE SCALE ANALYSIS].
RX PubMed=19099550; DOI=10.1186/1752-0509-2-109;
RA Raman K., Yeturu K., Chandra N.;
RT "targetTB: a target identification pipeline for Mycobacterium tuberculosis
RT through an interactome, reactome and genome-scale structural analysis.";
RL BMC Syst. Biol. 2:109-109(2008).
RN [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=21969609; DOI=10.1074/mcp.m111.011627;
RA Kelkar D.S., Kumar D., Kumar P., Balakrishnan L., Muthusamy B., Yadav A.K.,
RA Shrivastava P., Marimuthu A., Anand S., Sundaram H., Kingsbury R.,
RA Harsha H.C., Nair B., Prasad T.S., Chauhan D.S., Katoch K., Katoch V.M.,
RA Kumar P., Chaerkady R., Ramachandran S., Dash D., Pandey A.;
RT "Proteogenomic analysis of Mycobacterium tuberculosis by high resolution
RT mass spectrometry.";
RL Mol. Cell. Proteomics 10:M111.011627-M111.011627(2011).
CC -!- FUNCTION: Catalyzes the conversion of dihydroorotate to orotate with
CC quinone as electron acceptor. {ECO:0000250}.
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 -!- PATHWAY: Pyrimidine metabolism; UMP biosynthesis via de novo pathway;
CC orotate from (S)-dihydroorotate (quinone route): step 1/1.
CC -!- SUBUNIT: Monomer. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Peripheral membrane
CC protein {ECO:0000250}.
CC -!- MISCELLANEOUS: Was identified as a high-confidence drug target.
CC -!- SIMILARITY: Belongs to the dihydroorotate dehydrogenase family. Type 2
CC subfamily. {ECO:0000305}.
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DR EMBL; AL123456; CCP44914.1; -; Genomic_DNA.
DR PIR; G70577; G70577.
DR RefSeq; NP_216655.1; NC_000962.3.
DR RefSeq; WP_003411116.1; NZ_NVQJ01000044.1.
DR PDB; 4XQ6; X-ray; 2.00 A; A/B=31-353.
DR PDBsum; 4XQ6; -.
DR AlphaFoldDB; P9WHL1; -.
DR SMR; P9WHL1; -.
DR STRING; 83332.Rv2139; -.
DR PaxDb; P9WHL1; -.
DR DNASU; 887326; -.
DR GeneID; 887326; -.
DR KEGG; mtu:Rv2139; -.
DR TubercuList; Rv2139; -.
DR eggNOG; COG0167; Bacteria.
DR OMA; ERIKMGA; -.
DR PhylomeDB; P9WHL1; -.
DR UniPathway; UPA00070; UER00946.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005737; C:cytoplasm; IEA:InterPro.
DR GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
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:0009220; P:pyrimidine ribonucleotide biosynthetic process; IBA:GO_Central.
DR CDD; cd04738; DHOD_2_like; 1.
DR Gene3D; 3.20.20.70; -; 1.
DR HAMAP; MF_00225; DHO_dh_type2; 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 3D-structure; Cell membrane; Flavoprotein; FMN; Membrane; Oxidoreductase;
KW Pyrimidine biosynthesis; Reference proteome.
FT CHAIN 1..357
FT /note="Dihydroorotate dehydrogenase (quinone)"
FT /id="PRO_0000148457"
FT ACT_SITE 179
FT /note="Nucleophile"
FT /evidence="ECO:0000250"
FT BINDING 66..70
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250"
FT BINDING 70
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 90
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250"
FT BINDING 115..119
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 143
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250"
FT BINDING 176
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250"
FT BINDING 176
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 181
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 212
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250"
FT BINDING 240
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250"
FT BINDING 241..242
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 264
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250"
FT BINDING 293
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250"
FT BINDING 314..315
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250"
FT HELIX 32..42
FT /evidence="ECO:0007829|PDB:4XQ6"
FT HELIX 47..49
FT /evidence="ECO:0007829|PDB:4XQ6"
FT STRAND 51..53
FT /evidence="ECO:0007829|PDB:4XQ6"
FT STRAND 56..64
FT /evidence="ECO:0007829|PDB:4XQ6"
FT STRAND 68..74
FT /evidence="ECO:0007829|PDB:4XQ6"
FT HELIX 75..77
FT /evidence="ECO:0007829|PDB:4XQ6"
FT TURN 78..82
FT /evidence="ECO:0007829|PDB:4XQ6"
FT STRAND 86..94
FT /evidence="ECO:0007829|PDB:4XQ6"
FT STRAND 105..107
FT /evidence="ECO:0007829|PDB:4XQ6"
FT HELIX 108..110
FT /evidence="ECO:0007829|PDB:4XQ6"
FT STRAND 112..115
FT /evidence="ECO:0007829|PDB:4XQ6"
FT HELIX 124..132
FT /evidence="ECO:0007829|PDB:4XQ6"
FT STRAND 140..145
FT /evidence="ECO:0007829|PDB:4XQ6"
FT HELIX 152..154
FT /evidence="ECO:0007829|PDB:4XQ6"
FT HELIX 155..166
FT /evidence="ECO:0007829|PDB:4XQ6"
FT TURN 167..169
FT /evidence="ECO:0007829|PDB:4XQ6"
FT STRAND 171..176
FT /evidence="ECO:0007829|PDB:4XQ6"
FT HELIX 185..189
FT /evidence="ECO:0007829|PDB:4XQ6"
FT HELIX 191..204
FT /evidence="ECO:0007829|PDB:4XQ6"
FT STRAND 209..213
FT /evidence="ECO:0007829|PDB:4XQ6"
FT HELIX 219..231
FT /evidence="ECO:0007829|PDB:4XQ6"
FT STRAND 236..239
FT /evidence="ECO:0007829|PDB:4XQ6"
FT STRAND 261..264
FT /evidence="ECO:0007829|PDB:4XQ6"
FT HELIX 265..267
FT /evidence="ECO:0007829|PDB:4XQ6"
FT HELIX 268..282
FT /evidence="ECO:0007829|PDB:4XQ6"
FT TURN 283..285
FT /evidence="ECO:0007829|PDB:4XQ6"
FT STRAND 286..293
FT /evidence="ECO:0007829|PDB:4XQ6"
FT HELIX 297..305
FT /evidence="ECO:0007829|PDB:4XQ6"
FT STRAND 309..314
FT /evidence="ECO:0007829|PDB:4XQ6"
FT HELIX 315..320
FT /evidence="ECO:0007829|PDB:4XQ6"
FT HELIX 323..338
FT /evidence="ECO:0007829|PDB:4XQ6"
FT HELIX 344..347
FT /evidence="ECO:0007829|PDB:4XQ6"
FT HELIX 350..352
FT /evidence="ECO:0007829|PDB:4XQ6"
SQ SEQUENCE 357 AA; 37999 MW; 3D9D107DD9B4FCB6 CRC64;
MYPLVRRLLF LIPPEHAHKL VFAVLRGVAA VAPVRRLLRR LLGPTDPVLA STVFGVRFPA
PLGLAAGFDK DGTALSSWGA MGFGYAEIGT VTAHPQPGNP APRLFRLADD RALLNRMGFN
NHGARALAIR LARHRPEIPI GVNIGKTKKT PAGDAVNDYR ASARMVGPLA SYLVVNVSSP
NTPGLRDLQA VESLRPILSA VRAETSTPVL VKIAPDLSDS DLDDIADLAV ELDLAGIVAT
NTTVSRDGLT TPGVDRLGPG GISGPPLAQR AVQVLRRLYD RVGDRLALIS VGGIETADDA
WERITAGASL LQGYTGFIYG GERWAKDIHE GIARRLHDGG FGSLHEAVGS ARRRQPS
