PYRC_AQUAE
ID PYRC_AQUAE Reviewed; 422 AA.
AC O66990;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1998, sequence version 1.
DT 03-AUG-2022, entry version 147.
DE RecName: Full=Dihydroorotase {ECO:0000255|HAMAP-Rule:MF_00220};
DE Short=DHOase {ECO:0000255|HAMAP-Rule:MF_00220};
DE EC=3.5.2.3 {ECO:0000255|HAMAP-Rule:MF_00220, ECO:0000269|PubMed:15381710, ECO:0000269|PubMed:24314009};
GN Name=pyrC {ECO:0000255|HAMAP-Rule:MF_00220}; OrderedLocusNames=aq_806;
OS Aquifex aeolicus (strain VF5).
OC Bacteria; Aquificae; Aquificales; Aquificaceae; Aquifex.
OX NCBI_TaxID=224324;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=VF5;
RX PubMed=9537320; DOI=10.1038/32831;
RA Deckert G., Warren P.V., Gaasterland T., Young W.G., Lenox A.L.,
RA Graham D.E., Overbeek R., Snead M.A., Keller M., Aujay M., Huber R.,
RA Feldman R.A., Short J.M., Olsen G.J., Swanson R.V.;
RT "The complete genome of the hyperthermophilic bacterium Aquifex aeolicus.";
RL Nature 392:353-358(1998).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, ACTIVITY REGULATION, AND SUBUNIT.
RX PubMed=15381710; DOI=10.1074/jbc.m403009200;
RA Ahuja A., Purcarea C., Ebert R., Sadecki S., Guy H.I., Evans D.R.;
RT "Aquifex aeolicus dihydroorotase: association with aspartate
RT transcarbamoylase switches on catalytic activity.";
RL J. Biol. Chem. 279:53136-53144(2004).
RN [3] {ECO:0007744|PDB:1XRF, ECO:0007744|PDB:1XRT}
RP X-RAY CRYSTALLOGRAPHY (1.61 ANGSTROMS) IN COMPLEX WITH ZINC, AND COFACTOR.
RX PubMed=15826652; DOI=10.1016/j.jmb.2005.03.015;
RA Martin P.D., Purcarea C., Zhang P., Vaishnav A., Sadecki S.,
RA Guy-Evans H.I., Evans D.R., Edwards B.F.;
RT "The crystal structure of a novel, latent dihydroorotase from Aquifex
RT aeolicus at 1.7A resolution.";
RL J. Mol. Biol. 348:535-547(2005).
RN [4] {ECO:0007744|PDB:3D6N}
RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) IN COMPLEX WITH PYRB AND ZINC,
RP COFACTOR, AND SUBUNIT.
RX PubMed=19128030; DOI=10.1021/bi801831r;
RA Zhang P., Martin P.D., Purcarea C., Vaishnav A., Brunzelle J.S.,
RA Fernando R., Guy-Evans H.I., Evans D.R., Edwards B.F.;
RT "Dihydroorotase from the hyperthermophile Aquifex aeolicus is activated by
RT stoichiometric association with aspartate transcarbamoylase and forms a
RT one-pot reactor for pyrimidine biosynthesis.";
RL Biochemistry 48:766-778(2009).
RN [5] {ECO:0007744|PDB:4BJH}
RP X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) IN COMPLEX WITH PYRB; DIHYDROOROTIC
RP ACID AND ZINC, FUNCTION, CATALYTIC ACTIVITY, COFACTOR, AND MUTAGENESIS OF
RP HIS-180 AND HIS-232.
RX PubMed=24314009; DOI=10.1186/1471-2091-14-36;
RA Edwards B.F., Fernando R., Martin P.D., Grimley E., Cordes M., Vaishnav A.,
RA Brunzelle J.S., Evans H.G., Evans D.R.;
RT "The mononuclear metal center of type-I dihydroorotase from Aquifex
RT aeolicus.";
RL BMC Biochem. 14:36-36(2013).
CC -!- FUNCTION: Catalyzes the reversible cyclization of carbamoyl aspartate
CC to dihydroorotate. {ECO:0000255|HAMAP-Rule:MF_00220,
CC ECO:0000269|PubMed:15381710, ECO:0000269|PubMed:24314009}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(S)-dihydroorotate + H2O = H(+) + N-carbamoyl-L-aspartate;
CC Xref=Rhea:RHEA:24296, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30864, ChEBI:CHEBI:32814; EC=3.5.2.3;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_00220,
CC ECO:0000269|PubMed:15381710, ECO:0000269|PubMed:24314009};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_00220,
CC ECO:0000269|PubMed:15381710, ECO:0000269|PubMed:15826652,
CC ECO:0000269|PubMed:19128030, ECO:0000269|PubMed:24314009};
CC Note=Binds 1 Zn(2+) ion per subunit (PubMed:15381710, PubMed:15826652,
CC PubMed:19128030, PubMed:24314009). Fully functional with a mononuclear
CC metal center. Does not require a second metal for activity, although
CC the conservation of the second metal-binding site during evolution
CC leaves open the possibility that a second ion might bind in vivo
CC (PubMed:24314009). {ECO:0000269|PubMed:15381710,
CC ECO:0000269|PubMed:15826652, ECO:0000269|PubMed:19128030,
CC ECO:0000269|PubMed:24314009};
CC -!- ACTIVITY REGULATION: The monomer has very low activity by itself.
CC Activated several thousandfold by formation of a complex with PyrB
CC aspartate carbamoyltransferase (ATCase). {ECO:0000269|PubMed:15381710}.
CC -!- PATHWAY: Pyrimidine metabolism; UMP biosynthesis via de novo pathway;
CC (S)-dihydroorotate from bicarbonate: step 3/3. {ECO:0000255|HAMAP-
CC Rule:MF_00220, ECO:0000305}.
CC -!- SUBUNIT: Monomer. Forms a 1:1 stoichiometric complex with PyrB. The
CC complex exists as an equilibrium mixture of heterohexamers, composed of
CC 3 PyrC and 3 PyrB subunits, and dodecamers. The complex has both DHOase
CC and ATCase activities. {ECO:0000269|PubMed:15381710,
CC ECO:0000269|PubMed:19128030}.
CC -!- SIMILARITY: Belongs to the metallo-dependent hydrolases superfamily.
CC DHOase family. Class I DHOase subfamily. {ECO:0000255|HAMAP-
CC Rule:MF_00220, ECO:0000305}.
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DR EMBL; AE000657; AAC06948.1; -; Genomic_DNA.
DR PIR; C70370; C70370.
DR RefSeq; NP_213551.1; NC_000918.1.
DR RefSeq; WP_010880489.1; NC_000918.1.
DR PDB; 1XRF; X-ray; 1.65 A; A=1-422.
DR PDB; 1XRT; X-ray; 1.61 A; A/B=1-422.
DR PDB; 3D6N; X-ray; 2.30 A; A=1-422.
DR PDB; 4BJH; X-ray; 2.20 A; A=1-422.
DR PDB; 6GDD; X-ray; 2.60 A; A=1-422.
DR PDB; 6GDE; X-ray; 2.45 A; A=1-422.
DR PDB; 6GDF; X-ray; 2.50 A; A=1-422.
DR PDBsum; 1XRF; -.
DR PDBsum; 1XRT; -.
DR PDBsum; 3D6N; -.
DR PDBsum; 4BJH; -.
DR PDBsum; 6GDD; -.
DR PDBsum; 6GDE; -.
DR PDBsum; 6GDF; -.
DR AlphaFoldDB; O66990; -.
DR SMR; O66990; -.
DR STRING; 224324.aq_806; -.
DR EnsemblBacteria; AAC06948; AAC06948; aq_806.
DR KEGG; aae:aq_806; -.
DR PATRIC; fig|224324.8.peg.636; -.
DR eggNOG; COG0044; Bacteria.
DR HOGENOM; CLU_015572_1_0_0; -.
DR InParanoid; O66990; -.
DR OMA; QHAQEPR; -.
DR OrthoDB; 1319925at2; -.
DR BRENDA; 3.5.2.3; 396.
DR SABIO-RK; O66990; -.
DR UniPathway; UPA00070; UER00117.
DR EvolutionaryTrace; O66990; -.
DR Proteomes; UP000000798; Chromosome.
DR GO; GO:0004151; F:dihydroorotase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0008270; F:zinc ion binding; IEA:UniProtKB-UniRule.
DR GO; GO:0044205; P:'de novo' UMP biosynthetic process; IEA:UniProtKB-UniPathway.
DR CDD; cd01317; DHOase_IIa; 1.
DR Gene3D; 2.30.40.10; -; 1.
DR HAMAP; MF_00220_B; PyrC_classI_B; 1.
DR InterPro; IPR006680; Amidohydro-rel.
DR InterPro; IPR004722; DHOase.
DR InterPro; IPR002195; Dihydroorotase_CS.
DR InterPro; IPR011059; Metal-dep_hydrolase_composite.
DR InterPro; IPR032466; Metal_Hydrolase.
DR Pfam; PF01979; Amidohydro_1; 1.
DR SUPFAM; SSF51338; SSF51338; 1.
DR SUPFAM; SSF51556; SSF51556; 1.
DR PROSITE; PS00482; DIHYDROOROTASE_1; 1.
DR PROSITE; PS00483; DIHYDROOROTASE_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Hydrolase; Metal-binding; Pyrimidine biosynthesis;
KW Reference proteome; Zinc.
FT CHAIN 1..422
FT /note="Dihydroorotase"
FT /id="PRO_0000147226"
FT ACT_SITE 305
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00220"
FT BINDING 61
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:15826652,
FT ECO:0000269|PubMed:19128030, ECO:0000269|PubMed:24314009,
FT ECO:0007744|PDB:1XRF, ECO:0007744|PDB:1XRT,
FT ECO:0007744|PDB:3D6N, ECO:0007744|PDB:4BJH"
FT BINDING 63..65
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00220,
FT ECO:0000305|PubMed:24314009, ECO:0007744|PDB:4BJH"
FT BINDING 63
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:15826652,
FT ECO:0000269|PubMed:19128030, ECO:0000269|PubMed:24314009,
FT ECO:0007744|PDB:1XRF, ECO:0007744|PDB:1XRT,
FT ECO:0007744|PDB:3D6N, ECO:0007744|PDB:4BJH"
FT BINDING 95
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00220,
FT ECO:0000305|PubMed:24314009, ECO:0007744|PDB:4BJH"
FT BINDING 153
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:15826652,
FT ECO:0000269|PubMed:19128030, ECO:0000269|PubMed:24314009,
FT ECO:0007744|PDB:1XRF, ECO:0007744|PDB:1XRT,
FT ECO:0007744|PDB:3D6N, ECO:0007744|PDB:4BJH"
FT BINDING 278
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00220,
FT ECO:0000305|PubMed:24314009, ECO:0007744|PDB:4BJH"
FT BINDING 305
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:19128030,
FT ECO:0000269|PubMed:24314009, ECO:0007744|PDB:3D6N,
FT ECO:0007744|PDB:4BJH"
FT BINDING 309
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00220,
FT ECO:0000305|PubMed:24314009, ECO:0007744|PDB:4BJH"
FT BINDING 322..323
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00220,
FT ECO:0000305|PubMed:24314009, ECO:0007744|PDB:4BJH"
FT MUTAGEN 180
FT /note="H->A: Does not affect activity."
FT /evidence="ECO:0000269|PubMed:24314009"
FT MUTAGEN 232
FT /note="H->A: Does not affect activity."
FT /evidence="ECO:0000269|PubMed:24314009"
FT STRAND 3..8
FT /evidence="ECO:0007829|PDB:1XRT"
FT STRAND 10..13
FT /evidence="ECO:0007829|PDB:1XRT"
FT HELIX 14..16
FT /evidence="ECO:0007829|PDB:1XRT"
FT STRAND 18..21
FT /evidence="ECO:0007829|PDB:1XRT"
FT STRAND 23..27
FT /evidence="ECO:0007829|PDB:1XRT"
FT STRAND 30..37
FT /evidence="ECO:0007829|PDB:1XRT"
FT STRAND 41..47
FT /evidence="ECO:0007829|PDB:1XRT"
FT STRAND 51..55
FT /evidence="ECO:0007829|PDB:1XRT"
FT STRAND 57..62
FT /evidence="ECO:0007829|PDB:1XRT"
FT TURN 66..68
FT /evidence="ECO:0007829|PDB:1XRT"
FT TURN 70..72
FT /evidence="ECO:0007829|PDB:1XRT"
FT HELIX 75..84
FT /evidence="ECO:0007829|PDB:1XRT"
FT STRAND 87..92
FT /evidence="ECO:0007829|PDB:1XRT"
FT STRAND 96..98
FT /evidence="ECO:0007829|PDB:1XRT"
FT HELIX 103..116
FT /evidence="ECO:0007829|PDB:1XRT"
FT STRAND 118..123
FT /evidence="ECO:0007829|PDB:1XRT"
FT HELIX 129..131
FT /evidence="ECO:0007829|PDB:1XRT"
FT STRAND 133..136
FT /evidence="ECO:0007829|PDB:1XRT"
FT HELIX 139..145
FT /evidence="ECO:0007829|PDB:1XRT"
FT HELIX 160..173
FT /evidence="ECO:0007829|PDB:1XRT"
FT STRAND 176..179
FT /evidence="ECO:0007829|PDB:1XRT"
FT HELIX 183..186
FT /evidence="ECO:0007829|PDB:1XRT"
FT STRAND 189..194
FT /evidence="ECO:0007829|PDB:4BJH"
FT HELIX 195..200
FT /evidence="ECO:0007829|PDB:4BJH"
FT HELIX 210..224
FT /evidence="ECO:0007829|PDB:1XRT"
FT STRAND 227..231
FT /evidence="ECO:0007829|PDB:1XRT"
FT HELIX 236..247
FT /evidence="ECO:0007829|PDB:1XRT"
FT STRAND 252..256
FT /evidence="ECO:0007829|PDB:1XRT"
FT HELIX 258..261
FT /evidence="ECO:0007829|PDB:1XRT"
FT HELIX 267..271
FT /evidence="ECO:0007829|PDB:4BJH"
FT HELIX 272..275
FT /evidence="ECO:0007829|PDB:4BJH"
FT HELIX 287..295
FT /evidence="ECO:0007829|PDB:1XRT"
FT HELIX 311..313
FT /evidence="ECO:0007829|PDB:4BJH"
FT STRAND 314..316
FT /evidence="ECO:0007829|PDB:4BJH"
FT HELIX 317..319
FT /evidence="ECO:0007829|PDB:4BJH"
FT HELIX 327..329
FT /evidence="ECO:0007829|PDB:1XRT"
FT HELIX 330..339
FT /evidence="ECO:0007829|PDB:1XRT"
FT HELIX 345..352
FT /evidence="ECO:0007829|PDB:1XRT"
FT HELIX 354..360
FT /evidence="ECO:0007829|PDB:1XRT"
FT STRAND 375..385
FT /evidence="ECO:0007829|PDB:1XRT"
FT TURN 388..390
FT /evidence="ECO:0007829|PDB:1XRT"
FT TURN 399..402
FT /evidence="ECO:0007829|PDB:1XRT"
FT STRAND 404..414
FT /evidence="ECO:0007829|PDB:1XRT"
FT STRAND 417..421
FT /evidence="ECO:0007829|PDB:1XRT"
SQ SEQUENCE 422 AA; 46380 MW; 7004E6A48B0165EB CRC64;
MLKLIVKNGY VIDPSQNLEG EFDILVENGK IKKIDKNILV PEAEIIDAKG LIVCPGFIDI
HVHLRDPGQT YKEDIESGSR CAVAGGFTTI VCMPNTNPPI DNTTVVNYIL QKSKSVGLCR
VLPTGTITKG RKGKEIADFY SLKEAGCVAF TDDGSPVMDS SVMRKALELA SQLGVPIMDH
CEDDKLAYGV INEGEVSALL GLSSRAPEAE EIQIARDGIL AQRTGGHVHI QHVSTKLSLE
IIEFFKEKGV KITCEVNPNH LLFTEREVLN SGANARVNPP LRKKEDRLAL IEGVKRGIID
CFATDHAPHQ TFEKELVEFA MPGIIGLQTA LPSALELYRK GIISLKKLIE MFTINPARII
GVDLGTLKLG SPADITIFDP NKEWILNEET NLSKSRNTPL WGKVLKGKVI YTIKDGKMVY
KD
