PYRC_BACAN
ID PYRC_BACAN Reviewed; 428 AA.
AC Q81WF0; Q6HUJ8; Q6KNT3;
DT 18-MAR-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 1.
DT 03-AUG-2022, entry version 134.
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:27499369};
GN Name=pyrC {ECO:0000255|HAMAP-Rule:MF_00220};
GN OrderedLocusNames=BA_4027, GBAA_4027, BAS3739;
OS Bacillus anthracis.
OC Bacteria; Firmicutes; Bacilli; Bacillales; Bacillaceae; Bacillus;
OC Bacillus cereus group.
OX NCBI_TaxID=1392;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Ames / isolate Porton;
RX PubMed=12721629; DOI=10.1038/nature01586;
RA Read T.D., Peterson S.N., Tourasse N.J., Baillie L.W., Paulsen I.T.,
RA Nelson K.E., Tettelin H., Fouts D.E., Eisen J.A., Gill S.R.,
RA Holtzapple E.K., Okstad O.A., Helgason E., Rilstone J., Wu M.,
RA Kolonay J.F., Beanan M.J., Dodson R.J., Brinkac L.M., Gwinn M.L.,
RA DeBoy R.T., Madpu R., Daugherty S.C., Durkin A.S., Haft D.H., Nelson W.C.,
RA Peterson J.D., Pop M., Khouri H.M., Radune D., Benton J.L., Mahamoud Y.,
RA Jiang L., Hance I.R., Weidman J.F., Berry K.J., Plaut R.D., Wolf A.M.,
RA Watkins K.L., Nierman W.C., Hazen A., Cline R.T., Redmond C., Thwaite J.E.,
RA White O., Salzberg S.L., Thomason B., Friedlander A.M., Koehler T.M.,
RA Hanna P.C., Kolstoe A.-B., Fraser C.M.;
RT "The genome sequence of Bacillus anthracis Ames and comparison to closely
RT related bacteria.";
RL Nature 423:81-86(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Sterne;
RA Brettin T.S., Bruce D., Challacombe J.F., Gilna P., Han C., Hill K.,
RA Hitchcock P., Jackson P., Keim P., Longmire J., Lucas S., Okinaka R.,
RA Richardson P., Rubin E., Tice H.;
RT "Complete genome sequence of Bacillus anthracis Sterne.";
RL Submitted (JAN-2004) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Ames ancestor;
RX PubMed=18952800; DOI=10.1128/jb.01347-08;
RA Ravel J., Jiang L., Stanley S.T., Wilson M.R., Decker R.S., Read T.D.,
RA Worsham P., Keim P.S., Salzberg S.L., Fraser-Liggett C.M., Rasko D.A.;
RT "The complete genome sequence of Bacillus anthracis Ames 'Ancestor'.";
RL J. Bacteriol. 191:445-446(2009).
RN [4] {ECO:0007744|PDB:3MPG}
RP X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) IN COMPLEX WITH ZINC, COFACTOR, AND
RP SUBUNIT.
RC STRAIN=Sterne;
RX PubMed=21045288; DOI=10.1107/s1744309110037085;
RA Mehboob S., Mulhearn D.C., Truong K., Johnson M.E., Santarsiero B.D.;
RT "Structure of dihydroorotase from Bacillus anthracis at 2.6A resolution.";
RL Acta Crystallogr. F 66:1432-1435(2010).
RN [5] {ECO:0007744|PDB:4YIW}
RP X-RAY CRYSTALLOGRAPHY (2.45 ANGSTROMS) IN COMPLEX WITH CARBAMOYL ASPARTATE
RP AND ZINC, FUNCTION, CATALYTIC ACTIVITY, COFACTOR, BIOPHYSICOCHEMICAL
RP PROPERTIES, SUBUNIT, ACTIVE SITE, AND MUTAGENESIS OF ARG-63; ASN-93 AND
RP ASP-304.
RC STRAIN=Sterne;
RX PubMed=27499369; DOI=10.1016/j.bmc.2016.07.055;
RA Rice A.J., Lei H., Santarsiero B.D., Lee H., Johnson M.E.;
RT "Ca-asp bound X-ray structure and inhibition of Bacillus anthracis
RT dihydroorotase (DHOase).";
RL Bioorg. Med. Chem. 24:4536-4543(2016).
CC -!- FUNCTION: Catalyzes the reversible cyclization of carbamoyl aspartate
CC to dihydroorotate. {ECO:0000255|HAMAP-Rule:MF_00220,
CC ECO:0000269|PubMed:27499369}.
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:27499369};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_00220,
CC ECO:0000269|PubMed:21045288, ECO:0000269|PubMed:27499369};
CC Note=Binds 2 Zn(2+) ions per subunit. {ECO:0000255|HAMAP-Rule:MF_00220,
CC ECO:0000269|PubMed:21045288, ECO:0000269|PubMed:27499369};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=114 uM for dihydroorotate {ECO:0000269|PubMed:27499369};
CC KM=112 uM for carbamoyl aspartate {ECO:0000269|PubMed:27499369};
CC Note=kcat is 1.9 sec(-1) with dihydroorotate as substrate. kcat is
CC 2.1 sec(-1) with carbamoyl aspartate as substrate.
CC {ECO:0000269|PubMed:27499369};
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}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:21045288,
CC ECO:0000269|PubMed:27499369}.
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; AE016879; AAP27754.1; -; Genomic_DNA.
DR EMBL; AE017334; AAT33144.1; -; Genomic_DNA.
DR EMBL; AE017225; AAT56041.1; -; Genomic_DNA.
DR RefSeq; NP_846268.1; NC_003997.3.
DR RefSeq; WP_001108379.1; NZ_WXXJ01000026.1.
DR RefSeq; YP_029990.1; NC_005945.1.
DR PDB; 3MPG; X-ray; 2.60 A; A/B=1-428.
DR PDB; 4YIW; X-ray; 2.45 A; A/B=1-428.
DR PDBsum; 3MPG; -.
DR PDBsum; 4YIW; -.
DR AlphaFoldDB; Q81WF0; -.
DR SMR; Q81WF0; -.
DR IntAct; Q81WF0; 2.
DR STRING; 260799.BAS3739; -.
DR BindingDB; Q81WF0; -.
DR ChEMBL; CHEMBL3102690; -.
DR DNASU; 1086660; -.
DR EnsemblBacteria; AAP27754; AAP27754; BA_4027.
DR EnsemblBacteria; AAT33144; AAT33144; GBAA_4027.
DR GeneID; 45023717; -.
DR KEGG; ban:BA_4027; -.
DR KEGG; bar:GBAA_4027; -.
DR KEGG; bat:BAS3739; -.
DR PATRIC; fig|198094.11.peg.3998; -.
DR eggNOG; COG0044; Bacteria.
DR HOGENOM; CLU_015572_1_0_9; -.
DR OMA; QHAQEPR; -.
DR BRENDA; 3.5.2.3; 634.
DR UniPathway; UPA00070; UER00117.
DR Proteomes; UP000000427; Chromosome.
DR Proteomes; UP000000594; 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; -; 2.
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..428
FT /note="Dihydroorotase"
FT /id="PRO_0000325582"
FT ACT_SITE 304
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00220,
FT ECO:0000305|PubMed:27499369"
FT BINDING 59
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00220,
FT ECO:0000269|PubMed:21045288, ECO:0000269|PubMed:27499369,
FT ECO:0007744|PDB:3MPG, ECO:0007744|PDB:4YIW"
FT BINDING 61..63
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00220,
FT ECO:0000305|PubMed:27499369"
FT BINDING 61
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00220,
FT ECO:0000269|PubMed:21045288, ECO:0000269|PubMed:27499369,
FT ECO:0007744|PDB:3MPG, ECO:0007744|PDB:4YIW"
FT BINDING 93
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00220,
FT ECO:0000305|PubMed:27499369"
FT BINDING 151
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00220,
FT ECO:0000269|PubMed:21045288, ECO:0000269|PubMed:27499369,
FT ECO:0007744|PDB:3MPG, ECO:0007744|PDB:4YIW"
FT BINDING 151
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00220,
FT ECO:0000269|PubMed:21045288, ECO:0000269|PubMed:27499369,
FT ECO:0007744|PDB:3MPG, ECO:0007744|PDB:4YIW"
FT BINDING 178
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00220,
FT ECO:0000269|PubMed:21045288, ECO:0000269|PubMed:27499369,
FT ECO:0007744|PDB:3MPG, ECO:0007744|PDB:4YIW"
FT BINDING 231
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00220,
FT ECO:0000269|PubMed:21045288, ECO:0000269|PubMed:27499369,
FT ECO:0007744|PDB:3MPG, ECO:0007744|PDB:4YIW"
FT BINDING 277
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00220,
FT ECO:0000305|PubMed:27499369"
FT BINDING 304
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:27499369"
FT BINDING 304
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00220,
FT ECO:0000269|PubMed:21045288, ECO:0000269|PubMed:27499369,
FT ECO:0007744|PDB:3MPG, ECO:0007744|PDB:4YIW"
FT BINDING 308
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00220,
FT ECO:0000305|PubMed:27499369"
FT BINDING 322..323
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00220,
FT ECO:0000305|PubMed:27499369"
FT MUTAGEN 63
FT /note="R->A: Lack of activity."
FT /evidence="ECO:0000269|PubMed:27499369"
FT MUTAGEN 93
FT /note="N->A: Decreases activity with carbamoyl aspartate.
FT Lack of activity with dihydroorotate."
FT /evidence="ECO:0000269|PubMed:27499369"
FT MUTAGEN 304
FT /note="D->A: Lack of activity."
FT /evidence="ECO:0000269|PubMed:27499369"
FT STRAND 3..11
FT /evidence="ECO:0007829|PDB:4YIW"
FT STRAND 13..15
FT /evidence="ECO:0007829|PDB:4YIW"
FT STRAND 17..25
FT /evidence="ECO:0007829|PDB:4YIW"
FT STRAND 28..31
FT /evidence="ECO:0007829|PDB:4YIW"
FT STRAND 41..45
FT /evidence="ECO:0007829|PDB:4YIW"
FT STRAND 50..53
FT /evidence="ECO:0007829|PDB:4YIW"
FT STRAND 55..60
FT /evidence="ECO:0007829|PDB:4YIW"
FT TURN 64..66
FT /evidence="ECO:0007829|PDB:4YIW"
FT TURN 68..70
FT /evidence="ECO:0007829|PDB:4YIW"
FT HELIX 73..83
FT /evidence="ECO:0007829|PDB:4YIW"
FT STRAND 85..90
FT /evidence="ECO:0007829|PDB:4YIW"
FT STRAND 94..96
FT /evidence="ECO:0007829|PDB:4YIW"
FT HELIX 101..114
FT /evidence="ECO:0007829|PDB:4YIW"
FT STRAND 116..119
FT /evidence="ECO:0007829|PDB:4YIW"
FT STRAND 123..126
FT /evidence="ECO:0007829|PDB:3MPG"
FT HELIX 127..129
FT /evidence="ECO:0007829|PDB:4YIW"
FT STRAND 131..134
FT /evidence="ECO:0007829|PDB:4YIW"
FT HELIX 137..142
FT /evidence="ECO:0007829|PDB:4YIW"
FT HELIX 158..170
FT /evidence="ECO:0007829|PDB:4YIW"
FT STRAND 175..177
FT /evidence="ECO:0007829|PDB:4YIW"
FT HELIX 182..184
FT /evidence="ECO:0007829|PDB:4YIW"
FT STRAND 189..193
FT /evidence="ECO:0007829|PDB:4YIW"
FT HELIX 194..199
FT /evidence="ECO:0007829|PDB:4YIW"
FT HELIX 207..222
FT /evidence="ECO:0007829|PDB:4YIW"
FT STRAND 227..229
FT /evidence="ECO:0007829|PDB:4YIW"
FT HELIX 235..247
FT /evidence="ECO:0007829|PDB:4YIW"
FT STRAND 251..255
FT /evidence="ECO:0007829|PDB:4YIW"
FT HELIX 257..261
FT /evidence="ECO:0007829|PDB:4YIW"
FT HELIX 264..266
FT /evidence="ECO:0007829|PDB:4YIW"
FT HELIX 272..274
FT /evidence="ECO:0007829|PDB:4YIW"
FT HELIX 283..294
FT /evidence="ECO:0007829|PDB:4YIW"
FT STRAND 296..298
FT /evidence="ECO:0007829|PDB:3MPG"
FT HELIX 310..313
FT /evidence="ECO:0007829|PDB:4YIW"
FT TURN 317..319
FT /evidence="ECO:0007829|PDB:4YIW"
FT HELIX 327..329
FT /evidence="ECO:0007829|PDB:4YIW"
FT HELIX 330..337
FT /evidence="ECO:0007829|PDB:4YIW"
FT TURN 338..342
FT /evidence="ECO:0007829|PDB:4YIW"
FT HELIX 346..352
FT /evidence="ECO:0007829|PDB:4YIW"
FT HELIX 355..361
FT /evidence="ECO:0007829|PDB:4YIW"
FT STRAND 376..382
FT /evidence="ECO:0007829|PDB:4YIW"
FT HELIX 389..391
FT /evidence="ECO:0007829|PDB:4YIW"
FT STRAND 393..395
FT /evidence="ECO:0007829|PDB:4YIW"
FT STRAND 409..415
FT /evidence="ECO:0007829|PDB:4YIW"
FT STRAND 418..422
FT /evidence="ECO:0007829|PDB:4YIW"
SQ SEQUENCE 428 AA; 46656 MW; 6AA9493906CCA956 CRC64;
MNYLFKNGRY MNEEGKIVAT DLLVQDGKIA KVAENITADN AEVIDVNGKL IAPGLVDVHV
HLREPGGEHK ETIETGTLAA AKGGFTTICA MPNTRPVPDC REHMEDLQNR IKEKAHVNVL
PYGAITVRQA GSEMTDFETL KELGAFAFTD DGVGVQDASM MLAAMKRAAK LNMAVVAHCE
ENTLINKGCV HEGKFSEKHG LNGIPSVCES VHIARDILLA EAADCHYHVC HVSTKGSVRV
IRDAKRAGIK VTAEVTPHHL VLCEDDIPSA DPNFKMNPPL RGKEDHEALI EGLLDGTIDM
IATDHAPHTA EEKAQGIERA PFGITGFETA FPLLYTNLVK KGIITLEQLI QFLTEKPADT
FGLEAGRLKE GRTADITIID LEQEEEIDPT TFLSKGKNTP FAGWKCQGWP VMTIVGGKIA
WQKESALV
