ID PYRC_KLEP7 Reviewed; 348 AA. AC A6T7D6; DT 15-JAN-2008, integrated into UniProtKB/Swiss-Prot. DT 21-AUG-2007, sequence version 1. DT 10-OCT-2018, entry version 64. DE RecName: Full=Dihydroorotase {ECO:0000255|HAMAP-Rule:MF_00219}; DE Short=DHOase {ECO:0000255|HAMAP-Rule:MF_00219}; DE EC=3.5.2.3 {ECO:0000255|HAMAP-Rule:MF_00219, ECO:0000269|PubMed:20676924}; GN Name=pyrC {ECO:0000255|HAMAP-Rule:MF_00219}; GN OrderedLocusNames=KPN78578_10460; ORFNames=KPN_01074; OS Klebsiella pneumoniae subsp. pneumoniae (strain ATCC 700721 / MGH OS 78578). OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales; OC Enterobacteriaceae; Klebsiella. OX NCBI_TaxID=272620; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=ATCC 700721 / MGH 78578; RG The Klebsiella pneumonia Genome Sequencing Project; RA McClelland M., Sanderson E.K., Spieth J., Clifton W.S., Latreille P., RA Sabo A., Pepin K., Bhonagiri V., Porwollik S., Ali J., Wilson R.K.; RL Submitted (SEP-2006) to the EMBL/GenBank/DDBJ databases. RN [2] RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES, RP SUBUNIT, AND MUTAGENESIS OF HIS-17; HIS-19; LYS-103; HIS-140; HIS-178 RP AND ASP-251. RC STRAIN=ATCC 13883 / DSM 30104 / JCM 1662 / NBRC 14940 / NCIMB 13281 / RC NCTC 9633; RX PubMed=20676924; DOI=10.1007/s10930-010-9272-2; RA Wang C.C., Tsau H.W., Chen W.T., Huang C.Y.; RT "Identification and characterization of a putative dihydroorotase, RT KPN01074, from Klebsiella pneumoniae."; RL Protein J. 29:445-452(2010). CC -!- FUNCTION: Catalyzes the reversible cyclization of carbamoyl CC aspartate to dihydroorotate. {ECO:0000255|HAMAP-Rule:MF_00219, CC ECO:0000269|PubMed:20676924}. CC -!- CATALYTIC ACTIVITY: (S)-dihydroorotate + H(2)O = N-carbamoyl-L- CC aspartate. {ECO:0000255|HAMAP-Rule:MF_00219, CC ECO:0000269|PubMed:20676924}. CC -!- COFACTOR: CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; CC Evidence={ECO:0000255|HAMAP-Rule:MF_00219}; CC Name=Co(2+); Xref=ChEBI:CHEBI:48828; CC Evidence={ECO:0000269|PubMed:20676924}; CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC Evidence={ECO:0000269|PubMed:20676924}; CC Name=Ni(2+); Xref=ChEBI:CHEBI:49786; CC Evidence={ECO:0000269|PubMed:20676924}; CC Note=Binds 2 Zn(2+) ions per subunit (By similarity). In vitro, CC shows higher activity with Co(2+), Mg(2+), Ni(2+) and Mn(2+) than CC with Zn(2+) (PubMed:20676924). {ECO:0000255|HAMAP-Rule:MF_00219, CC ECO:0000269|PubMed:20676924}; CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=0.04 mM for dihydroorotate {ECO:0000269|PubMed:20676924}; CC Vmax=8.87 umol/min/mg enzyme {ECO:0000269|PubMed:20676924}; CC pH dependence: CC Optimum pH is 9.0. {ECO:0000269|PubMed:20676924}; CC Temperature dependence: CC Optimum temperature is around 60 degrees Celsius. CC {ECO:0000269|PubMed:20676924}; CC -!- PATHWAY: Pyrimidine metabolism; UMP biosynthesis via de novo CC pathway; (S)-dihydroorotate from bicarbonate: step 3/3. CC {ECO:0000255|HAMAP-Rule:MF_00219}. CC -!- SUBUNIT: Homodimer. {ECO:0000255|HAMAP-Rule:MF_00219, CC ECO:0000269|PubMed:20676924}. CC -!- SIMILARITY: Belongs to the metallo-dependent hydrolases CC superfamily. DHOase family. Class II DHOase subfamily. CC {ECO:0000255|HAMAP-Rule:MF_00219, ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; CP000647; ABR76507.1; -; Genomic_DNA. DR RefSeq; WP_004176586.1; NC_009648.1. DR ProteinModelPortal; A6T7D6; -. DR SMR; A6T7D6; -. DR STRING; 272620.KPN_01074; -. DR PRIDE; A6T7D6; -. DR EnsemblBacteria; ABR76507; ABR76507; KPN_01074. DR KEGG; kpn:KPN_01074; -. DR eggNOG; ENOG4105EKE; Bacteria. DR eggNOG; COG0418; LUCA. DR HOGENOM; HOG000256259; -. DR KO; K01465; -. DR OMA; HLRDGAM; -. DR BRENDA; 3.5.2.3; 2814. DR UniPathway; UPA00070; UER00117. DR Proteomes; UP000000265; 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 GO; GO:0019856; P:pyrimidine nucleobase biosynthetic process; IEA:InterPro. DR CDD; cd01294; DHOase; 1. DR HAMAP; MF_00219; PyrC_classII; 1. DR InterPro; IPR006680; Amidohydro-rel. DR InterPro; IPR004721; DHOdimr. DR InterPro; IPR002195; Dihydroorotase_CS. DR InterPro; IPR032466; Metal_Hydrolase. DR PANTHER; PTHR43137; PTHR43137; 1. DR Pfam; PF01979; Amidohydro_1; 1. DR PIRSF; PIRSF001237; DHOdimr; 1. DR SUPFAM; SSF51556; SSF51556; 1. DR TIGRFAMs; TIGR00856; pyrC_dimer; 1. DR PROSITE; PS00483; DIHYDROOROTASE_2; 1. PE 1: Evidence at protein level; KW Complete proteome; Hydrolase; Metal-binding; Pyrimidine biosynthesis; KW Reference proteome; Zinc. FT CHAIN 1 348 Dihydroorotase. FT /FTId=PRO_1000024020. FT REGION 19 21 Substrate binding. {ECO:0000255|HAMAP- FT Rule:MF_00219}. FT ACT_SITE 251 251 {ECO:0000255|HAMAP-Rule:MF_00219}. FT METAL 17 17 Zinc 1; via tele nitrogen. FT {ECO:0000255|HAMAP-Rule:MF_00219}. FT METAL 19 19 Zinc 1; via tele nitrogen. FT {ECO:0000255|HAMAP-Rule:MF_00219}. FT METAL 103 103 Zinc 1; via carbamate group. FT {ECO:0000255|HAMAP-Rule:MF_00219}. FT METAL 103 103 Zinc 2; via carbamate group. FT {ECO:0000255|HAMAP-Rule:MF_00219}. FT METAL 140 140 Zinc 2; via pros nitrogen. FT {ECO:0000255|HAMAP-Rule:MF_00219}. FT METAL 178 178 Zinc 2; via tele nitrogen. FT {ECO:0000255|HAMAP-Rule:MF_00219}. FT METAL 251 251 Zinc 1. {ECO:0000255|HAMAP- FT Rule:MF_00219}. FT BINDING 45 45 Substrate. {ECO:0000255|HAMAP- FT Rule:MF_00219}. FT BINDING 140 140 Substrate. {ECO:0000255|HAMAP- FT Rule:MF_00219}. FT BINDING 223 223 Substrate; via amide nitrogen and FT carbonyl oxygen. {ECO:0000255|HAMAP- FT Rule:MF_00219}. FT BINDING 255 255 Substrate. {ECO:0000255|HAMAP- FT Rule:MF_00219}. FT BINDING 267 267 Substrate; via carbonyl oxygen. FT {ECO:0000255|HAMAP-Rule:MF_00219}. FT MOD_RES 103 103 N6-carboxylysine. {ECO:0000255|HAMAP- FT Rule:MF_00219}. FT MUTAGEN 17 17 H->A: Lack of activity. FT {ECO:0000269|PubMed:20676924}. FT MUTAGEN 19 19 H->A: Lack of activity. FT {ECO:0000269|PubMed:20676924}. FT MUTAGEN 103 103 K->A: Lack of activity. FT {ECO:0000269|PubMed:20676924}. FT MUTAGEN 140 140 H->A: Lack of activity. FT {ECO:0000269|PubMed:20676924}. FT MUTAGEN 178 178 H->A: Lack of activity. FT {ECO:0000269|PubMed:20676924}. FT MUTAGEN 251 251 D->A: Lack of activity. FT {ECO:0000269|PubMed:20676924}. FT MUTAGEN 251 251 D->E: 4-fold increase in activity. FT {ECO:0000269|PubMed:20676924}. SQ SEQUENCE 348 AA; 38821 MW; 2B841BB50B30506D CRC64; MTAQSQVLKI RRPDDWHIHL RDDDMLKTVV PYTSEFYGRA IVMPNLVPPV TTVAAAIAYR QRIMDAVPAG HDFTPLMTCY LTDSLDPAEL ERGFNEGVFT AAKLYPANAT TNSSHGVTST DAIMPVLERM EKLGMPLLVH GEVTHAEIDI FDREARFIET VMEPLRQRLP GLKVVFEHIT TKDAAEYVRD GNELLAATIT PQHLMFNRNH MLVGGIRPHL YCLPVLKRNI HQQALRELVA SGFSRAFLGT DSAPHARHRK EASCGCAGCF NAPTALGSYA TVFEEMNALQ HFEAFCSLNG PRFYGLPVNE SYVELVREET TVVDSIALPN DTLVPFLAGE TVRWTVKK //