ID PYRG_GEOLS Reviewed; 535 AA. AC B3EAK5; DT 14-APR-2009, integrated into UniProtKB/Swiss-Prot. DT 22-JUL-2008, sequence version 1. DT 29-SEP-2021, entry version 79. DE RecName: Full=CTP synthase {ECO:0000255|HAMAP-Rule:MF_01227}; DE EC=6.3.4.2 {ECO:0000255|HAMAP-Rule:MF_01227}; DE AltName: Full=Cytidine 5'-triphosphate synthase {ECO:0000255|HAMAP-Rule:MF_01227}; DE AltName: Full=Cytidine triphosphate synthetase {ECO:0000255|HAMAP-Rule:MF_01227}; DE Short=CTP synthetase {ECO:0000255|HAMAP-Rule:MF_01227}; DE Short=CTPS {ECO:0000255|HAMAP-Rule:MF_01227}; DE AltName: Full=UTP--ammonia ligase {ECO:0000255|HAMAP-Rule:MF_01227}; GN Name=pyrG {ECO:0000255|HAMAP-Rule:MF_01227}; OrderedLocusNames=Glov_1727; OS Geobacter lovleyi (strain ATCC BAA-1151 / DSM 17278 / SZ). OC Bacteria; Proteobacteria; Deltaproteobacteria; Desulfuromonadales; OC Geobacteraceae; Geobacter. OX NCBI_TaxID=398767; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=ATCC BAA-1151 / DSM 17278 / SZ; RG US DOE Joint Genome Institute; RA Lucas S., Copeland A., Lapidus A., Glavina del Rio T., Dalin E., Tice H., RA Bruce D., Goodwin L., Pitluck S., Chertkov O., Meincke L., Brettin T., RA Detter J.C., Han C., Tapia R., Kuske C.R., Schmutz J., Larimer F., Land M., RA Hauser L., Kyrpides N., Mikhailova N., Sung Y., Fletcher K.E., RA Ritalahti K.M., Loeffler F.E., Richardson P.; RT "Complete sequence of chromosome of Geobacter lovleyi SZ."; RL Submitted (MAY-2008) to the EMBL/GenBank/DDBJ databases. CC -!- FUNCTION: Catalyzes the ATP-dependent amination of UTP to CTP with CC either L-glutamine or ammonia as the source of nitrogen. Regulates CC intracellular CTP levels through interactions with the four CC ribonucleotide triphosphates. {ECO:0000255|HAMAP-Rule:MF_01227}. CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + H2O + L-glutamine + UTP = ADP + CTP + 2 H(+) + L- CC glutamate + phosphate; Xref=Rhea:RHEA:26426, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:29985, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:37563, ChEBI:CHEBI:43474, ChEBI:CHEBI:46398, CC ChEBI:CHEBI:58359, ChEBI:CHEBI:456216; EC=6.3.4.2; CC Evidence={ECO:0000255|HAMAP-Rule:MF_01227}; CC -!- ACTIVITY REGULATION: Allosterically activated by GTP, when glutamine is CC the substrate; GTP has no effect on the reaction when ammonia is the CC substrate. The allosteric effector GTP functions by stabilizing the CC protein conformation that binds the tetrahedral intermediate(s) formed CC during glutamine hydrolysis. Inhibited by the product CTP, via CC allosteric rather than competitive inhibition. {ECO:0000255|HAMAP- CC Rule:MF_01227}. CC -!- PATHWAY: Pyrimidine metabolism; CTP biosynthesis via de novo pathway; CC CTP from UDP: step 2/2. {ECO:0000255|HAMAP-Rule:MF_01227}. CC -!- SUBUNIT: Homotetramer. {ECO:0000255|HAMAP-Rule:MF_01227}. CC -!- MISCELLANEOUS: CTPSs have evolved a hybrid strategy for distinguishing CC between UTP and CTP. The overlapping regions of the product feedback CC inhibitory and substrate sites recognize a common feature in both CC compounds, the triphosphate moiety. To differentiate isosteric CC substrate and product pyrimidine rings, an additional pocket far from CC the expected kinase/ligase catalytic site, specifically recognizes the CC cytosine and ribose portions of the product inhibitor. CC {ECO:0000255|HAMAP-Rule:MF_01227}. CC -!- SIMILARITY: Belongs to the CTP synthase family. {ECO:0000255|HAMAP- CC Rule:MF_01227}. 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; CP001089; ACD95443.1; -; Genomic_DNA. DR RefSeq; WP_012469783.1; NC_010814.1. DR SMR; B3EAK5; -. DR STRING; 398767.Glov_1727; -. DR EnsemblBacteria; ACD95443; ACD95443; Glov_1727. DR KEGG; glo:Glov_1727; -. DR eggNOG; COG0504; Bacteria. DR HOGENOM; CLU_011675_5_0_7; -. DR OMA; EFNNAYR; -. DR OrthoDB; 783657at2; -. DR BioCyc; GLOV398767:G1GC4-1729-MONOMER; -. DR UniPathway; UPA00159; UER00277. DR Proteomes; UP000002420; Chromosome. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0003883; F:CTP synthase activity; IEA:UniProtKB-UniRule. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0044210; P:'de novo' CTP biosynthetic process; IEA:UniProtKB-UniPathway. DR GO; GO:0006541; P:glutamine metabolic process; IEA:UniProtKB-KW. DR CDD; cd03113; CTPS_N; 1. DR CDD; cd01746; GATase1_CTP_Synthase; 1. DR Gene3D; 3.40.50.300; -; 1. DR Gene3D; 3.40.50.880; -; 1. DR HAMAP; MF_01227; PyrG; 1. DR InterPro; IPR029062; Class_I_gatase-like. DR InterPro; IPR004468; CTP_synthase. DR InterPro; IPR017456; CTP_synthase_N. DR InterPro; IPR017926; GATASE. DR InterPro; IPR033828; GATase1_CTP_Synthase. DR InterPro; IPR027417; P-loop_NTPase. DR PANTHER; PTHR11550; PTHR11550; 1. DR Pfam; PF06418; CTP_synth_N; 1. DR Pfam; PF00117; GATase; 1. DR SUPFAM; SSF52317; SSF52317; 1. DR SUPFAM; SSF52540; SSF52540; 1. DR TIGRFAMs; TIGR00337; PyrG; 1. DR PROSITE; PS51273; GATASE_TYPE_1; 1. PE 3: Inferred from homology; KW ATP-binding; Glutamine amidotransferase; Ligase; Magnesium; Metal-binding; KW Nucleotide-binding; Pyrimidine biosynthesis; Reference proteome. FT CHAIN 1..535 FT /note="CTP synthase" FT /id="PRO_1000139463" FT DOMAIN 292..534 FT /note="Glutamine amidotransferase type-1" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227" FT NP_BIND 15..20 FT /note="ATP" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227" FT NP_BIND 147..149 FT /note="CTP; allosteric inhibitor" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227" FT NP_BIND 187..192 FT /note="CTP; allosteric inhibitor; alternate" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227" FT NP_BIND 187..192 FT /note="UTP; alternate" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227" FT REGION 1..266 FT /note="Amidoligase domain" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227" FT REGION 382..385 FT /note="L-glutamine binding" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227" FT ACT_SITE 381 FT /note="Nucleophile; for glutamine hydrolysis" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227" FT ACT_SITE 507 FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227" FT ACT_SITE 509 FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227" FT METAL 72 FT /note="Magnesium" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227" FT METAL 140 FT /note="Magnesium" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227" FT BINDING 14 FT /note="CTP; allosteric inhibitor; alternate" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227" FT BINDING 14 FT /note="UTP; alternate" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227" FT BINDING 72 FT /note="ATP" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227" FT BINDING 223 FT /note="CTP; allosteric inhibitor; alternate" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227" FT BINDING 223 FT /note="UTP; alternate" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227" FT BINDING 354 FT /note="L-glutamine; via carbonyl oxygen" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227" FT BINDING 405 FT /note="L-glutamine" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227" FT BINDING 462 FT /note="L-glutamine; via amide nitrogen" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227" SQ SEQUENCE 535 AA; 59767 MW; B86BADC1F55A3205 CRC64; MKTKFIFITG GVVSSIGKGL AAASLGALLE SRGLRVTMQK LDPYINVDPG TMSPFQHGEV FVTDDGAETD LDLGHYERYT SARLSKKSNF TTGQVYFSVI DKERRGDYLG GTVQVIPHIT DEIKSKIIEN AKGADVAIVE VGGTVGDIES LPFLEAIRQF RFDRGAGNTL YVHVTLVPYI RTAGEMKTKP TQHSVMELRK IGIQPDILLC RCDRELPQDM KKKISLFCNV EESCVIPSVD SEHIYAVPLA LNKERLDEQV VEKLNIWTKQ PDLTPWQDVV ETLRHPSHGE VRIAIVGKYV NLTESYKSLA EALTHGGIAN DCRVYLKYVD AEKIEENGVE GWLDDVDGVL VPGGFGERGT EGKVLAIEYA RTRQIPFFGI CLGMQMAAIE FARNVCGLAK ACSTEFKNDC KEPVIHLMEE QKSVNKKGGT MRLGACPCTV TKGTKAFDAY NEADISERHR HRYEFNNTYR ELMTTKGLVL SGINQQKDLV EIIELPDHPW FLACQFHPEF KSKPLVPHPL FRAFIGASLT HRNQR //