ID A0A3N6K7E2_9LACT Unreviewed; 535 AA. AC A0A3N6K7E2; DT 13-FEB-2019, integrated into UniProtKB/TrEMBL. DT 13-FEB-2019, sequence version 1. DT 22-FEB-2023, entry version 17. DE RecName: Full=CTP synthase {ECO:0000256|HAMAP-Rule:MF_01227}; DE EC=6.3.4.2 {ECO:0000256|HAMAP-Rule:MF_01227}; DE AltName: Full=Cytidine 5'-triphosphate synthase {ECO:0000256|HAMAP-Rule:MF_01227}; DE AltName: Full=Cytidine triphosphate synthetase {ECO:0000256|HAMAP-Rule:MF_01227}; DE Short=CTP synthetase {ECO:0000256|HAMAP-Rule:MF_01227}; DE Short=CTPS {ECO:0000256|HAMAP-Rule:MF_01227}; DE AltName: Full=UTP--ammonia ligase {ECO:0000256|HAMAP-Rule:MF_01227}; GN Name=pyrG {ECO:0000256|HAMAP-Rule:MF_01227}; GN ORFNames=EO246_09490 {ECO:0000313|EMBL:RWR46039.1}, EQZ99_07660 GN {ECO:0000313|EMBL:QBC37866.1}, GJ670_06685 GN {ECO:0000313|EMBL:NLS47118.1}, GTP08_11215 GN {ECO:0000313|EMBL:NEX56218.1}, I6G22_08775 GN {ECO:0000313|EMBL:QPT50751.1}; OS Lactococcus lactis. OC Bacteria; Firmicutes; Bacilli; Lactobacillales; Streptococcaceae; OC Lactococcus. OX NCBI_TaxID=1358 {ECO:0000313|EMBL:RWR46039.1, ECO:0000313|Proteomes:UP000285859}; RN [1] {ECO:0000313|EMBL:QBC37866.1, ECO:0000313|Proteomes:UP000290947} RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=SRCM103457 {ECO:0000313|EMBL:QBC37866.1, RC ECO:0000313|Proteomes:UP000290947}; RA Cho K.H., Jeong S.-Y., Jeong D.-Y.; RT "Genome sequence of Lactococcus lactis SRCM103457."; RL Submitted (JAN-2019) to the EMBL/GenBank/DDBJ databases. RN [2] {ECO:0000313|EMBL:RWR46039.1, ECO:0000313|Proteomes:UP000285859} RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=C2D {ECO:0000313|EMBL:RWR46039.1, RC ECO:0000313|Proteomes:UP000285859}; RA Sundararaman A., Tamang J.-P., Halami P.; RT "Whole genome sequence of Lactococcus lactis isolated from cow milk."; RL Submitted (JAN-2019) to the EMBL/GenBank/DDBJ databases. RN [3] {ECO:0000313|EMBL:NLS47118.1} RP NUCLEOTIDE SEQUENCE. RC STRAIN=D53 {ECO:0000313|EMBL:NLS47118.1}; RA Callon C., Fretin M., Theil S., Rifa E., Laforce P., Fernandez B.; RT "Draft Genome Sequences of Three bacterial strains that inhibit the growth RT of Shiga-toxin producing Escherichia coli (STEC) in raw milk cheese."; RL Submitted (NOV-2019) to the EMBL/GenBank/DDBJ databases. RN [4] {ECO:0000313|EMBL:NEX56218.1, ECO:0000313|Proteomes:UP000477402} RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=MS22336 {ECO:0000313|EMBL:NEX56218.1, RC ECO:0000313|Proteomes:UP000477402}; RA Bragason E., Hansen E.B., Guya M.E., Berhe T.; RT "Draft Genome Sequences of L. lactis strains MS22333, MS22334, MS22336, and RT MS22337, Isolated from Spontaneous Fermented Camel Milk in Ethiopia."; RL Submitted (DEC-2019) to the EMBL/GenBank/DDBJ databases. RN [5] {ECO:0000313|EMBL:QPT50751.1, ECO:0000313|Proteomes:UP000594798} RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=FDAARGOS_865 {ECO:0000313|EMBL:QPT50751.1, RC ECO:0000313|Proteomes:UP000594798}; RA Sproer C., Gronow S., Severitt S., Schroder I., Tallon L., Sadzewicz L., RA Zhao X., Boylan J., Ott S., Bowen H., Vavikolanu K., Mehta A., RA Aluvathingal J., Nadendla S., Lowell S., Myers T., Yan Y., Sichtig H.; RT "FDA dAtabase for Regulatory Grade micrObial Sequences (FDA-ARGOS): RT Supporting development and validation of Infectious Disease Dx tests."; RL Submitted (DEC-2020) 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:0000256|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:0000256|ARBA:ARBA00000314, ECO:0000256|HAMAP- CC Rule:MF_01227}; CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + NH4(+) + UTP = ADP + CTP + 2 H(+) + phosphate; CC Xref=Rhea:RHEA:16597, ChEBI:CHEBI:15378, ChEBI:CHEBI:28938, CC ChEBI:CHEBI:30616, ChEBI:CHEBI:37563, ChEBI:CHEBI:43474, CC ChEBI:CHEBI:46398, ChEBI:CHEBI:456216; Evidence={ECO:0000256|HAMAP- CC Rule:MF_01227}; CC -!- CATALYTIC ACTIVITY: CC Reaction=H2O + L-glutamine = L-glutamate + NH4(+); CC Xref=Rhea:RHEA:15889, ChEBI:CHEBI:15377, ChEBI:CHEBI:28938, CC ChEBI:CHEBI:29985, ChEBI:CHEBI:58359; Evidence={ECO:0000256|HAMAP- CC 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:0000256|HAMAP- CC Rule:MF_01227}. CC -!- PATHWAY: Pyrimidine metabolism; CTP biosynthesis via de novo pathway; CC CTP from UDP: step 2/2. {ECO:0000256|ARBA:ARBA00005171, CC ECO:0000256|HAMAP-Rule:MF_01227}. CC -!- SUBUNIT: Homotetramer. {ECO:0000256|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:0000256|HAMAP-Rule:MF_01227}. CC -!- SIMILARITY: Belongs to the CTP synthase family. CC {ECO:0000256|ARBA:ARBA00007533, ECO:0000256|HAMAP-Rule:MF_01227}. CC -!- CAUTION: Lacks conserved residue(s) required for the propagation of CC feature annotation. {ECO:0000256|HAMAP-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; WWDJ01000115; NEX56218.1; -; Genomic_DNA. DR EMBL; WKFC01000002; NLS47118.1; -; Genomic_DNA. DR EMBL; CP035757; QBC37866.1; -; Genomic_DNA. DR EMBL; CP065737; QPT50751.1; -; Genomic_DNA. DR EMBL; SAXH01000014; RWR46039.1; -; Genomic_DNA. DR RefSeq; WP_015425877.1; NZ_WWDJ01000115.1. DR AlphaFoldDB; A0A3N6K7E2; -. DR EnsemblBacteria; QBC37866; QBC37866; EQZ99_07660. DR GeneID; 69712487; -. DR UniPathway; UPA00159; UER00277. DR Proteomes; UP000285859; Unassembled WGS sequence. DR Proteomes; UP000290947; Chromosome. DR Proteomes; UP000477402; Unassembled WGS sequence. DR Proteomes; UP000594798; Chromosome. DR Proteomes; UP000657979; Unassembled WGS sequence. 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; 3.40.50.880; -; 1. DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 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; CTP SYNTHASE; 1. DR PANTHER; PTHR11550:SF0; CTP SYNTHASE-RELATED; 1. DR Pfam; PF06418; CTP_synth_N; 1. DR Pfam; PF00117; GATase; 1. DR SUPFAM; SSF52317; Class I glutamine amidotransferase-like; 1. DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1. DR TIGRFAMs; TIGR00337; PyrG; 1. DR PROSITE; PS51273; GATASE_TYPE_1; 1. PE 3: Inferred from homology; KW ATP-binding {ECO:0000256|ARBA:ARBA00022840, ECO:0000256|HAMAP- KW Rule:MF_01227}; KW Glutamine amidotransferase {ECO:0000256|ARBA:ARBA00022962, KW ECO:0000256|HAMAP-Rule:MF_01227}; KW Ligase {ECO:0000256|ARBA:ARBA00022598, ECO:0000256|HAMAP-Rule:MF_01227}; KW Magnesium {ECO:0000256|HAMAP-Rule:MF_01227}; KW Metal-binding {ECO:0000256|HAMAP-Rule:MF_01227}; KW Nucleotide-binding {ECO:0000256|ARBA:ARBA00022741, ECO:0000256|HAMAP- KW Rule:MF_01227}; KW Pyrimidine biosynthesis {ECO:0000256|ARBA:ARBA00022975, ECO:0000256|HAMAP- KW Rule:MF_01227}. FT DOMAIN 4..268 FT /note="CTP synthase N-terminal" FT /evidence="ECO:0000259|Pfam:PF06418" FT DOMAIN 303..528 FT /note="Glutamine amidotransferase" FT /evidence="ECO:0000259|Pfam:PF00117" FT REGION 1..268 FT /note="Amidoligase domain" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT ACT_SITE 382 FT /note="Nucleophile" FT /evidence="ECO:0000256|PROSITE-ProRule:PRU00605" FT ACT_SITE 382 FT /note="Nucleophile; for glutamine hydrolysis" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT ACT_SITE 509 FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227, FT ECO:0000256|PROSITE-ProRule:PRU00605" FT ACT_SITE 511 FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227, FT ECO:0000256|PROSITE-ProRule:PRU00605" FT BINDING 14 FT /ligand="CTP" FT /ligand_id="ChEBI:CHEBI:37563" FT /ligand_note="allosteric inhibitor" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT BINDING 14 FT /ligand="UTP" FT /ligand_id="ChEBI:CHEBI:46398" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT BINDING 15..20 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT BINDING 55 FT /ligand="L-glutamine" FT /ligand_id="ChEBI:CHEBI:58359" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT BINDING 72 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT BINDING 72 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT BINDING 142 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT BINDING 149..151 FT /ligand="CTP" FT /ligand_id="ChEBI:CHEBI:37563" FT /ligand_note="allosteric inhibitor" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT BINDING 189..194 FT /ligand="CTP" FT /ligand_id="ChEBI:CHEBI:37563" FT /ligand_note="allosteric inhibitor" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT BINDING 189..194 FT /ligand="UTP" FT /ligand_id="ChEBI:CHEBI:46398" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT BINDING 225 FT /ligand="CTP" FT /ligand_id="ChEBI:CHEBI:37563" FT /ligand_note="allosteric inhibitor" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT BINDING 225 FT /ligand="UTP" FT /ligand_id="ChEBI:CHEBI:46398" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT BINDING 243 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT BINDING 355 FT /ligand="L-glutamine" FT /ligand_id="ChEBI:CHEBI:58359" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT BINDING 383..386 FT /ligand="L-glutamine" FT /ligand_id="ChEBI:CHEBI:58359" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT BINDING 406 FT /ligand="L-glutamine" FT /ligand_id="ChEBI:CHEBI:58359" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT BINDING 464 FT /ligand="L-glutamine" FT /ligand_id="ChEBI:CHEBI:58359" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" SQ SEQUENCE 535 AA; 59538 MW; 95CD50B89CF409ED CRC64; MSTKYIFVTG GGTSSMGKGI VAASLGRLLK NRGLKVTVQK FDPYLNIDPG TMSPYQHGEV FVTDDGAETD LDLGHYERFI DINLNKYSNV TSGKVYSEIL RKERKGEYLG ATVQMVPHVT NMLKEKIKRA ATTTDADIII TEVGGTVGDM ESLPFIEALR QMKAEVGADN VMYIHTVPIL HLRAAGELKT KIAQNATKTL REYGIQANML VLRSEVPITT EMRDKIAMFC DVAPEAVIQS LDVEHLYQIP LNLQAQNMDQ IVCDHLKLDA PKADMTEWSA MVDHVMNLKK KVKIALVGKY VELPDAYISV TEALKHAGYS SDAEVDINWV NANDVTDENV ADLVGDAAGI IVPGGFGHRG TEGKIAAIKY ARENDVPMLG ICLGMQLTAV EFARNVLGLE GAHSFELDPE TKYPVIDIMR DQVDVEDMGG TLRLGLYPAK LKNGSRAKAA YNDAEVVQRR HRHRYEFNNK FREDFEKAGF VFSGVSPDNR LVEIVELSDK KFFVACQYHP ELQSRPNRPE ELYTEFIRVA VENSK //