ID A0A3N6K7E2_9LACT Unreviewed; 535 AA. AC A0A3N6K7E2; DT 13-FEB-2019, integrated into UniProtKB/TrEMBL. DT 13-FEB-2019, sequence version 1. DT 10-APR-2019, entry version 2. 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=D6110_02115 {ECO:0000313|EMBL:RQE07990.1}, EO246_09490 GN {ECO:0000313|EMBL:RWR46039.1}; 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:RQE07990.1, ECO:0000313|Proteomes:UP000268493} RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=IPLA1064 {ECO:0000313|EMBL:RQE07990.1, RC ECO:0000313|Proteomes:UP000268493}; RX PubMed=30455679; DOI=10.3389/fmicb.2018.02654; RA Lopez-Gonzalez M.J., Escobedo S., Rodriguez A., Neves A.R., Janzen T., RA Martinez B.; RT "Adaptive Evolution of Industrial Lactococcus lactis Under Cell RT Envelope Stress Provides Phenotypic Diversity."; RL Front. Microbiol. 9:2654-2654(2018). RN [2] {ECO:0000313|EMBL:RQE07990.1} RP NUCLEOTIDE SEQUENCE. RC STRAIN=IPLA1064 {ECO:0000313|EMBL:RQE07990.1}; RA Lopez-Gonzales M.J., Escobedo S., Rodriguez A., Neves A.R., Janzen T., RA Martinez B.; RL Submitted (SEP-2018) to the EMBL/GenBank/DDBJ databases. RN [3] {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. 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|HAMAP-Rule:MF_01227, CC ECO:0000256|SAAS:SAAS01116648}; CC -!- ACTIVITY REGULATION: Allosterically activated by GTP, when CC glutamine is the substrate; GTP has no effect on the reaction when CC ammonia is the substrate. The allosteric effector GTP functions by CC stabilizing the protein conformation that binds the tetrahedral CC intermediate(s) formed during glutamine hydrolysis. Inhibited by CC the product CTP, via allosteric rather than competitive CC inhibition. {ECO:0000256|HAMAP-Rule:MF_01227}. CC -!- PATHWAY: Pyrimidine metabolism; CTP biosynthesis via de novo CC pathway; CTP from UDP: step 2/2. {ECO:0000256|HAMAP-Rule:MF_01227, CC ECO:0000256|SAAS:SAAS00710815}. CC -!- SUBUNIT: Homotetramer. {ECO:0000256|HAMAP-Rule:MF_01227, CC ECO:0000256|SAAS:SAAS00710816}. CC -!- MISCELLANEOUS: CTPSs have evolved a hybrid strategy for CC distinguishing between UTP and CTP. The overlapping regions of the CC product feedback inhibitory and substrate sites recognize a common CC feature in both compounds, the triphosphate moiety. To CC differentiate isosteric substrate and product pyrimidine rings, an CC additional pocket far from the expected kinase/ligase catalytic CC site, specifically recognizes the cytosine and ribose portions of CC the product inhibitor. {ECO:0000256|HAMAP-Rule:MF_01227}. CC -!- SIMILARITY: Belongs to the CTP synthase family. CC {ECO:0000256|HAMAP-Rule:MF_01227, ECO:0000256|SAAS:SAAS00710794}. CC -!- CAUTION: Lacks conserved residue(s) required for the propagation CC of feature annotation. {ECO:0000256|HAMAP-Rule:MF_01227}. CC -!- CAUTION: The sequence shown here is derived from an CC EMBL/GenBank/DDBJ whole genome shotgun (WGS) entry which is CC preliminary data. {ECO:0000313|EMBL:RWR46039.1}. 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; RAGG01000003; RQE07990.1; -; Genomic_DNA. DR EMBL; SAXH01000014; RWR46039.1; -; Genomic_DNA. DR UniPathway; UPA00159; UER00277. DR Proteomes; UP000268493; Unassembled WGS sequence. DR Proteomes; UP000285859; Unassembled WGS sequence. DR CDD; cd01746; GATase1_CTP_Synthase; 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 {ECO:0000256|HAMAP-Rule:MF_01227, KW ECO:0000256|SAAS:SAAS00710699}; KW Complete proteome {ECO:0000313|Proteomes:UP000268493, KW ECO:0000313|Proteomes:UP000285859}; KW Glutamine amidotransferase {ECO:0000256|HAMAP-Rule:MF_01227, KW ECO:0000256|PROSITE-ProRule:PRU00605, ECO:0000256|SAAS:SAAS00710676}; KW Ligase {ECO:0000256|HAMAP-Rule:MF_01227, KW ECO:0000256|SAAS:SAAS00710762, ECO:0000313|EMBL:RWR46039.1}; KW Magnesium {ECO:0000256|HAMAP-Rule:MF_01227, KW ECO:0000256|SAAS:SAAS00710689}; KW Metal-binding {ECO:0000256|HAMAP-Rule:MF_01227, KW ECO:0000256|SAAS:SAAS00710675}; KW Nucleotide-binding {ECO:0000256|HAMAP-Rule:MF_01227, KW ECO:0000256|SAAS:SAAS00710810}; KW Pyrimidine biosynthesis {ECO:0000256|HAMAP-Rule:MF_01227, KW ECO:0000256|SAAS:SAAS00710748}. FT DOMAIN 293 535 Glutamine amidotransferase type-1. FT {ECO:0000259|PROSITE:PS51273}. FT NP_BIND 15 20 ATP. {ECO:0000256|HAMAP-Rule:MF_01227}. FT NP_BIND 149 151 Allosteric inhibitor CTP. FT {ECO:0000256|HAMAP-Rule:MF_01227}. FT NP_BIND 189 194 Allosteric inhibitor CTP; alternate. FT {ECO:0000256|HAMAP-Rule:MF_01227}. FT NP_BIND 189 194 UTP; alternate. {ECO:0000256|HAMAP-Rule: FT MF_01227}. FT REGION 1 268 Amidoligase domain. {ECO:0000256|HAMAP- FT Rule:MF_01227}. FT REGION 383 386 L-glutamine binding. {ECO:0000256|HAMAP- FT Rule:MF_01227}. FT ACT_SITE 382 382 Nucleophile. {ECO:0000256|PROSITE- FT ProRule:PRU00605}. FT ACT_SITE 382 382 Nucleophile; for glutamine hydrolysis. FT {ECO:0000256|HAMAP-Rule:MF_01227}. FT ACT_SITE 509 509 {ECO:0000256|HAMAP-Rule:MF_01227, FT ECO:0000256|PROSITE-ProRule:PRU00605}. FT ACT_SITE 511 511 {ECO:0000256|HAMAP-Rule:MF_01227, FT ECO:0000256|PROSITE-ProRule:PRU00605}. FT METAL 72 72 Magnesium. {ECO:0000256|HAMAP-Rule: FT MF_01227}. FT METAL 142 142 Magnesium. {ECO:0000256|HAMAP-Rule: FT MF_01227}. FT BINDING 14 14 Allosteric inhibitor CTP; alternate. FT {ECO:0000256|HAMAP-Rule:MF_01227}. FT BINDING 14 14 UTP; alternate. {ECO:0000256|HAMAP-Rule: FT MF_01227}. FT BINDING 55 55 L-glutamine. {ECO:0000256|HAMAP-Rule: FT MF_01227}. FT BINDING 72 72 ATP. {ECO:0000256|HAMAP-Rule:MF_01227}. FT BINDING 225 225 Allosteric inhibitor CTP; alternate. FT {ECO:0000256|HAMAP-Rule:MF_01227}. FT BINDING 225 225 UTP; alternate. {ECO:0000256|HAMAP-Rule: FT MF_01227}. FT BINDING 243 243 ATP. {ECO:0000256|HAMAP-Rule:MF_01227}. FT BINDING 355 355 L-glutamine; via carbonyl oxygen. FT {ECO:0000256|HAMAP-Rule:MF_01227}. FT BINDING 406 406 L-glutamine. {ECO:0000256|HAMAP-Rule: FT MF_01227}. FT BINDING 464 464 L-glutamine; via amide nitrogen. FT {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 //