ID A0A2R3JQD7_9LACO Unreviewed; 536 AA. AC A0A2R3JQD7; DT 20-JUN-2018, integrated into UniProtKB/TrEMBL. DT 20-JUN-2018, sequence version 1. DT 16-JAN-2019, entry version 5. 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=C5Z25_08525 {ECO:0000313|EMBL:AVK61821.1}; OS Lactobacillus sp. CBA3605. OC Bacteria; Firmicutes; Bacilli; Lactobacillales; Lactobacillaceae; OC Lactobacillus. OX NCBI_TaxID=2099788 {ECO:0000313|EMBL:AVK61821.1, ECO:0000313|Proteomes:UP000239036}; RN [1] {ECO:0000313|EMBL:AVK61821.1, ECO:0000313|Proteomes:UP000239036} RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=CBA3605 {ECO:0000313|EMBL:AVK61821.1, RC ECO:0000313|Proteomes:UP000239036}; RA Jung M.Y.; RT "Complete genome sequence of Lactobacillus sp. CBA3605."; RL Submitted (FEB-2018) 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 --------------------------------------------------------------------------- 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; CP027190; AVK61821.1; -; Genomic_DNA. DR UniPathway; UPA00159; UER00277. DR Proteomes; UP000239036; 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-UniRule. 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:UP000239036}; 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}; 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 292 535 Glutamine amidotransferase type-1. FT {ECO:0000259|PROSITE:PS51273}. FT NP_BIND 14 19 ATP. {ECO:0000256|HAMAP-Rule:MF_01227}. FT NP_BIND 148 150 Allosteric inhibitor CTP. FT {ECO:0000256|HAMAP-Rule:MF_01227}. FT NP_BIND 188 193 Allosteric inhibitor CTP; alternate. FT {ECO:0000256|HAMAP-Rule:MF_01227}. FT NP_BIND 188 193 UTP; alternate. {ECO:0000256|HAMAP-Rule: FT MF_01227}. FT REGION 1 267 Amidoligase domain. {ECO:0000256|HAMAP- FT Rule:MF_01227}. FT REGION 382 385 L-glutamine binding. {ECO:0000256|HAMAP- FT Rule:MF_01227}. FT ACT_SITE 381 381 Nucleophile. {ECO:0000256|PROSITE- FT ProRule:PRU00605}. FT ACT_SITE 381 381 Nucleophile; for glutamine hydrolysis. FT {ECO:0000256|HAMAP-Rule:MF_01227}. FT ACT_SITE 508 508 {ECO:0000256|HAMAP-Rule:MF_01227, FT ECO:0000256|PROSITE-ProRule:PRU00605}. FT ACT_SITE 510 510 {ECO:0000256|HAMAP-Rule:MF_01227, FT ECO:0000256|PROSITE-ProRule:PRU00605}. FT METAL 71 71 Magnesium. {ECO:0000256|HAMAP-Rule: FT MF_01227}. FT METAL 141 141 Magnesium. {ECO:0000256|HAMAP-Rule: FT MF_01227}. FT BINDING 13 13 Allosteric inhibitor CTP; alternate. FT {ECO:0000256|HAMAP-Rule:MF_01227}. FT BINDING 13 13 UTP; alternate. {ECO:0000256|HAMAP-Rule: FT MF_01227}. FT BINDING 54 54 L-glutamine. {ECO:0000256|HAMAP-Rule: FT MF_01227}. FT BINDING 71 71 ATP. {ECO:0000256|HAMAP-Rule:MF_01227}. FT BINDING 224 224 Allosteric inhibitor CTP; alternate. FT {ECO:0000256|HAMAP-Rule:MF_01227}. FT BINDING 224 224 UTP; alternate. {ECO:0000256|HAMAP-Rule: FT MF_01227}. FT BINDING 242 242 ATP. {ECO:0000256|HAMAP-Rule:MF_01227}. FT BINDING 354 354 L-glutamine; via carbonyl oxygen. FT {ECO:0000256|HAMAP-Rule:MF_01227}. FT BINDING 405 405 L-glutamine. {ECO:0000256|HAMAP-Rule: FT MF_01227}. FT BINDING 463 463 L-glutamine; via amide nitrogen. FT {ECO:0000256|HAMAP-Rule:MF_01227}. SQ SEQUENCE 536 AA; 59822 MW; 5BE1DDDB7A1C4C7C CRC64; MTKYIFVTGG VVSSIGKGIV AASLGRLLKN RGLKVTIQKF DPYINVDPGT MSPYQHGEVF VTDDGTETDL DLGHYERFID INLNKYSNVT TGKIYSEVLQ KERRGDYLGA TVQVIPHITN AIKEKIMRAG TTTDSDIVIT EIGGTVGDIE SLPFIEALRQ MKSDLGSDNV FYIHTTLIPY LRAAGEMKTK PTQHSVKELR SYGIQPNMLV VRTEQSITRE MRNKIASFCD VEPEAVIESL DVKTIYSIPL NVQKQNMDQI VLDHFEMQAP KADMSEWEDL ERHVQHLSRT IKIALVGKYV ALQDAYISVT EALKHAGYTD DAEIELNKIS AEDVTPENVQ ALLGDADGIL VPGGFGDRGI EGKITTIKYA RENDVPFLGI CLGMQMASVE FARDVLNLKT ANSTEIDPDT PDNIIDLMAD QEDVEEMGGT QRLGAYPCKL KPGTVAAKAY HNEEVVMERH RHRYEFNNEY REAMEAKGMV FSGTSPDNRL VEVIELPKQR FFVASQYHPE FLSRPNRPEG LFKAFIDAAN VTGTVK //