ID A0A432F018_9BACT Unreviewed; 537 AA. AC A0A432F018; DT 08-MAY-2019, integrated into UniProtKB/TrEMBL. DT 08-MAY-2019, sequence version 1. DT 03-JUL-2019, entry version 3. 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 ECO:0000313|EMBL:RTZ64864.1}; GN ORFNames=DSZ35_09615 {ECO:0000313|EMBL:RTZ64864.1}; OS Verrucomicrobia bacterium. OC Bacteria; Verrucomicrobia; unclassified Verrucomicrobia. OX NCBI_TaxID=2026799 {ECO:0000313|EMBL:RTZ64864.1}; RN [1] {ECO:0000313|EMBL:RTZ64864.1} RP NUCLEOTIDE SEQUENCE. RC STRAIN=MAG 15 {ECO:0000313|EMBL:RTZ64864.1}; RA Trembath-Reichert E., Huber J.A.; RT "Combined omics and stable isotope probing to characterize newly RT discovered Mariana Back-Arc vent microbial communities."; RL Submitted (JUN-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 -!- 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:RTZ64864.1}. 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; QOAX01000264; RTZ64864.1; -; Genomic_DNA. DR UniPathway; UPA00159; UER00277. 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 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:RTZ64864.1}; 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 292 534 Glutamine amidotransferase type-1. FT {ECO:0000259|PROSITE:PS51273}. FT NP_BIND 13 18 ATP. {ECO:0000256|HAMAP-Rule:MF_01227}. FT NP_BIND 147 149 Allosteric inhibitor CTP. FT {ECO:0000256|HAMAP-Rule:MF_01227}. FT NP_BIND 187 192 Allosteric inhibitor CTP; alternate. FT {ECO:0000256|HAMAP-Rule:MF_01227}. FT NP_BIND 187 192 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 507 507 {ECO:0000256|HAMAP-Rule:MF_01227, FT ECO:0000256|PROSITE-ProRule:PRU00605}. FT ACT_SITE 509 509 {ECO:0000256|HAMAP-Rule:MF_01227, FT ECO:0000256|PROSITE-ProRule:PRU00605}. FT METAL 70 70 Magnesium. {ECO:0000256|HAMAP-Rule: FT MF_01227}. FT METAL 140 140 Magnesium. {ECO:0000256|HAMAP-Rule: FT MF_01227}. FT BINDING 12 12 Allosteric inhibitor CTP; alternate. FT {ECO:0000256|HAMAP-Rule:MF_01227}. FT BINDING 12 12 UTP; alternate. {ECO:0000256|HAMAP-Rule: FT MF_01227}. FT BINDING 70 70 ATP. {ECO:0000256|HAMAP-Rule:MF_01227}. FT BINDING 223 223 Allosteric inhibitor CTP; alternate. FT {ECO:0000256|HAMAP-Rule:MF_01227}. FT BINDING 223 223 UTP; alternate. {ECO:0000256|HAMAP-Rule: FT MF_01227}. FT BINDING 241 241 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 462 462 L-glutamine; via amide nitrogen. FT {ECO:0000256|HAMAP-Rule:MF_01227}. SQ SEQUENCE 537 AA; 59197 MW; ADA852C0E1E9A4A3 CRC64; MKHIFVTGGV VSSLGKGLTA ASIGTLLENR GLKVTLQKFD PYLNVDPGTM SPFQHGEVYV LDDGAETDLD LGHYERFTGT KLTRFNNLTS GQVYQSVLDK ERRGDYLGKT VQVIPHVTDE IQNRIREIGD KTGADVVITE IGGTIGDIEG LPFVEAIREF ALGAGRGNVL FLHVTFVPFI KAAGELKTKP TQQGVAKLRE IGITPDVLVC RCEKSLTKEL RQKLSLFCNV PYEAVIEEID VEHSIYEVPL MLQREGLDDL ICERLGLKTK PADMAHWREI IRKLITPRHR VRIGVVGKYV ELQDAYKSVY EAVIHGGVAN DCGVEIERVD AEDIEENGAA NALKGCSGIL VPGGFGERGT EGKILAARFA RENNIPYLGL CLGMQIATIE FARNVLKLEG AHSAEFDPGT AHPVIALLDE QQNVTDKGGT MRLGSQPCIL KPDSLVTRLY GAEEIHERHR HRYEFNNAYR EPFEAAGMMF SGTSPDGNLV EIVELTEHPF YVASQFHPEF KSKPNKPHPL FSGFIAAAHA CDHAKTV //