ID A0A6M9PVH0_9BURK Unreviewed; 553 AA. AC A0A6M9PVH0; DT 07-OCT-2020, integrated into UniProtKB/TrEMBL. DT 07-OCT-2020, sequence version 1. DT 29-SEP-2021, entry version 6. 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:QKM64709.1}; GN ORFNames=DCO17_05345 {ECO:0000313|EMBL:QKM64709.1}; OS Polynucleobacter sp. MWH-UH21B. OC Bacteria; Proteobacteria; Betaproteobacteria; Burkholderiales; OC Burkholderiaceae; Polynucleobacter; unclassified Polynucleobacter. OX NCBI_TaxID=1743174 {ECO:0000313|EMBL:QKM64709.1, ECO:0000313|Proteomes:UP000503312}; RN [1] {ECO:0000313|EMBL:QKM64709.1, ECO:0000313|Proteomes:UP000503312} RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=MWH-UH21B {ECO:0000313|EMBL:QKM64709.1, RC ECO:0000313|Proteomes:UP000503312}; RA Hahn M.W.; RT "Polynucleobacter sp. UH21B genome."; RL Submitted (APR-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|ARBA:ARBA00000314, 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; CP028942; QKM64709.1; -; Genomic_DNA. DR UniPathway; UPA00159; UER00277. DR Proteomes; UP000503312; 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; 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. 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 3..270 FT /note="CTP_synth_N" FT /evidence="ECO:0000259|Pfam:PF06418" FT DOMAIN 305..540 FT /note="GATase" FT /evidence="ECO:0000259|Pfam:PF00117" FT NP_BIND 14..19 FT /note="ATP" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT NP_BIND 151..153 FT /note="CTP; allosteric inhibitor" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT NP_BIND 191..196 FT /note="CTP; allosteric inhibitor; alternate" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT NP_BIND 191..196 FT /note="UTP; alternate" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT REGION 1..270 FT /note="Amidoligase domain" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT REGION 384..387 FT /note="L-glutamine binding" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT ACT_SITE 383 FT /note="Nucleophile; for glutamine hydrolysis" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT ACT_SITE 520 FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT ACT_SITE 522 FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT METAL 71 FT /note="Magnesium" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT METAL 144 FT /note="Magnesium" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT BINDING 13 FT /note="CTP; allosteric inhibitor; alternate" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT BINDING 13 FT /note="UTP; alternate" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT BINDING 71 FT /note="ATP" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT BINDING 227 FT /note="CTP; allosteric inhibitor; alternate" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT BINDING 227 FT /note="UTP; alternate" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT BINDING 245 FT /note="ATP" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT BINDING 356 FT /note="L-glutamine; via carbonyl oxygen" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT BINDING 407 FT /note="L-glutamine" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT BINDING 473 FT /note="L-glutamine; via amide nitrogen" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" SQ SEQUENCE 553 AA; 61282 MW; 92518B55AD4B3C96 CRC64; MTKYVFVTGG VVSSLGKGIA AASLAAILES RGLKVTLLKL DPYINVDPGT MSPLQHGEVF VTEDGAETDL DLGHYERFVS AKMRKSNNFT TGQIYESVIS KERRGEYLGK TVQVIPHITN EIQAFIERGA KASHDGKADV AICEIGGTVG DIESLPFLEA ARQMSIRLPK HSCAFVHLTL VPYINSAGEL KTKPTQHSVQ KLREIGIMPT VLLCRADRPI PDDERAKISL FSNVREEAVI SVWDVDTIYK IPEMLHSQGM DDLICRELEL NAKPADLSVW ANLVYELANP KHEVTIGMVG KYVELTESYK SLIEALRHAG IHTHTRVNIN YIDSEQIEKD GVGCLKELDA ILVPGGFGKR GTEGKIAAIR YARENNVPYL GICLGMQLAV IEFARHVANI AKANSTEFDA DTDSPVVALI TEWLDREGRV EKRTNDSDLG GTMRLGSQRC PIKPNTLAHR IYGAEVNERH RHRYEVNNVY VPKLEQAGLV ISARTPNESL PEMMELPESM HPWFFGVQFH PEFTSTPRDG HPLFSAFIKA ALVHQDAALK QVA //