ID A0A2E3NED4_UNCDE Unreviewed; 543 AA. AC A0A2E3NED4; DT 31-JAN-2018, integrated into UniProtKB/TrEMBL. DT 31-JAN-2018, sequence version 1. DT 27-MAR-2024, entry version 27. 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:MBB82784.1}; GN ORFNames=CL931_03115 {ECO:0000313|EMBL:MBB82784.1}; OS Deltaproteobacteria bacterium. OC Bacteria; Myxococcota; Myxococcia. OX NCBI_TaxID=2026735 {ECO:0000313|EMBL:MBB82784.1, ECO:0000313|Proteomes:UP000229035}; RN [1] {ECO:0000313|Proteomes:UP000229035} RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Tully B.J., Graham E.D., Heidelberg J.F.; RT "The Reconstruction of 2,631 Draft Metagenome-Assembled Genomes from the RT Global Oceans."; RL Submitted (SEP-2017) 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 -!- CAUTION: The sequence shown here is derived from an EMBL/GenBank/DDBJ CC whole genome shotgun (WGS) entry which is preliminary data. CC {ECO:0000313|EMBL:MBB82784.1}. 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; PAQX01000015; MBB82784.1; -; Genomic_DNA. DR AlphaFoldDB; A0A2E3NED4; -. DR UniPathway; UPA00159; UER00277. DR Proteomes; UP000229035; 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:0004359; F:glutaminase activity; IEA:RHEA. 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; 3.40.50.880; -; 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 NCBIfam; TIGR00337; PyrG; 1. 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 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 7..269 FT /note="CTP synthase N-terminal" FT /evidence="ECO:0000259|Pfam:PF06418" FT DOMAIN 305..525 FT /note="Glutamine amidotransferase" FT /evidence="ECO:0000259|Pfam:PF00117" FT REGION 1..269 FT /note="Amidoligase domain" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT ACT_SITE 380 FT /note="Nucleophile" FT /evidence="ECO:0000256|PROSITE-ProRule:PRU00605" FT ACT_SITE 380 FT /note="Nucleophile; for glutamine hydrolysis" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT ACT_SITE 506 FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227, FT ECO:0000256|PROSITE-ProRule:PRU00605" FT ACT_SITE 508 FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227, FT ECO:0000256|PROSITE-ProRule:PRU00605" FT BINDING 17 FT /ligand="CTP" FT /ligand_id="ChEBI:CHEBI:37563" FT /ligand_note="allosteric inhibitor" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT BINDING 17 FT /ligand="UTP" FT /ligand_id="ChEBI:CHEBI:46398" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT BINDING 18..23 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT BINDING 75 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT BINDING 75 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT BINDING 143 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT BINDING 150..152 FT /ligand="CTP" FT /ligand_id="ChEBI:CHEBI:37563" FT /ligand_note="allosteric inhibitor" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT BINDING 190..195 FT /ligand="CTP" FT /ligand_id="ChEBI:CHEBI:37563" FT /ligand_note="allosteric inhibitor" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT BINDING 190..195 FT /ligand="UTP" FT /ligand_id="ChEBI:CHEBI:46398" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT BINDING 226 FT /ligand="CTP" FT /ligand_id="ChEBI:CHEBI:37563" FT /ligand_note="allosteric inhibitor" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT BINDING 226 FT /ligand="UTP" FT /ligand_id="ChEBI:CHEBI:46398" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT BINDING 242..244 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT BINDING 353 FT /ligand="L-glutamine" FT /ligand_id="ChEBI:CHEBI:58359" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT BINDING 381..384 FT /ligand="L-glutamine" FT /ligand_id="ChEBI:CHEBI:58359" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT BINDING 404 FT /ligand="L-glutamine" FT /ligand_id="ChEBI:CHEBI:58359" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT BINDING 461 FT /ligand="L-glutamine" FT /ligand_id="ChEBI:CHEBI:58359" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" SQ SEQUENCE 543 AA; 59683 MW; 9D0D5BAB7F7CFCB4 CRC64; MSPRPTKYIF VTGGVMSSLG KGLASASIGA LLEARSLKVT FLKLDPYLNV DPGTMNPFQH GEVYVTEDGA ETDLDLGHYE RFTTTVLGQV NNMTAGRIYD QVLSAERRGD YLGGTVQVIP HVTDAIKGAI RGASQDCDVI LVEIGGTVGD IESLPFLEAI RQFRADAGRE NCCFIHVAPV LYQSTAGEVK TKPVQHSVKE LQSVGLAPDI ILCRTDRFLE KGIKSKIALF CNVDEDAVIT AKDVSSIYEV PLAFAKENLD EKIAQVLNMW TGRPDLRHWE RLFNVQQNPE KQIKIAMVGK YVDLTESYKS LNEALYHGGF ACGNEVVIEY VDSEKLEDTT ILGGYDGICV PHGFGSRGVE GKIRAIEYVR KNEIPFLGIC LGMQMACIEF GRNVVGLEGA NSSEMVDDSP HPVIDILPEQ KEVEDLGGTM RLGAYPCVLQ PGSKAAEAYG ALEISERHRH RWEFNEDYKD RFQAAGMLFS GSSPDGRLVE VVEIPSHPFF VASQFHPEFK SKPFDPHPLF EAFVRAASKR HGEGSKASAA EAE //