AC MF_01227; DC Protein; auto TR HAMAP; MF_01227; -; 1; level=0 XX Names: PyrG XX ID PYRG DE RecName: Full=CTP synthase; DE EC=6.3.4.2; DE AltName: Full=Cytidine 5'-triphosphate synthase; DE AltName: Full=Cytidine triphosphate synthetase; DE Short=CTP synthetase; DE Short=CTPS; DE AltName: Full=UTP--ammonia ligase; GN Name=pyrG; XX 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. 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 -!- 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; 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; 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. CC -!- PATHWAY: Pyrimidine metabolism; CTP biosynthesis via de novo pathway; CC CTP from UDP: step 2/2. CC -!- SUBUNIT: Homotetramer. 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 -!- SIMILARITY: Belongs to the CTP synthase family. XX DR Pfam; PF06418; CTP_synth_N; 1; trigger=no DR Pfam; PF00117; GATase; 1; trigger=no DR NCBIfam; TIGR00337; PyrG; 1; trigger=no DR PROSITE; PS51273; GATASE_TYPE_1; 1; trigger=yes XX KW ATP-binding KW Glutamine amidotransferase KW Ligase KW Magnesium KW Metal-binding KW Nucleotide-binding KW Pyrimidine biosynthesis XX GO GO:0003883; F:CTP synthase activity GO GO:0006221; P:pyrimidine nucleotide biosynthetic process XX FT From: PYRG_ECOLI (P0A7E5) FT BINDING 15..20 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT Condition: x-x-G-K-G-x FT BINDING 147..149 FT /ligand="CTP" FT /ligand_id="ChEBI:CHEBI:37563" FT /ligand_note="allosteric inhibitor" FT Condition: D-x-E FT BINDING 187..192 FT /ligand="CTP" FT /ligand_id="ChEBI:CHEBI:37563" FT /ligand_note="allosteric inhibitor" FT Condition: K-[TS]-K-x-x-Q FT BINDING 187..192 FT /ligand="UTP" FT /ligand_id="ChEBI:CHEBI:46398" FT Condition: K-[TS]-K-x-x-Q FT BINDING 239..241 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT Optional; Condition: [KR]-x-[VALI] case not FT BINDING 241 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT Optional; Condition: [VALI] end case FT REGION Nter..266 FT /note="Amidoligase domain" FT BINDING 380..383 FT /ligand="L-glutamine" FT /ligand_id="ChEBI:CHEBI:58359" FT Condition: [LMYF]-x-x-[QH] FT ACT_SITE 379 FT /note="Nucleophile; for glutamine hydrolysis" FT Condition: C FT ACT_SITE 515 FT Condition: H FT ACT_SITE 517 FT Condition: E FT BINDING 72 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT Condition: D FT BINDING 140 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT Condition: E FT BINDING 14 FT /ligand="CTP" FT /ligand_id="ChEBI:CHEBI:37563" FT /ligand_note="allosteric inhibitor" FT Condition: S FT BINDING 14 FT /ligand="UTP" FT /ligand_id="ChEBI:CHEBI:46398" FT Condition: S FT BINDING 55 FT /ligand="L-glutamine" FT /ligand_id="ChEBI:CHEBI:58359" FT Optional; Condition: Y FT BINDING 72 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT Condition: D FT BINDING 223 FT /ligand="CTP" FT /ligand_id="ChEBI:CHEBI:37563" FT /ligand_note="allosteric inhibitor" FT Condition: [KR] FT BINDING 223 FT /ligand="UTP" FT /ligand_id="ChEBI:CHEBI:46398" FT Condition: [KR] FT BINDING 352 FT /ligand="L-glutamine" FT /ligand_id="ChEBI:CHEBI:58359" FT Condition: [GA] FT BINDING 403 FT /ligand="L-glutamine" FT /ligand_id="ChEBI:CHEBI:58359" FT Condition: E FT BINDING 470 FT /ligand="L-glutamine" FT /ligand_id="ChEBI:CHEBI:58359" FT Condition: R XX Size: 524-608; Related: None; Template: P0A7E5; P28595; Q59321; O87761; P9WHK7; Q5SIA8; Q980S6; Scope: Bacteria Archaea Fusion: Nter: None Cter: None Duplicate: None Plasmid: None Comments: RPE1 type insert in RICPR and weird insertion in TREPA; sequences not shown in alignment. Divergent UREPA; sequence not included in alignment. XX # Revision 1.37 2023/06/01 //