ID PYRG_SPHAL Reviewed; 543 AA. AC Q1GTY6; DT 12-DEC-2006, integrated into UniProtKB/Swiss-Prot. DT 27-JUN-2006, sequence version 1. DT 24-JAN-2024, entry version 101. DE RecName: Full=CTP synthase {ECO:0000255|HAMAP-Rule:MF_01227}; DE EC=6.3.4.2 {ECO:0000255|HAMAP-Rule:MF_01227}; DE AltName: Full=Cytidine 5'-triphosphate synthase {ECO:0000255|HAMAP-Rule:MF_01227}; DE AltName: Full=Cytidine triphosphate synthetase {ECO:0000255|HAMAP-Rule:MF_01227}; DE Short=CTP synthetase {ECO:0000255|HAMAP-Rule:MF_01227}; DE Short=CTPS {ECO:0000255|HAMAP-Rule:MF_01227}; DE AltName: Full=UTP--ammonia ligase {ECO:0000255|HAMAP-Rule:MF_01227}; GN Name=pyrG {ECO:0000255|HAMAP-Rule:MF_01227}; OrderedLocusNames=Sala_1170; OS Sphingopyxis alaskensis (strain DSM 13593 / LMG 18877 / RB2256) OS (Sphingomonas alaskensis). OC Bacteria; Pseudomonadota; Alphaproteobacteria; Sphingomonadales; OC Sphingomonadaceae; Sphingopyxis. OX NCBI_TaxID=317655; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=DSM 13593 / LMG 18877 / RB2256; RX PubMed=19805210; DOI=10.1073/pnas.0903507106; RA Lauro F.M., McDougald D., Thomas T., Williams T.J., Egan S., Rice S., RA DeMaere M.Z., Ting L., Ertan H., Johnson J., Ferriera S., Lapidus A., RA Anderson I., Kyrpides N., Munk A.C., Detter C., Han C.S., Brown M.V., RA Robb F.T., Kjelleberg S., Cavicchioli R.; RT "The genomic basis of trophic strategy in marine bacteria."; RL Proc. Natl. Acad. Sci. U.S.A. 106:15527-15533(2009). 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:0000255|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:0000255|HAMAP-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:0000255|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:0000255|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:0000255|HAMAP- CC Rule:MF_01227}. CC -!- PATHWAY: Pyrimidine metabolism; CTP biosynthesis via de novo pathway; CC CTP from UDP: step 2/2. {ECO:0000255|HAMAP-Rule:MF_01227}. CC -!- SUBUNIT: Homotetramer. {ECO:0000255|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:0000255|HAMAP-Rule:MF_01227}. CC -!- SIMILARITY: Belongs to the CTP synthase family. {ECO:0000255|HAMAP- CC 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; CP000356; ABF52886.1; -; Genomic_DNA. DR RefSeq; WP_011541471.1; NC_008048.1. DR AlphaFoldDB; Q1GTY6; -. DR SMR; Q1GTY6; -. DR STRING; 317655.Sala_1170; -. DR MEROPS; C26.964; -. DR KEGG; sal:Sala_1170; -. DR eggNOG; COG0504; Bacteria. DR HOGENOM; CLU_011675_5_0_5; -. DR OMA; EFNNAYR; -. DR OrthoDB; 9801107at2; -. DR UniPathway; UPA00159; UER00277. DR Proteomes; UP000006578; 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: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-KW. 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; Glutamine amidotransferase; Ligase; Magnesium; Metal-binding; KW Nucleotide-binding; Pyrimidine biosynthesis; Reference proteome. FT CHAIN 1..543 FT /note="CTP synthase" FT /id="PRO_0000266223" FT DOMAIN 291..542 FT /note="Glutamine amidotransferase type-1" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227" FT REGION 1..265 FT /note="Amidoligase domain" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227" FT ACT_SITE 381 FT /note="Nucleophile; for glutamine hydrolysis" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227" FT ACT_SITE 515 FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227" FT ACT_SITE 517 FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227" FT BINDING 13 FT /ligand="CTP" FT /ligand_id="ChEBI:CHEBI:37563" FT /ligand_note="allosteric inhibitor" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227" FT BINDING 13 FT /ligand="UTP" FT /ligand_id="ChEBI:CHEBI:46398" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227" FT BINDING 14..19 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227" FT BINDING 54 FT /ligand="L-glutamine" FT /ligand_id="ChEBI:CHEBI:58359" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227" FT BINDING 71 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227" FT BINDING 71 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227" FT BINDING 139 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227" FT BINDING 146..148 FT /ligand="CTP" FT /ligand_id="ChEBI:CHEBI:37563" FT /ligand_note="allosteric inhibitor" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227" FT BINDING 186..191 FT /ligand="CTP" FT /ligand_id="ChEBI:CHEBI:37563" FT /ligand_note="allosteric inhibitor" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227" FT BINDING 186..191 FT /ligand="UTP" FT /ligand_id="ChEBI:CHEBI:46398" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227" FT BINDING 222 FT /ligand="CTP" FT /ligand_id="ChEBI:CHEBI:37563" FT /ligand_note="allosteric inhibitor" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227" FT BINDING 222 FT /ligand="UTP" FT /ligand_id="ChEBI:CHEBI:46398" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227" FT BINDING 354 FT /ligand="L-glutamine" FT /ligand_id="ChEBI:CHEBI:58359" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227" FT BINDING 382..385 FT /ligand="L-glutamine" FT /ligand_id="ChEBI:CHEBI:58359" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227" FT BINDING 405 FT /ligand="L-glutamine" FT /ligand_id="ChEBI:CHEBI:58359" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227" FT BINDING 470 FT /ligand="L-glutamine" FT /ligand_id="ChEBI:CHEBI:58359" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227" SQ SEQUENCE 543 AA; 59457 MW; B33AAC32224CA804 CRC64; MARFIFITGG VVSSLGKGLM AASLAALLQA RGYRVRIRKF DPYLNVDPGT MSPYQHGEVY VTDDGAETDL DLGHYERFTG VAARQSDNVT SGRIYQGIIA KERRGDYLGA TVQVVPHVTD AIKDFARAET DDLDFVLCEI GGTVGDIESL PFIEAIRQLK NEVGRDNAIS VHVTLVPYIA AAGELKTKPT QHSVRELASL GVQPDILLCR CEKPLPDSER AKIALFCNVR KEAVIPALDA DSIYSVPVQY HGEGLDSEVL RAFGILDAPA PDLTAWYDIM DRKQHPEGEV TIGVVGKYVS LPDAYKSLNE ALVHGGMAHR VKVNIRWLDA EMFERDEDLV ANLEPLHGIL VPGGFGERGS EGKIASVRFA RERNVPFFGI CLGMQMACIE AARNTSGIAN ASSTEFGPTD EPVVGLITEW MSAEGLQKRG ANTDLGGTMR LGAYDAKLSP NSHVASVYGT NEISERHRHR YEVNGAYRER LEKGGLVFSG MSPDGMLPEI VERPDHPWFI GVQFHPELKS KPFDPHPLFA GFIEAAVKQS RLV //