ID PYRG_FIBSS Reviewed; 563 AA. AC Q939R0; C9RS78; D9S4K4; DT 19-OCT-2002, integrated into UniProtKB/Swiss-Prot. DT 19-JAN-2010, sequence version 2. DT 27-MAR-2024, entry version 112. 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}; GN OrderedLocusNames=Fisuc_1822, FSU_2325; OS Fibrobacter succinogenes (strain ATCC 19169 / S85). OC Bacteria; Fibrobacterota; Fibrobacteria; Fibrobacterales; Fibrobacteraceae; OC Fibrobacter. OX NCBI_TaxID=59374; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=ATCC 19169 / S85; RG US DOE Joint Genome Institute; RA Lucas S., Copeland A., Lapidus A., Glavina del Rio T., Tice H., Bruce D., RA Goodwin L., Pitluck S., Chertkov O., Detter J.C., Han C., Tapia R., RA Larimer F., Land M., Hauser L., Kyrpides N., Mikhailova N., Weimer P.J., RA Stevenson D.M., Boyum J., Brumm P.I., Mead D.; RT "Complete sequence of Fibrobacter succinogenes subsp. succinogenes S85."; RL Submitted (OCT-2009) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=ATCC 19169 / S85; RA Durkin A.S., Nelson K.E., Morrison M., Forsberg C.W., Wilson D.B., RA Russell J.B., Cann I.K.O., Mackie R.I., White B.A.; RT "Complete sequence of Fibrobacter succinogenes subsp. succinogenes S85."; RL Submitted (AUG-2010) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 388-520. RX PubMed=11535801; DOI=10.1099/00221287-147-9-2611; RA Griffiths E., Gupta R.S.; RT "The use of signature sequences in different proteins to determine the RT relative branching order of bacterial divisions: evidence that Fibrobacter RT diverged at a similar time to Chlamydia and the Cytophaga-Flavobacterium- RT Bacteroides division."; RL Microbiology 147:2611-2622(2001). 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; CP001792; ACX75414.1; -; Genomic_DNA. DR EMBL; CP002158; ADL27373.1; -; Genomic_DNA. DR EMBL; AY017383; AAK13023.1; -; Genomic_DNA. DR RefSeq; WP_014546486.1; NC_017448.1. DR AlphaFoldDB; Q939R0; -. DR SMR; Q939R0; -. DR STRING; 59374.FSU_2325; -. DR MEROPS; C26.964; -. DR GeneID; 34756163; -. DR KEGG; fsc:FSU_2325; -. DR KEGG; fsu:Fisuc_1822; -. DR PATRIC; fig|59374.8.peg.2235; -. DR eggNOG; COG0504; Bacteria. DR HOGENOM; CLU_011675_5_0_0; -. DR OrthoDB; 9801107at2; -. DR UniPathway; UPA00159; UER00277. DR Proteomes; UP000000517; 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. FT CHAIN 1..563 FT /note="CTP synthase" FT /id="PRO_0000138186" FT DOMAIN 303..545 FT /note="Glutamine amidotransferase type-1" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227" FT REGION 1..278 FT /note="Amidoligase domain" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227" FT REGION 542..563 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 390 FT /note="Nucleophile; for glutamine hydrolysis" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227" FT ACT_SITE 518 FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227" FT ACT_SITE 520 FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227" FT BINDING 24 FT /ligand="CTP" FT /ligand_id="ChEBI:CHEBI:37563" FT /ligand_note="allosteric inhibitor" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227" FT BINDING 24 FT /ligand="UTP" FT /ligand_id="ChEBI:CHEBI:46398" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227" FT BINDING 25..30 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227" FT BINDING 65 FT /ligand="L-glutamine" FT /ligand_id="ChEBI:CHEBI:58359" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227" FT BINDING 82 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227" FT BINDING 82 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227" FT BINDING 151 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227" FT BINDING 158..160 FT /ligand="CTP" FT /ligand_id="ChEBI:CHEBI:37563" FT /ligand_note="allosteric inhibitor" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227" FT BINDING 198..203 FT /ligand="CTP" FT /ligand_id="ChEBI:CHEBI:37563" FT /ligand_note="allosteric inhibitor" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227" FT BINDING 198..203 FT /ligand="UTP" FT /ligand_id="ChEBI:CHEBI:46398" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227" FT BINDING 234 FT /ligand="CTP" FT /ligand_id="ChEBI:CHEBI:37563" FT /ligand_note="allosteric inhibitor" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227" FT BINDING 234 FT /ligand="UTP" FT /ligand_id="ChEBI:CHEBI:46398" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227" FT BINDING 250..252 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227" FT BINDING 363 FT /ligand="L-glutamine" FT /ligand_id="ChEBI:CHEBI:58359" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227" FT BINDING 391..394 FT /ligand="L-glutamine" FT /ligand_id="ChEBI:CHEBI:58359" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227" FT BINDING 414 FT /ligand="L-glutamine" FT /ligand_id="ChEBI:CHEBI:58359" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227" FT BINDING 471 FT /ligand="L-glutamine" FT /ligand_id="ChEBI:CHEBI:58359" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227" FT CONFLICT 395..397 FT /note="CCV -> MLA (in Ref. 3; AAK13023)" FT /evidence="ECO:0000305" FT CONFLICT 403 FT /note="D -> N (in Ref. 3; AAK13023)" FT /evidence="ECO:0000305" FT CONFLICT 407..409 FT /note="WKD -> LKV (in Ref. 3; AAK13023)" FT /evidence="ECO:0000305" FT CONFLICT 421..428 FT /note="HPVIDLMD -> PRFIRDLE (in Ref. 3; AAK13023)" FT /evidence="ECO:0000305" FT CONFLICT 432..435 FT /note="NVTE -> DGHD (in Ref. 3; AAK13023)" FT /evidence="ECO:0000305" FT CONFLICT 444 FT /note="A -> L (in Ref. 3; AAK13023)" FT /evidence="ECO:0000305" FT CONFLICT 457..458 FT /note="KL -> NV (in Ref. 3; AAK13023)" FT /evidence="ECO:0000305" FT CONFLICT 461 FT /note="S -> R (in Ref. 3; AAK13023)" FT /evidence="ECO:0000305" FT CONFLICT 465 FT /note="S -> T (in Ref. 3; AAK13023)" FT /evidence="ECO:0000305" SQ SEQUENCE 563 AA; 62460 MW; 768352B39EE391D6 CRC64; MAKATAKNSA KQPKYIFITG GVVSSLGKGI TSASLALLLK SRGYKVFMQK LDPYLNVDPG TMSPYQHGEV FVTDDGYETD LDLGHYERFA GVQCSKASSY TSGRIYSSVL SKERAGHYLG GTVQVIPHIT NEIKDAFRSA AESGADIILC EIGGVAGDIE SLPFLEAARQ FRFEVGVENT CFIHLTLVPY LKAAGELKTK PSQHSVAELR NIGIFPDILV CRTEMHIPQE HLDKLALFCN VKPECVIEEK DVKDSVYAVP RELSKQELDL RVLEQLHLSV HPIVHSEWDS LVKKATQPKY ECTIALVGKY IAIRDAYKSV HEALQHAGMA NNAKVNVECI EAEELEKNPK LIKKADGILI PGGFGSRGVN GKCAAIRYAR ENKVPLLGIC LGMQCCVIEF ARDVLGWKDA NSTEFDENTT HPVIDLMDEQ KNVTEKGGTM RLGAYPCKLA KDSNAAKLYK SEKISERHRH RYEFNYNSEF RKELEKAGLK IAGTSPDGKL VEMVELKNHP YFEACQFHPE FKSRPTDPHP LFTGLVKAAL EQKKANGKKP TAPSEKTKKT KTK //