ID A0AA97G2Z0_9GAMM Unreviewed; 543 AA. AC A0AA97G2Z0; DT 27-MAR-2024, integrated into UniProtKB/TrEMBL. DT 27-MAR-2024, sequence version 1. DT 29-MAY-2024, entry version 2. 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 ORFNames=P6910_12770 {ECO:0000313|EMBL:WOG25458.1}; OS Endozoicomonas sp. 8E. OC Bacteria; Pseudomonadota; Gammaproteobacteria; Oceanospirillales; OC Endozoicomonadaceae; Endozoicomonas. OX NCBI_TaxID=3035692 {ECO:0000313|EMBL:WOG25458.1}; RN [1] {ECO:0000313|EMBL:WOG25458.1} RP NUCLEOTIDE SEQUENCE. RC STRAIN=8E {ECO:0000313|EMBL:WOG25458.1}; RA Chiou Y.-J., Chan Y.-F., Yu S.-P., Lu C.-Y., Hsiao S.S.-Y., Chiang P.-W., RA Hsu T.-C., Liu P.-Y., Wada N., Lee Y., Jane W.-N., Lee D.-C., Huang Y.-W., RA Tang S.-L.; RT "Novel coral bacterial species Ca. Endozoicomonas ruthgatesiae reveals RT differentiations in dddD gene mediated dimethylsulfoniopropionate (DMSP) RT metabolic regulation."; RL Submitted (MAR-2023) 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 --------------------------------------------------------------------------- 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; CP120717; WOG25458.1; -; Genomic_DNA. DR GO; GO:0016874; F:ligase activity; 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 {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..265 FT /note="CTP synthase N-terminal" FT /evidence="ECO:0000259|Pfam:PF06418" FT DOMAIN 300..533 FT /note="Glutamine amidotransferase" FT /evidence="ECO:0000259|Pfam:PF00117" FT REGION 1..265 FT /note="Amidoligase domain" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT ACT_SITE 378 FT /note="Nucleophile" FT /evidence="ECO:0000256|PROSITE-ProRule:PRU00605" FT ACT_SITE 378 FT /note="Nucleophile; for glutamine hydrolysis" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT ACT_SITE 514 FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227, FT ECO:0000256|PROSITE-ProRule:PRU00605" FT ACT_SITE 516 FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227, FT ECO:0000256|PROSITE-ProRule:PRU00605" FT BINDING 13 FT /ligand="CTP" FT /ligand_id="ChEBI:CHEBI:37563" FT /ligand_note="allosteric inhibitor" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT BINDING 13 FT /ligand="UTP" FT /ligand_id="ChEBI:CHEBI:46398" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT BINDING 14..19 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT BINDING 71 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT BINDING 71 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT BINDING 139 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000256|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:0000256|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:0000256|HAMAP-Rule:MF_01227" FT BINDING 186..191 FT /ligand="UTP" FT /ligand_id="ChEBI:CHEBI:46398" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT BINDING 222 FT /ligand="CTP" FT /ligand_id="ChEBI:CHEBI:37563" FT /ligand_note="allosteric inhibitor" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT BINDING 222 FT /ligand="UTP" FT /ligand_id="ChEBI:CHEBI:46398" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT BINDING 240 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT BINDING 351 FT /ligand="L-glutamine" FT /ligand_id="ChEBI:CHEBI:58359" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT BINDING 379..382 FT /ligand="L-glutamine" FT /ligand_id="ChEBI:CHEBI:58359" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT BINDING 402 FT /ligand="L-glutamine" FT /ligand_id="ChEBI:CHEBI:58359" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT BINDING 469 FT /ligand="L-glutamine" FT /ligand_id="ChEBI:CHEBI:58359" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" SQ SEQUENCE 543 AA; 60132 MW; DEFD5EE2119DBA9D CRC64; MTRYIFVTGG VVSSLGKGIA SASLAAILEA RGLKVTMLKL DPYINVDPGT MSPFQHGEVF VTEDGAETDL DLGHYERFVR TTMKQGNNFT TGRVYQDVLR KERRGDYLGG TVQVIPHITD EIKRRVVQGA GDADIAMVEI GGTVGDIESQ PFLEAIRQLK VELGSSRALL MHLTLVPYIK TAGETKTKPT QHSVKELRSI GLQPDILVCR SEQFIEASAR RKISLFTNVE ERAVISLEDA DTIYRIPQML HEQGLDQIVV DKFSLDTPAA DLSEWADVVD RDTHPEKEVT IAMVGKYMEL LDAYKSLIEA VRHAGLKTRT KVNIRYVDSE LLEQEGLSRL EGVSAILVPG GFGHRGVEGK VQAVRHAREN KIPYLGICLG MQVAVIEYAR NKAGLEGANS SEFDQNSEHP VIGLITEWLS SDGALETRTE ASDLGGTMRL GAQKCNLISG TQAHSAYGKD IVTERHRHRY EVNNNYLETL QDAGLVISGR SEDNALVEMV EVKEHPWFVA CQFHPEFTST PRDGHPLFKS FIEAALNYQA KQD //