ID PYRG_XANOM Reviewed; 554 AA. AC Q2P1K5; DT 12-DEC-2006, integrated into UniProtKB/Swiss-Prot. DT 07-FEB-2006, sequence version 1. DT 05-FEB-2025, entry version 105. 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=XOO2817; OS Xanthomonas oryzae pv. oryzae (strain MAFF 311018). OC Bacteria; Pseudomonadota; Gammaproteobacteria; Lysobacterales; OC Lysobacteraceae; Xanthomonas. OX NCBI_TaxID=342109; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=MAFF 311018; RA Ochiai H., Inoue Y., Takeya M., Sasaki A., Kaku H.; RT "Genome sequence of Xanthomonas oryzae pv. oryzae suggests contribution of RT large numbers of effector genes and insertion sequences to its race RT diversity."; RL Jpn. Agric. Res. Q. 39:275-287(2005). 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=UTP + L-glutamine + ATP + H2O = CTP + L-glutamate + ADP + CC phosphate + 2 H(+); 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=L-glutamine + H2O = 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=UTP + NH4(+) + ATP = CTP + ADP + phosphate + 2 H(+); 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; AP008229; BAE69572.1; -; Genomic_DNA. DR RefSeq; WP_011259532.1; NC_007705.1. DR AlphaFoldDB; Q2P1K5; -. DR SMR; Q2P1K5; -. DR MEROPS; C26.964; -. DR KEGG; xom:XOO2817; -. DR HOGENOM; CLU_011675_5_0_6; -. DR UniPathway; UPA00159; UER00277. DR GO; GO:0005829; C:cytosol; IEA:TreeGrafter. 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:0042802; F:identical protein binding; IEA:TreeGrafter. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0044210; P:'de novo' CTP biosynthetic process; IEA:UniProtKB-UniRule. DR GO; GO:0019856; P:pyrimidine nucleobase biosynthetic process; IEA:TreeGrafter. DR CDD; cd03113; CTPS_N; 1. DR CDD; cd01746; GATase1_CTP_Synthase; 1. DR FunFam; 3.40.50.300:FF:000009; CTP synthase; 1. DR FunFam; 3.40.50.880:FF:000002; 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..554 FT /note="CTP synthase" FT /id="PRO_0000266266" FT DOMAIN 292..545 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 380 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 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 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 353 FT /ligand="L-glutamine" FT /ligand_id="ChEBI:CHEBI:58359" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227" FT BINDING 381..384 FT /ligand="L-glutamine" FT /ligand_id="ChEBI:CHEBI:58359" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227" FT BINDING 404 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" SQ SEQUENCE 554 AA; 61559 MW; 23615CCFCE279B1B CRC64; MTPLIFVTGG VVSSLGKGIA AASLASILEA RGLKVTMMKL DPYINVDPGT MSPFQHGEVY VTDDGAETDL DLGHYERYVR TRLSRKNSVT TGRIYENVIR KERRGDYLGA TVQVIPHITD EIRRCIDEAT AGFDVALIEI GGTVGDIESL PFLEAIRQVR TERGAEKAMF MHLTLVPYIA AAGELKTKPT QHSVKELRSI GIQPDVLLCR SEQAVPDSER RKIALFTNVS ERAVISCPDI DVLYGMPLEL LRQGLDELVI VQFKLRDKVA AADLSEWAAV VDAVKHPLDE VTIAVVGKYV DHQDAYKSVA EALRHGGLRQ RTKVNLKWLE AQDLERSDMA ALQDIDGILV PGGFGDRGFE GKVQTSKFAR EHKVPYFGIC YGMQAAVVDY ARHVADLDAA NSTENDRQSP HPVIGLITEW RTATGEVEKR DEKSDLGGTM RLGLQEQRLK PGTLARELYG KDVVAERHRH RYEFNNRYRT QLEDAGLVIS GKSMDDTLVE VVELPRDTHP WFLACQAHPE FLSTPRDGHP LFIGFVRAAR EKKAGGKLLK EARA //