ID A0A3B6VA20_BRAHW Unreviewed; 538 AA. AC A0A3B6VA20; DT 05-DEC-2018, integrated into UniProtKB/TrEMBL. DT 05-DEC-2018, sequence version 1. DT 02-DEC-2020, entry version 7. 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 ECO:0000313|EMBL:ACN83390.1}; GN OrderedLocusNames=BHWA1_00899 {ECO:0000313|EMBL:ACN83390.1}; OS Brachyspira hyodysenteriae (strain ATCC 49526 / WA1). OC Bacteria; Spirochaetes; Brachyspirales; Brachyspiraceae; Brachyspira. OX NCBI_TaxID=565034 {ECO:0000313|EMBL:ACN83390.1, ECO:0000313|Proteomes:UP000001803}; RN [1] {ECO:0000313|EMBL:ACN83390.1, ECO:0000313|Proteomes:UP000001803} RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=ATCC 49526 / WA1 {ECO:0000313|Proteomes:UP000001803}; RX PubMed=19262690; DOI=10.1371/journal.pone.0004641; RA Bellgard M.I., Wanchanthuek P., La T., Ryan K., Moolhuijzen P., RA Albertyn Z., Shaban B., Motro Y., Dunn D.S., Schibeci D., Hunter A., RA Barrero R., Phillips N.D., Hampson D.J.; RT "Genome sequence of the pathogenic intestinal spirochete Brachyspira RT hyodysenteriae reveals adaptations to its lifestyle in the porcine large RT intestine."; RL PLoS ONE 4:E4641-E4641(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: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 -!- 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; CP001357; ACN83390.1; -; Genomic_DNA. DR RefSeq; WP_012670439.1; NC_012225.1. DR GeneID; 31722090; -. DR KEGG; bhy:BHWA1_00899; -. DR OMA; EFNNAYR; -. DR UniPathway; UPA00159; UER00277. DR Proteomes; UP000001803; 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: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-UniRule. DR CDD; cd01746; GATase1_CTP_Synthase; 1. DR Gene3D; 3.40.50.880; -; 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 PANTHER; PTHR11550; PTHR11550; 1. DR Pfam; PF06418; CTP_synth_N; 1. DR Pfam; PF00117; GATase; 1. DR SUPFAM; SSF52317; SSF52317; 1. DR SUPFAM; SSF52540; SSF52540; 1. DR TIGRFAMs; TIGR00337; PyrG; 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, ECO:0000256|PROSITE-ProRule:PRU00605}; 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 296..538 FT /note="Glutamine amidotransferase type-1" FT /evidence="ECO:0000259|PROSITE:PS51273" FT NP_BIND 15..20 FT /note="ATP" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT NP_BIND 149..151 FT /note="Allosteric inhibitor CTP" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT NP_BIND 189..194 FT /note="Allosteric inhibitor CTP; alternate" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT NP_BIND 189..194 FT /note="UTP; alternate" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT REGION 1..268 FT /note="Amidoligase domain" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT REGION 387..390 FT /note="L-glutamine binding" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT ACT_SITE 386 FT /note="Nucleophile" FT /evidence="ECO:0000256|PROSITE-ProRule:PRU00605" FT ACT_SITE 386 FT /note="Nucleophile; for glutamine hydrolysis" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT ACT_SITE 512 FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227, FT ECO:0000256|PROSITE-ProRule:PRU00605" FT ACT_SITE 514 FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227, FT ECO:0000256|PROSITE-ProRule:PRU00605" FT METAL 72 FT /note="Magnesium" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT METAL 142 FT /note="Magnesium" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT BINDING 14 FT /note="Allosteric inhibitor CTP; alternate" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT BINDING 14 FT /note="UTP; alternate" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT BINDING 72 FT /note="ATP" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT BINDING 225 FT /note="Allosteric inhibitor CTP; alternate" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT BINDING 225 FT /note="UTP; alternate" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT BINDING 359 FT /note="L-glutamine; via carbonyl oxygen" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT BINDING 410 FT /note="L-glutamine" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT BINDING 467 FT /note="L-glutamine; via amide nitrogen" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" SQ SEQUENCE 538 AA; 60906 MW; 395BF9AC7AA8E174 CRC64; MNTKYIFVTG GVVSGLGKGI TASSLGRLLK ARGLSVTIQK FDPYINLDPG TMSPFQHGEV FVTDDGAETD LDIGHYERFI DENLNKFSNV TTGKIYQHVI NMEREGKYLG ETVQVIPHIT NEIKRRIYRE NDTKKTDIVI TEIGGTIGDI ESLPYIEAIR QIKTELGQDN VLYIHVTLIP FISSSEEIKT KPTQHSVKEL MQSGIIPDIL VCRTSKHLQE SHKSKIALFC NLPKENVFEN FDEPNIYNVP IMLEAQGLSD VVCKHFKLQT AKIDLTDWTE LIIRQKKIST TNERVKIAIV GKYISMKDAY ISLIEALNHG GIYNDINVDM EWISAEELEN KDNIAEYFKN IHGLIIPGGF GERGIEGKIQ AIKYARENKI PYLGICLGMQ LMSVEFARNV LKLEDANTIE VKENAKNPII TIMEEQKKSI LKGGTMRLGA FDCDIKEGSL ANKLYGKTEI SERHRHRYEF NNEYIDVMEK AGFIVTGRMK NADLVEIVEI KDHPFMIAVQ FHPELKSRIT NPHPLFVGFI EAAKKLKA //