ID A0A3B6VA20_BRAHW Unreviewed; 538 AA. AC A0A3B6VA20; DT 05-DEC-2018, integrated into UniProtKB/TrEMBL. DT 05-DEC-2018, sequence version 1. DT 13-FEB-2019, entry version 3. 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 RT large 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|HAMAP-Rule:MF_01227, CC ECO:0000256|SAAS:SAAS01116648}; CC -!- ACTIVITY REGULATION: Allosterically activated by GTP, when CC glutamine is the substrate; GTP has no effect on the reaction when CC ammonia is the substrate. The allosteric effector GTP functions by CC stabilizing the protein conformation that binds the tetrahedral CC intermediate(s) formed during glutamine hydrolysis. Inhibited by CC the product CTP, via allosteric rather than competitive CC inhibition. {ECO:0000256|HAMAP-Rule:MF_01227}. CC -!- PATHWAY: Pyrimidine metabolism; CTP biosynthesis via de novo CC pathway; CTP from UDP: step 2/2. {ECO:0000256|HAMAP-Rule:MF_01227, CC ECO:0000256|SAAS:SAAS00710815}. CC -!- SUBUNIT: Homotetramer. {ECO:0000256|HAMAP-Rule:MF_01227, CC ECO:0000256|SAAS:SAAS00710816}. CC -!- MISCELLANEOUS: CTPSs have evolved a hybrid strategy for CC distinguishing between UTP and CTP. The overlapping regions of the CC product feedback inhibitory and substrate sites recognize a common CC feature in both compounds, the triphosphate moiety. To CC differentiate isosteric substrate and product pyrimidine rings, an CC additional pocket far from the expected kinase/ligase catalytic CC site, specifically recognizes the cytosine and ribose portions of CC the product inhibitor. {ECO:0000256|HAMAP-Rule:MF_01227}. CC -!- SIMILARITY: Belongs to the CTP synthase family. CC {ECO:0000256|HAMAP-Rule:MF_01227, ECO:0000256|SAAS:SAAS00710794}. CC -!- CAUTION: Lacks conserved residue(s) required for the propagation CC of 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 KO; K01937; -. 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|HAMAP-Rule:MF_01227, KW ECO:0000256|SAAS:SAAS00710699}; KW Complete proteome {ECO:0000313|Proteomes:UP000001803}; KW Glutamine amidotransferase {ECO:0000256|HAMAP-Rule:MF_01227, KW ECO:0000256|PROSITE-ProRule:PRU00605, ECO:0000256|SAAS:SAAS00710676}; KW Ligase {ECO:0000256|HAMAP-Rule:MF_01227, KW ECO:0000256|SAAS:SAAS00710762}; KW Magnesium {ECO:0000256|HAMAP-Rule:MF_01227, KW ECO:0000256|SAAS:SAAS00710689}; KW Metal-binding {ECO:0000256|HAMAP-Rule:MF_01227, KW ECO:0000256|SAAS:SAAS00710675}; KW Nucleotide-binding {ECO:0000256|HAMAP-Rule:MF_01227, KW ECO:0000256|SAAS:SAAS00710810}; KW Pyrimidine biosynthesis {ECO:0000256|HAMAP-Rule:MF_01227, KW ECO:0000256|SAAS:SAAS00710748}. FT DOMAIN 296 538 Glutamine amidotransferase type-1. FT {ECO:0000259|PROSITE:PS51273}. FT NP_BIND 15 20 ATP. {ECO:0000256|HAMAP-Rule:MF_01227}. FT NP_BIND 149 151 Allosteric inhibitor CTP. FT {ECO:0000256|HAMAP-Rule:MF_01227}. FT NP_BIND 189 194 Allosteric inhibitor CTP; alternate. FT {ECO:0000256|HAMAP-Rule:MF_01227}. FT NP_BIND 189 194 UTP; alternate. {ECO:0000256|HAMAP-Rule: FT MF_01227}. FT REGION 1 268 Amidoligase domain. {ECO:0000256|HAMAP- FT Rule:MF_01227}. FT REGION 387 390 L-glutamine binding. {ECO:0000256|HAMAP- FT Rule:MF_01227}. FT ACT_SITE 386 386 Nucleophile. {ECO:0000256|PROSITE- FT ProRule:PRU00605}. FT ACT_SITE 386 386 Nucleophile; for glutamine hydrolysis. FT {ECO:0000256|HAMAP-Rule:MF_01227}. FT ACT_SITE 512 512 {ECO:0000256|HAMAP-Rule:MF_01227, FT ECO:0000256|PROSITE-ProRule:PRU00605}. FT ACT_SITE 514 514 {ECO:0000256|HAMAP-Rule:MF_01227, FT ECO:0000256|PROSITE-ProRule:PRU00605}. FT METAL 72 72 Magnesium. {ECO:0000256|HAMAP-Rule: FT MF_01227}. FT METAL 142 142 Magnesium. {ECO:0000256|HAMAP-Rule: FT MF_01227}. FT BINDING 14 14 Allosteric inhibitor CTP; alternate. FT {ECO:0000256|HAMAP-Rule:MF_01227}. FT BINDING 14 14 UTP; alternate. {ECO:0000256|HAMAP-Rule: FT MF_01227}. FT BINDING 72 72 ATP. {ECO:0000256|HAMAP-Rule:MF_01227}. FT BINDING 225 225 Allosteric inhibitor CTP; alternate. FT {ECO:0000256|HAMAP-Rule:MF_01227}. FT BINDING 225 225 UTP; alternate. {ECO:0000256|HAMAP-Rule: FT MF_01227}. FT BINDING 359 359 L-glutamine; via carbonyl oxygen. FT {ECO:0000256|HAMAP-Rule:MF_01227}. FT BINDING 410 410 L-glutamine. {ECO:0000256|HAMAP-Rule: FT MF_01227}. FT BINDING 467 467 L-glutamine; via amide nitrogen. FT {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 //