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 12-SEP-2018, entry version 88. 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; Fibrobacteres; 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., RA Bruce D., Goodwin L., Pitluck S., Chertkov O., Detter J.C., Han C., RA Tapia R., Larimer F., Land M., Hauser L., Kyrpides N., Mikhailova N., RA Weimer P.J., Stevenson D.M., Boyum J., Brumm P.I., Mead D.; RT "Complete sequence of Fibrobacter succinogenes subsp. succinogenes RT 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 RT S85."; RL Submitted (AUG-2010) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 388-520. RX PubMed=11535801; 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 RT Fibrobacter diverged at a similar time to Chlamydia and the Cytophaga- RT Flavobacterium-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: ATP + UTP + L-glutamine = ADP + phosphate + CC CTP + L-glutamate. {ECO:0000255|HAMAP-Rule:MF_01227}. 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:0000255|HAMAP-Rule:MF_01227}. CC -!- PATHWAY: Pyrimidine metabolism; CTP biosynthesis via de novo CC pathway; CTP from UDP: step 2/2. {ECO:0000255|HAMAP- CC Rule:MF_01227}. CC -!- SUBUNIT: Homotetramer. {ECO:0000255|HAMAP-Rule:MF_01227}. 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:0000255|HAMAP-Rule:MF_01227}. CC -!- SIMILARITY: Belongs to the CTP synthase family. CC {ECO:0000255|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; 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 ProteinModelPortal; Q939R0; -. DR SMR; Q939R0; -. DR STRING; 59374.Fisuc_1822; -. DR MEROPS; C26.964; -. DR PRIDE; Q939R0; -. DR EnsemblBacteria; ACX75414; ACX75414; Fisuc_1822. DR EnsemblBacteria; ADL27373; ADL27373; FSU_2325. DR GeneID; 34756163; -. DR KEGG; fsc:FSU_2325; -. DR KEGG; fsu:Fisuc_1822; -. DR PATRIC; fig|59374.8.peg.2235; -. DR eggNOG; ENOG4105C8D; Bacteria. DR eggNOG; COG0504; LUCA. DR HOGENOM; HOG000077515; -. DR KO; K01937; -. DR OMA; EFNNAYR; -. DR BioCyc; FSUC59374:G1GMS-2227-MONOMER; -. 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-EC. 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; 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; Complete proteome; Glutamine amidotransferase; Ligase; KW Magnesium; Metal-binding; Nucleotide-binding; Pyrimidine biosynthesis; KW Reference proteome. FT CHAIN 1 563 CTP synthase. FT /FTId=PRO_0000138186. FT DOMAIN 303 545 Glutamine amidotransferase type-1. FT {ECO:0000255|HAMAP-Rule:MF_01227}. FT NP_BIND 25 30 ATP. {ECO:0000255|HAMAP-Rule:MF_01227}. FT NP_BIND 158 160 Allosteric inhibitor CTP. FT {ECO:0000255|HAMAP-Rule:MF_01227}. FT NP_BIND 198 203 Allosteric inhibitor CTP; alternate. FT {ECO:0000255|HAMAP-Rule:MF_01227}. FT NP_BIND 198 203 UTP; alternate. {ECO:0000255|HAMAP- FT Rule:MF_01227}. FT NP_BIND 250 252 ATP. {ECO:0000255|HAMAP-Rule:MF_01227}. FT REGION 1 278 Amidoligase domain. {ECO:0000255|HAMAP- FT Rule:MF_01227}. FT REGION 391 394 L-glutamine binding. {ECO:0000255|HAMAP- FT Rule:MF_01227}. FT ACT_SITE 390 390 Nucleophile; for glutamine hydrolysis. FT {ECO:0000255|HAMAP-Rule:MF_01227}. FT ACT_SITE 518 518 {ECO:0000255|HAMAP-Rule:MF_01227}. FT ACT_SITE 520 520 {ECO:0000255|HAMAP-Rule:MF_01227}. FT METAL 82 82 Magnesium. {ECO:0000255|HAMAP- FT Rule:MF_01227}. FT METAL 151 151 Magnesium. {ECO:0000255|HAMAP- FT Rule:MF_01227}. FT BINDING 24 24 Allosteric inhibitor CTP; alternate. FT {ECO:0000255|HAMAP-Rule:MF_01227}. FT BINDING 24 24 UTP; alternate. {ECO:0000255|HAMAP- FT Rule:MF_01227}. FT BINDING 65 65 L-glutamine. {ECO:0000255|HAMAP- FT Rule:MF_01227}. FT BINDING 82 82 ATP. {ECO:0000255|HAMAP-Rule:MF_01227}. FT BINDING 234 234 Allosteric inhibitor CTP; alternate. FT {ECO:0000255|HAMAP-Rule:MF_01227}. FT BINDING 234 234 UTP; alternate. {ECO:0000255|HAMAP- FT Rule:MF_01227}. FT BINDING 363 363 L-glutamine; via carbonyl oxygen. FT {ECO:0000255|HAMAP-Rule:MF_01227}. FT BINDING 414 414 L-glutamine. {ECO:0000255|HAMAP- FT Rule:MF_01227}. FT BINDING 471 471 L-glutamine; via amide nitrogen. FT {ECO:0000255|HAMAP-Rule:MF_01227}. FT CONFLICT 395 397 CCV -> MLA (in Ref. 3; AAK13023). FT {ECO:0000305}. FT CONFLICT 403 403 D -> N (in Ref. 3; AAK13023). FT {ECO:0000305}. FT CONFLICT 407 409 WKD -> LKV (in Ref. 3; AAK13023). FT {ECO:0000305}. FT CONFLICT 421 428 HPVIDLMD -> PRFIRDLE (in Ref. 3; FT AAK13023). {ECO:0000305}. FT CONFLICT 432 435 NVTE -> DGHD (in Ref. 3; AAK13023). FT {ECO:0000305}. FT CONFLICT 444 444 A -> L (in Ref. 3; AAK13023). FT {ECO:0000305}. FT CONFLICT 457 458 KL -> NV (in Ref. 3; AAK13023). FT {ECO:0000305}. FT CONFLICT 461 461 S -> R (in Ref. 3; AAK13023). FT {ECO:0000305}. FT CONFLICT 465 465 S -> T (in Ref. 3; AAK13023). FT {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 //