ID PYRG_METAC Reviewed; 534 AA. AC Q8TKW5; DT 19-OCT-2002, integrated into UniProtKB/Swiss-Prot. DT 01-JUN-2002, sequence version 1. DT 06-JUL-2016, 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=MA_3279; OS Methanosarcina acetivorans (strain ATCC 35395 / DSM 2834 / JCM 12185 / OS C2A). OC Archaea; Euryarchaeota; Methanomicrobia; Methanosarcinales; OC Methanosarcinaceae; Methanosarcina. OX NCBI_TaxID=188937; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=ATCC 35395 / DSM 2834 / JCM 12185 / C2A; RX PubMed=11932238; DOI=10.1101/gr.223902; RA Galagan J.E., Nusbaum C., Roy A., Endrizzi M.G., Macdonald P., RA FitzHugh W., Calvo S., Engels R., Smirnov S., Atnoor D., Brown A., RA Allen N., Naylor J., Stange-Thomann N., DeArellano K., Johnson R., RA Linton L., McEwan P., McKernan K., Talamas J., Tirrell A., Ye W., RA Zimmer A., Barber R.D., Cann I., Graham D.E., Grahame D.A., Guss A.M., RA Hedderich R., Ingram-Smith C., Kuettner H.C., Krzycki J.A., RA Leigh J.A., Li W., Liu J., Mukhopadhyay B., Reeve J.N., Smith K., RA Springer T.A., Umayam L.A., White O., White R.H., de Macario E.C., RA Ferry J.G., Jarrell K.F., Jing H., Macario A.J.L., Paulsen I.T., RA Pritchett M., Sowers K.R., Swanson R.V., Zinder S.H., Lander E., RA Metcalf W.W., Birren B.; RT "The genome of Methanosarcina acetivorans reveals extensive metabolic RT and physiological diversity."; RL Genome Res. 12:532-542(2002). 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 -!- ENZYME REGULATION: Allosterically activated by GTP, when glutamine CC is the substrate; GTP has no effect on the reaction when ammonia CC 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 -!- SIMILARITY: Contains 1 glutamine amidotransferase type-1 domain. 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; AE010299; AAM06649.1; -; Genomic_DNA. DR RefSeq; WP_011023212.1; NC_003552.1. DR ProteinModelPortal; Q8TKW5; -. DR SMR; Q8TKW5; 1-529. DR STRING; 188937.MA3279; -. DR EnsemblBacteria; AAM06649; AAM06649; MA_3279. DR GeneID; 1475172; -. DR KEGG; mac:MA_3279; -. DR eggNOG; arCOG00063; Archaea. DR eggNOG; COG0504; LUCA. DR InParanoid; Q8TKW5; -. DR KO; K01937; -. DR OMA; FDHNITT; -. DR PhylomeDB; Q8TKW5; -. DR BioCyc; MACE188937:GI2O-3314-MONOMER; -. DR UniPathway; UPA00159; UER00277. DR Proteomes; UP000002487; Chromosome. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0003883; F:CTP synthase activity; IEA:UniProtKB-HAMAP. DR GO; GO:0044210; P:'de novo' CTP biosynthetic process; IEA:UniProtKB-UniPathway. DR GO; GO:0006541; P:glutamine metabolic process; IEA:UniProtKB-HAMAP. DR Gene3D; 3.40.50.300; -; 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; 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 1 534 CTP synthase. FT /FTId=PRO_0000138259. FT DOMAIN 289 530 Glutamine amidotransferase type-1. FT {ECO:0000255|HAMAP-Rule:MF_01227}. FT NP_BIND 13 18 ATP. {ECO:0000255|HAMAP-Rule:MF_01227}. FT NP_BIND 147 149 Allosteric inhibitor CTP. FT {ECO:0000255|HAMAP-Rule:MF_01227}. FT NP_BIND 186 191 Allosteric inhibitor CTP; alternate. FT {ECO:0000255|HAMAP-Rule:MF_01227}. FT NP_BIND 186 191 UTP; alternate. {ECO:0000255|HAMAP- FT Rule:MF_01227}. FT REGION 1 265 Amidoligase domain. {ECO:0000255|HAMAP- FT Rule:MF_01227}. FT REGION 380 383 L-glutamine binding. {ECO:0000255|HAMAP- FT Rule:MF_01227}. FT ACT_SITE 379 379 Nucleophile; for glutamine hydrolysis. FT {ECO:0000255|HAMAP-Rule:MF_01227}. FT ACT_SITE 503 503 {ECO:0000255|HAMAP-Rule:MF_01227}. FT ACT_SITE 505 505 {ECO:0000255|HAMAP-Rule:MF_01227}. FT METAL 70 70 Magnesium. {ECO:0000255|HAMAP- FT Rule:MF_01227}. FT METAL 140 140 Magnesium. {ECO:0000255|HAMAP- FT Rule:MF_01227}. FT BINDING 12 12 Allosteric inhibitor CTP; alternate. FT {ECO:0000255|HAMAP-Rule:MF_01227}. FT BINDING 12 12 UTP; alternate. {ECO:0000255|HAMAP- FT Rule:MF_01227}. FT BINDING 53 53 L-glutamine. {ECO:0000255|HAMAP- FT Rule:MF_01227}. FT BINDING 70 70 ATP. {ECO:0000255|HAMAP-Rule:MF_01227}. FT BINDING 222 222 Allosteric inhibitor CTP; alternate. FT {ECO:0000255|HAMAP-Rule:MF_01227}. FT BINDING 222 222 UTP; alternate. {ECO:0000255|HAMAP- FT Rule:MF_01227}. FT BINDING 352 352 L-glutamine; via carbonyl oxygen. FT {ECO:0000255|HAMAP-Rule:MF_01227}. FT BINDING 403 403 L-glutamine. {ECO:0000255|HAMAP- FT Rule:MF_01227}. FT BINDING 460 460 L-glutamine; via amide nitrogen. FT {ECO:0000255|HAMAP-Rule:MF_01227}. SQ SEQUENCE 534 AA; 59730 MW; 2AC6AE3C578072DB CRC64; MKYIVVTGGV MSGLGKGITI ASIGRNLKNK GYKVTAIKID PYINIDAGTM SPYQHGEVFV LRDGGEVDLD LGNYERFLDT ELTRDHNLTT GKIYQEVIAK ERRGDYLGKT VQIIPHITNE IKSRIRKVAA RSGADVCLVE IGGTVGDIES MPFLEAVRQM HREEPSENIV FIHVTLVMED LQGEQKTKPS QHSVKELRAL GLSPEVIVTR SKTPLQESAK EKIALFCDVP QELVISAHDA ADIYEVPLEI EEQGLTTRLM KHLKLESSVE DNGWREMVSR MKSTTEEVKL AIVGKYTNLE DSYLSILEAV KHGGIDNGCK VEVNMVEAET LEEDPAEIEK LRQFDGILIP GGFGGRGTEG KMLAIKFARE NDVPFLGICL GMQLAVIEFA RNVVNLENAN STEFDEDTPY PVIDILPEQT GVADMGGTMR LGDYDAILKD GSLATKLYGT NYIVERHRHR YEVNPEFVDR LESFGIVFSG KNKNRMEIAE IPDKRFFFAS QFHPEFRSRP GRPSPPFKGL VRAMCKYNKE KEGQ //