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 07-APR-2021, entry version 109. 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=MA_3279; OS Methanosarcina acetivorans (strain ATCC 35395 / DSM 2834 / JCM 12185 / OS C2A). OC Archaea; Euryarchaeota; Stenosarchaea group; Methanomicrobia; OC Methanosarcinales; 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., FitzHugh W., RA Calvo S., Engels R., Smirnov S., Atnoor D., Brown A., Allen N., Naylor J., RA Stange-Thomann N., DeArellano K., Johnson R., Linton L., McEwan P., RA McKernan K., Talamas J., Tirrell A., Ye W., Zimmer A., Barber R.D., RA Cann I., Graham D.E., Grahame D.A., Guss A.M., Hedderich R., RA Ingram-Smith C., Kuettner H.C., Krzycki J.A., Leigh J.A., Li W., Liu J., RA Mukhopadhyay B., Reeve J.N., Smith K., Springer T.A., Umayam L.A., RA White O., White R.H., de Macario E.C., Ferry J.G., Jarrell K.F., Jing H., RA Macario A.J.L., Paulsen I.T., Pritchett M., Sowers K.R., Swanson R.V., RA Zinder S.H., Lander E., Metcalf W.W., Birren B.; RT "The genome of Methanosarcina acetivorans reveals extensive metabolic and RT 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: 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:0000255|HAMAP-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; AE010299; AAM06649.1; -; Genomic_DNA. DR RefSeq; WP_011023212.1; NC_003552.1. DR SMR; Q8TKW5; -. DR EnsemblBacteria; AAM06649; AAM06649; MA_3279. DR GeneID; 1475172; -. DR KEGG; mac:MA_3279; -. DR HOGENOM; CLU_011675_5_0_2; -. DR InParanoid; Q8TKW5; -. DR OMA; EFNNAYR; -. DR OrthoDB; 14061at2157; -. DR PhylomeDB; Q8TKW5; -. DR BioCyc; MACE188937:G1FZT-3487-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; IBA:GO_Central. DR GO; GO:0042802; F:identical protein binding; IBA:GO_Central. 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:0006241; P:CTP biosynthetic process; IBA:GO_Central. DR GO; GO:0006541; P:glutamine metabolic process; IEA:UniProtKB-KW. DR GO; GO:0019856; P:pyrimidine nucleobase biosynthetic process; IBA:GO_Central. DR CDD; cd03113; CTPS_N; 1. 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; Glutamine amidotransferase; Ligase; Magnesium; Metal-binding; KW Nucleotide-binding; Pyrimidine biosynthesis; Reference proteome. FT CHAIN 1..534 FT /note="CTP synthase" FT /id="PRO_0000138259" FT DOMAIN 289..530 FT /note="Glutamine amidotransferase type-1" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227" FT NP_BIND 13..18 FT /note="ATP" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227" FT NP_BIND 147..149 FT /note="CTP; allosteric inhibitor" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227" FT NP_BIND 186..191 FT /note="CTP; allosteric inhibitor; alternate" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227" FT NP_BIND 186..191 FT /note="UTP; alternate" 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 REGION 380..383 FT /note="L-glutamine binding" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227" FT ACT_SITE 379 FT /note="Nucleophile; for glutamine hydrolysis" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227" FT ACT_SITE 503 FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227" FT ACT_SITE 505 FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227" FT METAL 70 FT /note="Magnesium" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227" FT METAL 140 FT /note="Magnesium" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227" FT BINDING 12 FT /note="CTP; allosteric inhibitor; alternate" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227" FT BINDING 12 FT /note="UTP; alternate" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227" FT BINDING 53 FT /note="L-glutamine" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227" FT BINDING 70 FT /note="ATP" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227" FT BINDING 222 FT /note="CTP; allosteric inhibitor; alternate" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227" FT BINDING 222 FT /note="UTP; alternate" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227" FT BINDING 352 FT /note="L-glutamine; via carbonyl oxygen" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227" FT BINDING 403 FT /note="L-glutamine" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227" FT BINDING 460 FT /note="L-glutamine; via amide nitrogen" FT /evidence="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 //