ID A0A2A9BQ88_9BACI Unreviewed; 534 AA. AC A0A2A9BQ88; DT 20-DEC-2017, integrated into UniProtKB/TrEMBL. DT 20-DEC-2017, sequence version 1. DT 11-DEC-2019, entry version 9. 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 ORFNames=ATG71_1049 {ECO:0000313|EMBL:PFG04307.1}; OS Bacillus sp. es.034. OC Bacteria; Firmicutes; Bacilli; Bacillales; Bacillaceae; Bacillus. OX NCBI_TaxID=1761763 {ECO:0000313|EMBL:PFG04307.1, ECO:0000313|Proteomes:UP000225138}; RN [1] {ECO:0000313|EMBL:PFG04307.1, ECO:0000313|Proteomes:UP000225138} RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=es.034 {ECO:0000313|Proteomes:UP000225138}; RA Fredrickson J.; RT "Microbial Interactions in Extremophilic Mat Communities."; RL Submitted (OCT-2017) to the EMBL/GenBank/DDBJ databases. 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 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|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 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. {ECO:0000256|HAMAP- CC Rule:MF_01227, ECO:0000256|SAAS:SAAS00710794}. CC -!- CAUTION: Lacks conserved residue(s) required for the propagation of CC feature annotation. {ECO:0000256|HAMAP-Rule:MF_01227}. CC -!- CAUTION: The sequence shown here is derived from an EMBL/GenBank/DDBJ CC whole genome shotgun (WGS) entry which is preliminary data. CC {ECO:0000313|EMBL:PFG04307.1}. 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; PDIY01000001; PFG04307.1; -; Genomic_DNA. DR UniPathway; UPA00159; UER00277. DR Proteomes; UP000225138; Unassembled WGS sequence. 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 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, ECO:0000256|SAAS:SAAS00710762}; KW Magnesium {ECO:0000256|HAMAP-Rule:MF_01227, 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 292..534 FT /note="Glutamine amidotransferase type-1" FT /evidence="ECO:0000259|PROSITE:PS51273" FT NP_BIND 14..19 FT /note="ATP" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT NP_BIND 148..150 FT /note="Allosteric inhibitor CTP" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT NP_BIND 188..193 FT /note="Allosteric inhibitor CTP; alternate" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT NP_BIND 188..193 FT /note="UTP; alternate" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT REGION 1..267 FT /note="Amidoligase domain" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT REGION 382..385 FT /note="L-glutamine binding" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT ACT_SITE 381 FT /note="Nucleophile" FT /evidence="ECO:0000256|PROSITE-ProRule:PRU00605" FT ACT_SITE 381 FT /note="Nucleophile; for glutamine hydrolysis" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT ACT_SITE 507 FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227, FT ECO:0000256|PROSITE-ProRule:PRU00605" FT ACT_SITE 509 FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227, FT ECO:0000256|PROSITE-ProRule:PRU00605" FT METAL 71 FT /note="Magnesium" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT METAL 141 FT /note="Magnesium" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT BINDING 13 FT /note="Allosteric inhibitor CTP; alternate" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT BINDING 13 FT /note="UTP; alternate" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT BINDING 54 FT /note="L-glutamine" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT BINDING 71 FT /note="ATP" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT BINDING 224 FT /note="Allosteric inhibitor CTP; alternate" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT BINDING 224 FT /note="UTP; alternate" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT BINDING 242 FT /note="ATP" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT BINDING 354 FT /note="L-glutamine; via carbonyl oxygen" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT BINDING 405 FT /note="L-glutamine" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" FT BINDING 462 FT /note="L-glutamine; via amide nitrogen" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227" SQ SEQUENCE 534 AA; 59856 MW; C4E22254730EC7C2 CRC64; MTKYIFVTGG VVSSLGKGIT AASLGRLLKN RGVSVTIQKF DPYINVDPGT MSPYQHGEVF VTDDGAETDL DLGHYERFVD INLTKYSSVT TGKIYSTVLK KERRGDYLGG TVQVIPHITN EIKERVYRAG RETNSDVVIT EIGGTVGDIE SLPFLEAIRQ IKSDVGRDNV MYIHCTLIPY IKAAGEMKTK PTQHSVKELR SLGIQPNVIV VRTEMPMTQD MKDKIALFCD IDKHAVIEAM DADTLYSVPL ALQDQKLDEI TCQHLKLNCH EADMTEWNEL VDRVKNLSRK TRIALVGKYV ELQDAYISVV EALRHAGYHF DSDIEVRWLN SELVDNENVA EKLADVDGIL VPGGFGDRGV EGKIAATQYA RENKIPFLGI CLGMQLASVE YARNVLGMEG AHSAELNPET PYPVIDLLPE QKDIEDLGGT LRLGLYPCKL TKGSKAYAAY DGEVVYERHR HRFEFNNHYR EQMEKAGFIF SGTSPDGRLV EIIELSDHPW FVASQFHPEF TSRPTRPQPL FRDFVEASLA YGEK //