ID   PYRG_VEREI              Reviewed;         554 AA.
AC   A1WL89;
DT   14-APR-2009, integrated into UniProtKB/Swiss-Prot.
DT   06-FEB-2007, sequence version 1.
DT   26-FEB-2020, entry version 86.
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=Veis_2653;
OS   Verminephrobacter eiseniae (strain EF01-2).
OC   Bacteria; Proteobacteria; Betaproteobacteria; Burkholderiales;
OC   Comamonadaceae; Verminephrobacter.
OX   NCBI_TaxID=391735;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=EF01-2;
RA   Copeland A., Lucas S., Lapidus A., Barry K., Detter J.C.,
RA   Glavina del Rio T., Dalin E., Tice H., Pitluck S., Chertkov O., Brettin T.,
RA   Bruce D., Han C., Tapia R., Gilna P., Schmutz J., Larimer F., Land M.,
RA   Hauser L., Kyrpides N., Kim E., Stahl D., Richardson P.;
RT   "Complete sequence of chromosome 1 of Verminephrobacter eiseniae EF01-2.";
RL   Submitted (DEC-2006) 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: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}.
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DR   EMBL; CP000542; ABM58396.1; -; Genomic_DNA.
DR   RefSeq; WP_011810395.1; NC_008786.1.
DR   SMR; A1WL89; -.
DR   STRING; 391735.Veis_2653; -.
DR   EnsemblBacteria; ABM58396; ABM58396; Veis_2653.
DR   KEGG; vei:Veis_2653; -.
DR   eggNOG; ENOG4105C8D; Bacteria.
DR   eggNOG; COG0504; LUCA.
DR   HOGENOM; CLU_011675_5_0_4; -.
DR   KO; K01937; -.
DR   OMA; EFNNAYR; -.
DR   OrthoDB; 783657at2; -.
DR   UniPathway; UPA00159; UER00277.
DR   Proteomes; UP000000374; 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-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; Glutamine amidotransferase; Ligase; Magnesium; Metal-binding;
KW   Nucleotide-binding; Pyrimidine biosynthesis; Reference proteome.
FT   CHAIN           1..554
FT                   /note="CTP synthase"
FT                   /id="PRO_1000139598"
FT   DOMAIN          295..548
FT                   /note="Glutamine amidotransferase type-1"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT   NP_BIND         14..19
FT                   /note="ATP"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT   NP_BIND         151..153
FT                   /note="Allosteric inhibitor CTP"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT   NP_BIND         191..196
FT                   /note="Allosteric inhibitor CTP; alternate"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT   NP_BIND         191..196
FT                   /note="UTP; alternate"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT   REGION          1..270
FT                   /note="Amidoligase domain"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT   REGION          385..388
FT                   /note="L-glutamine binding"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT   ACT_SITE        384
FT                   /note="Nucleophile; for glutamine hydrolysis"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT   ACT_SITE        521
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT   ACT_SITE        523
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT   METAL           71
FT                   /note="Magnesium"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT   METAL           144
FT                   /note="Magnesium"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT   BINDING         13
FT                   /note="Allosteric inhibitor CTP; alternate"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT   BINDING         13
FT                   /note="UTP; alternate"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT   BINDING         71
FT                   /note="ATP"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT   BINDING         227
FT                   /note="Allosteric inhibitor CTP; alternate"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT   BINDING         227
FT                   /note="UTP; alternate"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT   BINDING         357
FT                   /note="L-glutamine; via carbonyl oxygen"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT   BINDING         408
FT                   /note="L-glutamine"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT   BINDING         474
FT                   /note="L-glutamine; via amide nitrogen"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
SQ   SEQUENCE   554 AA;  61306 MW;  A1CD97835912DF86 CRC64;
     MTKFVFVTGG VVSSLGKGIA SASLAAILES RGLKVTLIKL DPYINVDPGT MSPFQHGEVF
     VTDDGAETDL DLGHYERFIE TRMNRANNFT TGKIYQSVLE KERRGDYLGK TVQVIPHVTN
     EIQEFIQRGA GMGTPVAVDV AIVEIGGTVG DIESLPFLEA VRQMSLRMGA NNSTFVHLTY
     LPWIATAGEL KTKPTQHTVQ KLREIGIQAD ALLCRADRRI PGEERAKISL FTNVPEWGVI
     SMWDVDIIYK VPRMLHEQGL DGLICDKLRL NTRPTNLQRW DDLVYATEHP QGAVTVAMVG
     KYVDLSDSYK SVNEALRHAG MRNHVRVQID HVDSETIDSA DAAARLARYD AILVPGGFGQ
     RGVEGKIATA RYAREHKLPY LGICLGMQVA TIEYARHVAG LANANSTEFD PATPHPVIAL
     ITEWQDADGS IQQRDQDSNL GGTMRLGAQS SDVLAGTLAH RIYGDVVTER HRHRYEANVN
     YLEPLRKAGL VIAALTQREQ LTEIVELPQS MHPWFIGVQF HPEFKSTPWN GHPLFNSFIA
     AAKARHQARH EGPA
//