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 27-MAR-2024, entry version 112.
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; Fibrobacterota; Fibrobacteria; 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., Bruce D.,
RA Goodwin L., Pitluck S., Chertkov O., Detter J.C., Han C., Tapia R.,
RA Larimer F., Land M., Hauser L., Kyrpides N., Mikhailova N., Weimer P.J.,
RA Stevenson D.M., Boyum J., Brumm P.I., Mead D.;
RT "Complete sequence of Fibrobacter succinogenes subsp. succinogenes 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 S85.";
RL Submitted (AUG-2010) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 388-520.
RX PubMed=11535801; DOI=10.1099/00221287-147-9-2611;
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 Fibrobacter
RT diverged at a similar time to Chlamydia and the Cytophaga-Flavobacterium-
RT 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:
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 -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + L-glutamine = L-glutamate + NH4(+);
CC Xref=Rhea:RHEA:15889, ChEBI:CHEBI:15377, ChEBI:CHEBI:28938,
CC ChEBI:CHEBI:29985, ChEBI:CHEBI:58359; Evidence={ECO:0000255|HAMAP-
CC Rule:MF_01227};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + NH4(+) + UTP = ADP + CTP + 2 H(+) + phosphate;
CC Xref=Rhea:RHEA:16597, ChEBI:CHEBI:15378, ChEBI:CHEBI:28938,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:37563, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:46398, ChEBI:CHEBI:456216; Evidence={ECO:0000255|HAMAP-
CC 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; 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 AlphaFoldDB; Q939R0; -.
DR SMR; Q939R0; -.
DR STRING; 59374.FSU_2325; -.
DR MEROPS; C26.964; -.
DR GeneID; 34756163; -.
DR KEGG; fsc:FSU_2325; -.
DR KEGG; fsu:Fisuc_1822; -.
DR PATRIC; fig|59374.8.peg.2235; -.
DR eggNOG; COG0504; Bacteria.
DR HOGENOM; CLU_011675_5_0_0; -.
DR OrthoDB; 9801107at2; -.
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-UniRule.
DR GO; GO:0004359; F:glutaminase activity; IEA:RHEA.
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; cd03113; CTPS_N; 1.
DR CDD; cd01746; GATase1_CTP_Synthase; 1.
DR Gene3D; 3.40.50.880; -; 1.
DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 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 NCBIfam; TIGR00337; PyrG; 1.
DR PANTHER; PTHR11550; CTP SYNTHASE; 1.
DR PANTHER; PTHR11550:SF0; CTP SYNTHASE-RELATED; 1.
DR Pfam; PF06418; CTP_synth_N; 1.
DR Pfam; PF00117; GATase; 1.
DR SUPFAM; SSF52317; Class I glutamine amidotransferase-like; 1.
DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 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.
FT CHAIN 1..563
FT /note="CTP synthase"
FT /id="PRO_0000138186"
FT DOMAIN 303..545
FT /note="Glutamine amidotransferase type-1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT REGION 1..278
FT /note="Amidoligase domain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT REGION 542..563
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 390
FT /note="Nucleophile; for glutamine hydrolysis"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT ACT_SITE 518
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT ACT_SITE 520
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 24
FT /ligand="CTP"
FT /ligand_id="ChEBI:CHEBI:37563"
FT /ligand_note="allosteric inhibitor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 24
FT /ligand="UTP"
FT /ligand_id="ChEBI:CHEBI:46398"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 25..30
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 65
FT /ligand="L-glutamine"
FT /ligand_id="ChEBI:CHEBI:58359"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 82
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 82
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 151
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 158..160
FT /ligand="CTP"
FT /ligand_id="ChEBI:CHEBI:37563"
FT /ligand_note="allosteric inhibitor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 198..203
FT /ligand="CTP"
FT /ligand_id="ChEBI:CHEBI:37563"
FT /ligand_note="allosteric inhibitor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 198..203
FT /ligand="UTP"
FT /ligand_id="ChEBI:CHEBI:46398"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 234
FT /ligand="CTP"
FT /ligand_id="ChEBI:CHEBI:37563"
FT /ligand_note="allosteric inhibitor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 234
FT /ligand="UTP"
FT /ligand_id="ChEBI:CHEBI:46398"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 250..252
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 363
FT /ligand="L-glutamine"
FT /ligand_id="ChEBI:CHEBI:58359"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 391..394
FT /ligand="L-glutamine"
FT /ligand_id="ChEBI:CHEBI:58359"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 414
FT /ligand="L-glutamine"
FT /ligand_id="ChEBI:CHEBI:58359"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 471
FT /ligand="L-glutamine"
FT /ligand_id="ChEBI:CHEBI:58359"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT CONFLICT 395..397
FT /note="CCV -> MLA (in Ref. 3; AAK13023)"
FT /evidence="ECO:0000305"
FT CONFLICT 403
FT /note="D -> N (in Ref. 3; AAK13023)"
FT /evidence="ECO:0000305"
FT CONFLICT 407..409
FT /note="WKD -> LKV (in Ref. 3; AAK13023)"
FT /evidence="ECO:0000305"
FT CONFLICT 421..428
FT /note="HPVIDLMD -> PRFIRDLE (in Ref. 3; AAK13023)"
FT /evidence="ECO:0000305"
FT CONFLICT 432..435
FT /note="NVTE -> DGHD (in Ref. 3; AAK13023)"
FT /evidence="ECO:0000305"
FT CONFLICT 444
FT /note="A -> L (in Ref. 3; AAK13023)"
FT /evidence="ECO:0000305"
FT CONFLICT 457..458
FT /note="KL -> NV (in Ref. 3; AAK13023)"
FT /evidence="ECO:0000305"
FT CONFLICT 461
FT /note="S -> R (in Ref. 3; AAK13023)"
FT /evidence="ECO:0000305"
FT CONFLICT 465
FT /note="S -> T (in Ref. 3; AAK13023)"
FT /evidence="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
//
