ID C7R3T1_JONDD Unreviewed; 558 AA.
AC C7R3T1;
DT 13-OCT-2009, integrated into UniProtKB/TrEMBL.
DT 13-OCT-2009, sequence version 1.
DT 27-MAR-2024, entry version 87.
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 OrderedLocusNames=Jden_1132 {ECO:0000313|EMBL:ACV08788.1};
OS Jonesia denitrificans (strain ATCC 14870 / DSM 20603 / BCRC 15368 / CIP
OS 55.134 / JCM 11481 / NBRC 15587 / NCTC 10816 / Prevot 55134) (Listeria
OS denitrificans).
OC Bacteria; Actinomycetota; Actinomycetes; Micrococcales; Jonesiaceae;
OC Jonesia.
OX NCBI_TaxID=471856 {ECO:0000313|EMBL:ACV08788.1, ECO:0000313|Proteomes:UP000000628};
RN [1] {ECO:0000313|EMBL:ACV08788.1, ECO:0000313|Proteomes:UP000000628}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 14870 / DSM 20603 / BCRC 15368 / CIP 55.134 / JCM 11481 /
RC NBRC 15587 / NCTC 10816 / Prevot 55134
RC {ECO:0000313|Proteomes:UP000000628};
RX PubMed=21304666; DOI=10.4056/sigs.41646;
RA Pukall R., Gehrich-Schroter G., Lapidus A., Nolan M., Glavina Del Rio T.,
RA Lucas S., Chen F., Tice H., Pitluck S., Cheng J.F., Copeland A.,
RA Saunders E., Brettin T., Detter J.C., Bruce D., Goodwin L., Pati A.,
RA Ivanova N., Mavromatis K., Ovchinnikova G., Chen A., Palaniappan K.,
RA Land M., Hauser L., Chang Y.J., Jeffries C.D., Chain P., Goker M.,
RA Bristow J., Eisen J.A., Markowitz V., Hugenholtz P., Kyrpides N.C.,
RA Klenk H.P., Han C.;
RT "Complete genome sequence of Jonesia denitrificans type strain (Prevot
RT 55134).";
RL Stand. Genomic Sci. 1:262-269(2009).
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|ARBA:ARBA00000314, ECO:0000256|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:0000256|HAMAP-
CC 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:0000256|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: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|ARBA:ARBA00005171,
CC ECO:0000256|HAMAP-Rule:MF_01227}.
CC -!- SUBUNIT: Homotetramer. {ECO:0000256|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:0000256|HAMAP-Rule:MF_01227}.
CC -!- SIMILARITY: Belongs to the CTP synthase family.
CC {ECO:0000256|ARBA:ARBA00007533, ECO:0000256|HAMAP-Rule:MF_01227}.
CC -!- CAUTION: Lacks conserved residue(s) required for the propagation of
CC feature annotation. {ECO:0000256|HAMAP-Rule:MF_01227}.
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DR EMBL; CP001706; ACV08788.1; -; Genomic_DNA.
DR RefSeq; WP_015771416.1; NC_013174.1.
DR AlphaFoldDB; C7R3T1; -.
DR STRING; 471856.Jden_1132; -.
DR MEROPS; C26.964; -.
DR KEGG; jde:Jden_1132; -.
DR eggNOG; COG0504; Bacteria.
DR HOGENOM; CLU_011675_5_0_11; -.
DR UniPathway; UPA00159; UER00277.
DR Proteomes; UP000000628; 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-UniRule.
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 {ECO:0000256|ARBA:ARBA00022840, ECO:0000256|HAMAP-
KW Rule:MF_01227};
KW Glutamine amidotransferase {ECO:0000256|ARBA:ARBA00022962,
KW ECO:0000256|HAMAP-Rule:MF_01227};
KW Ligase {ECO:0000256|ARBA:ARBA00022598, ECO:0000256|HAMAP-Rule:MF_01227};
KW Magnesium {ECO:0000256|HAMAP-Rule:MF_01227};
KW Metal-binding {ECO:0000256|HAMAP-Rule:MF_01227};
KW Nucleotide-binding {ECO:0000256|ARBA:ARBA00022741, ECO:0000256|HAMAP-
KW Rule:MF_01227};
KW Pyrimidine biosynthesis {ECO:0000256|ARBA:ARBA00022975, ECO:0000256|HAMAP-
KW Rule:MF_01227}; Reference proteome {ECO:0000313|Proteomes:UP000000628}.
FT DOMAIN 21..284
FT /note="CTP synthase N-terminal"
FT /evidence="ECO:0000259|Pfam:PF06418"
FT DOMAIN 319..550
FT /note="Glutamine amidotransferase"
FT /evidence="ECO:0000259|Pfam:PF00117"
FT REGION 1..284
FT /note="Amidoligase domain"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227"
FT ACT_SITE 399
FT /note="Nucleophile"
FT /evidence="ECO:0000256|PROSITE-ProRule:PRU00605"
FT ACT_SITE 399
FT /note="Nucleophile; for glutamine hydrolysis"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227"
FT ACT_SITE 531
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227,
FT ECO:0000256|PROSITE-ProRule:PRU00605"
FT ACT_SITE 533
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227,
FT ECO:0000256|PROSITE-ProRule:PRU00605"
FT BINDING 31
FT /ligand="CTP"
FT /ligand_id="ChEBI:CHEBI:37563"
FT /ligand_note="allosteric inhibitor"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227"
FT BINDING 31
FT /ligand="UTP"
FT /ligand_id="ChEBI:CHEBI:46398"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227"
FT BINDING 32..37
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227"
FT BINDING 89
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227"
FT BINDING 89
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227"
FT BINDING 158
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227"
FT BINDING 165..167
FT /ligand="CTP"
FT /ligand_id="ChEBI:CHEBI:37563"
FT /ligand_note="allosteric inhibitor"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227"
FT BINDING 205..210
FT /ligand="CTP"
FT /ligand_id="ChEBI:CHEBI:37563"
FT /ligand_note="allosteric inhibitor"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227"
FT BINDING 205..210
FT /ligand="UTP"
FT /ligand_id="ChEBI:CHEBI:46398"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227"
FT BINDING 241
FT /ligand="CTP"
FT /ligand_id="ChEBI:CHEBI:37563"
FT /ligand_note="allosteric inhibitor"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227"
FT BINDING 241
FT /ligand="UTP"
FT /ligand_id="ChEBI:CHEBI:46398"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227"
FT BINDING 259
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227"
FT BINDING 372
FT /ligand="L-glutamine"
FT /ligand_id="ChEBI:CHEBI:58359"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227"
FT BINDING 400..403
FT /ligand="L-glutamine"
FT /ligand_id="ChEBI:CHEBI:58359"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227"
FT BINDING 423
FT /ligand="L-glutamine"
FT /ligand_id="ChEBI:CHEBI:58359"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227"
FT BINDING 484
FT /ligand="L-glutamine"
FT /ligand_id="ChEBI:CHEBI:58359"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227"
SQ SEQUENCE 558 AA; 60507 MW; 27784417824D883F CRC64;
MVNDANSALA PTSSTPAHVT RHIFVTGGVA SSLGKGLTAS SLGRVLRSRG VRVTMQKLDP
YLNVDPGTMN PFQHGEVFVT EDGAETDLDI GHYERFLDVN LDAVANVTTG QIYSSVIAKE
RRGEYLGDTV QVIPHITNAI KERMRAQASD DVDVIITEIG GTVGDIESQP FLESARQVRH
ELGRDNCFFV HVSLVPYIGP SGELKTKPTQ HSVAALRSIG IQPDAIVLRT DRDIPTSVKD
KIALMCDVDN EAVVTCQDAP SIYDIPRVIH AEGLDSYVVR RLGLDAGEVD WEQWDGLLRR
VHHPVHQVEV ALVGKYIDLP DAYLSVTEAL RAGGFAHDAK VAIRWVASDM CDTPEGAKDA
LAGVDAVLVP GGFGVRGIEG KIGALQWARE NAIPTLGICL GMQSMVMEYA RHVLGLEGAS
SSEFDPQTPH PVIATIKEQE EFVDGAGDLG GTMRLGAYPA VLREGSVLAQ TYGATEVSER
HRHRYEVNNA YREQLEAAGL HMSGTSPDGQ LVEFVELPRD VHPYYVSTQA HPEFKSRPTN
AHPLFSGLIA AALEQQHA
//
