PYRG_THEVO
ID PYRG_THEVO Reviewed; 540 AA.
AC Q97CR8;
DT 19-OCT-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2001, sequence version 1.
DT 03-AUG-2022, entry version 116.
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=TV0033;
GN ORFNames=TVG0036820;
OS Thermoplasma volcanium (strain ATCC 51530 / DSM 4299 / JCM 9571 / NBRC
OS 15438 / GSS1).
OC Archaea; Candidatus Thermoplasmatota; Thermoplasmata; Thermoplasmatales;
OC Thermoplasmataceae; Thermoplasma.
OX NCBI_TaxID=273116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 51530 / DSM 4299 / JCM 9571 / NBRC 15438 / GSS1;
RX PubMed=11121031; DOI=10.1073/pnas.97.26.14257;
RA Kawashima T., Amano N., Koike H., Makino S., Higuchi S., Kawashima-Ohya Y.,
RA Watanabe K., Yamazaki M., Kanehori K., Kawamoto T., Nunoshiba T.,
RA Yamamoto Y., Aramaki H., Makino K., Suzuki M.;
RT "Archaeal adaptation to higher temperatures revealed by genomic sequence of
RT Thermoplasma volcanium.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:14257-14262(2000).
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; BA000011; BAB59175.1; -; Genomic_DNA.
DR RefSeq; WP_010916290.1; NC_002689.2.
DR AlphaFoldDB; Q97CR8; -.
DR SMR; Q97CR8; -.
DR STRING; 273116.14324247; -.
DR EnsemblBacteria; BAB59175; BAB59175; BAB59175.
DR GeneID; 1441519; -.
DR KEGG; tvo:TVG0036820; -.
DR eggNOG; arCOG00063; Archaea.
DR HOGENOM; CLU_011675_5_0_2; -.
DR OMA; EFNNAYR; -.
DR OrthoDB; 14061at2157; -.
DR PhylomeDB; Q97CR8; -.
DR UniPathway; UPA00159; UER00277.
DR Proteomes; UP000001017; 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; 3.40.50.300; -; 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.
FT CHAIN 1..540
FT /note="CTP synthase"
FT /id="PRO_0000138273"
FT DOMAIN 294..527
FT /note="Glutamine amidotransferase type-1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT REGION 1..264
FT /note="Amidoligase domain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT ACT_SITE 374
FT /note="Nucleophile; for glutamine hydrolysis"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT ACT_SITE 500
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT ACT_SITE 502
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 12
FT /ligand="CTP"
FT /ligand_id="ChEBI:CHEBI:37563"
FT /ligand_note="allosteric inhibitor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 12
FT /ligand="UTP"
FT /ligand_id="ChEBI:CHEBI:46398"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 13..18
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 53
FT /ligand="L-glutamine"
FT /ligand_id="ChEBI:CHEBI:58359"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 70
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 70
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 140
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 147..149
FT /ligand="CTP"
FT /ligand_id="ChEBI:CHEBI:37563"
FT /ligand_note="allosteric inhibitor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 185..190
FT /ligand="CTP"
FT /ligand_id="ChEBI:CHEBI:37563"
FT /ligand_note="allosteric inhibitor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 185..190
FT /ligand="UTP"
FT /ligand_id="ChEBI:CHEBI:46398"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 221
FT /ligand="CTP"
FT /ligand_id="ChEBI:CHEBI:37563"
FT /ligand_note="allosteric inhibitor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 221
FT /ligand="UTP"
FT /ligand_id="ChEBI:CHEBI:46398"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 347
FT /ligand="L-glutamine"
FT /ligand_id="ChEBI:CHEBI:58359"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 375..378
FT /ligand="L-glutamine"
FT /ligand_id="ChEBI:CHEBI:58359"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 398
FT /ligand="L-glutamine"
FT /ligand_id="ChEBI:CHEBI:58359"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 455
FT /ligand="L-glutamine"
FT /ligand_id="ChEBI:CHEBI:58359"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
SQ SEQUENCE 540 AA; 60572 MW; 4E0C7B2382FF0E42 CRC64;
MQYIVVTGGV ISGLGKGTIT SSIGHILKDS GFKVSSVKID PYINYDAGTM NPYQHGEVFV
LDDGSEVDLD LGNYERFMDI NLSWKNNITT GKVYLEVIEK ERHGDYLGKT VQIIPHITDE
IKRRIRDVAT SSKADFVLIE VGGTVGDIES MPFLEAVRQL KREENNVIFA HVTLVPEIGP
TEEQKTKPTQ HSVKALREIG IQPDIIFARS KNRLLEETKK RISLFTDVPE GGIISVYDVE
NVYLLPEVMV NEGFISYLSK LSGKEIKYRD SWKAYTENIK HPKDRVKIAI VGKYVDLHDA
YISHKEAFSH VTGNTGIAVD IKWLDSEKVK DDQSMLSDVD AILIPGGFGY RGVEGKIAAT
RFALENHIPF LGICLGFQVA VIEIARDIIG LQNANSTEFD PATKYPVIDI LPEQKGIKDL
GGTMRLGSKK VLIKDGTLAK RIYGTDTIYE RHRHRYEVNP NYISIIEKAG FVFSGTDEDG
IRMEILEKKG DESFIATQYH SEFKSRPLNP SRVHLHLVQQ ALIYKKNKDI GEAVKLRSSV
