ID PYRG_METKA Reviewed; 535 AA.
AC Q8TYT7;
DT 19-OCT-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2002, sequence version 1.
DT 27-MAR-2024, entry version 114.
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=MK0205;
OS Methanopyrus kandleri (strain AV19 / DSM 6324 / JCM 9639 / NBRC 100938).
OC Archaea; Euryarchaeota; Methanomada group; Methanopyri; Methanopyrales;
OC Methanopyraceae; Methanopyrus.
OX NCBI_TaxID=190192;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=AV19 / DSM 6324 / JCM 9639 / NBRC 100938;
RX PubMed=11930014; DOI=10.1073/pnas.032671499;
RA Slesarev A.I., Mezhevaya K.V., Makarova K.S., Polushin N.N.,
RA Shcherbinina O.V., Shakhova V.V., Belova G.I., Aravind L., Natale D.A.,
RA Rogozin I.B., Tatusov R.L., Wolf Y.I., Stetter K.O., Malykh A.G.,
RA Koonin E.V., Kozyavkin S.A.;
RT "The complete genome of hyperthermophile Methanopyrus kandleri AV19 and
RT monophyly of archaeal methanogens.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:4644-4649(2002).
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; AE009439; AAM01422.1; -; Genomic_DNA.
DR AlphaFoldDB; Q8TYT7; -.
DR SMR; Q8TYT7; -.
DR STRING; 190192.MK0205; -.
DR PaxDb; 190192-MK0205; -.
DR EnsemblBacteria; AAM01422; AAM01422; MK0205.
DR KEGG; mka:MK0205; -.
DR PATRIC; fig|190192.8.peg.206; -.
DR HOGENOM; CLU_011675_5_0_2; -.
DR InParanoid; Q8TYT7; -.
DR UniPathway; UPA00159; UER00277.
DR Proteomes; UP000001826; 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; Reference proteome.
FT CHAIN 1..535
FT /note="CTP synthase"
FT /id="PRO_0000138261"
FT DOMAIN 291..535
FT /note="Glutamine amidotransferase type-1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT REGION 1..266
FT /note="Amidoligase domain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT ACT_SITE 382
FT /note="Nucleophile; for glutamine hydrolysis"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT ACT_SITE 508
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT ACT_SITE 510
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 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 187..192
FT /ligand="CTP"
FT /ligand_id="ChEBI:CHEBI:37563"
FT /ligand_note="allosteric inhibitor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 187..192
FT /ligand="UTP"
FT /ligand_id="ChEBI:CHEBI:46398"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 223
FT /ligand="CTP"
FT /ligand_id="ChEBI:CHEBI:37563"
FT /ligand_note="allosteric inhibitor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 223
FT /ligand="UTP"
FT /ligand_id="ChEBI:CHEBI:46398"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 355
FT /ligand="L-glutamine"
FT /ligand_id="ChEBI:CHEBI:58359"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 383..386
FT /ligand="L-glutamine"
FT /ligand_id="ChEBI:CHEBI:58359"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 406
FT /ligand="L-glutamine"
FT /ligand_id="ChEBI:CHEBI:58359"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 464
FT /ligand="L-glutamine"
FT /ligand_id="ChEBI:CHEBI:58359"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
SQ SEQUENCE 535 AA; 59460 MW; 4C2816FC0DF4620A CRC64;
MKFVVITGGV VSGIGKGITT ASIGRILRAR ELEVTAVKID PYINVDAGTM NPFQHGEVFV
TEDGVETDLD LGHYERFMDV TLSGAHNITT GKIYQRVIEK ERRGDYLGET VQVIPHITDE
IKSWIREVGK ASGADVVLVE IGGTVGDIEG MPFYEAVRQL QLEEGRENVM FVHLTYVPYL
EHVHELKTKP TQHSVKELRS LGIQPDAIVC RCERPLDDGV KRKIALHTNV PREAVIDAHD
VDLVYKVPLL LERQGFGDYI CERLGLDADE PDYSDWLDFV TRIEEADDEI RIAVVGKYVD
LPDAYISIRE ALVHAGAHVG VGVDVAWVDS EALEAGDSEA WEEVKDADGV LVPGGFGKRG
VEGKIEAVRY ARENDVPFLG ICLGFQLVVV EYARSVLGLE DAHSTEFNPD TDHPVVDLLP
EQRGVKRKGG TMRLGAEPVV LEEGSLLRRL YDDREIVLER HRHRYEVNPS YVRELEDHGL
RFSGHSPDGR MEALELPDHP YFVGTQFHPE FKSRPGDPSP PFVGLIKAAA GQGPD
//
