ID A0A1L7FC56_9PSEU Unreviewed; 569 AA.
AC A0A1L7FC56;
DT 15-MAR-2017, integrated into UniProtKB/TrEMBL.
DT 15-MAR-2017, sequence version 1.
DT 13-SEP-2023, entry version 24.
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 ORFNames=UA75_22000 {ECO:0000313|EMBL:APU22389.1};
OS Actinoalloteichus sp. GBA129-24.
OC Bacteria; Actinomycetota; Actinomycetes; Pseudonocardiales;
OC Pseudonocardiaceae; Actinoalloteichus.
OX NCBI_TaxID=1612551 {ECO:0000313|EMBL:APU22389.1, ECO:0000313|Proteomes:UP000185506};
RN [1] {ECO:0000313|EMBL:APU22389.1, ECO:0000313|Proteomes:UP000185506}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=GBA129-24 {ECO:0000313|EMBL:APU22389.1,
RC ECO:0000313|Proteomes:UP000185506};
RA Ruckert C., Nouioui I., Willmese J., van Wezel G., Klenk H.-P.,
RA Kalinowski J., Zotchev S.B.;
RT "Complete genome sequence of Actinoalloteichus fjordicus DSM 46856
RT (=GBA129-24).";
RL Submitted (JUN-2016) 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: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; CP016077; APU22389.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A1L7FC56; -.
DR STRING; 1612551.UA75_22000; -.
DR KEGG; acti:UA75_22000; -.
DR UniPathway; UPA00159; UER00277.
DR Proteomes; UP000185506; 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}.
FT DOMAIN 8..276
FT /note="CTP synthase N-terminal"
FT /evidence="ECO:0000259|Pfam:PF06418"
FT DOMAIN 311..542
FT /note="Glutamine amidotransferase"
FT /evidence="ECO:0000259|Pfam:PF00117"
FT REGION 1..276
FT /note="Amidoligase domain"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227"
FT ACT_SITE 391
FT /note="Nucleophile"
FT /evidence="ECO:0000256|PROSITE-ProRule:PRU00605"
FT ACT_SITE 391
FT /note="Nucleophile; for glutamine hydrolysis"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227"
FT ACT_SITE 523
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227,
FT ECO:0000256|PROSITE-ProRule:PRU00605"
FT ACT_SITE 525
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227,
FT ECO:0000256|PROSITE-ProRule:PRU00605"
FT BINDING 18
FT /ligand="CTP"
FT /ligand_id="ChEBI:CHEBI:37563"
FT /ligand_note="allosteric inhibitor"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227"
FT BINDING 18
FT /ligand="UTP"
FT /ligand_id="ChEBI:CHEBI:46398"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227"
FT BINDING 19..24
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227"
FT BINDING 76
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227"
FT BINDING 76
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227"
FT BINDING 150
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227"
FT BINDING 157..159
FT /ligand="CTP"
FT /ligand_id="ChEBI:CHEBI:37563"
FT /ligand_note="allosteric inhibitor"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227"
FT BINDING 197..202
FT /ligand="CTP"
FT /ligand_id="ChEBI:CHEBI:37563"
FT /ligand_note="allosteric inhibitor"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227"
FT BINDING 197..202
FT /ligand="UTP"
FT /ligand_id="ChEBI:CHEBI:46398"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227"
FT BINDING 233
FT /ligand="CTP"
FT /ligand_id="ChEBI:CHEBI:37563"
FT /ligand_note="allosteric inhibitor"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227"
FT BINDING 233
FT /ligand="UTP"
FT /ligand_id="ChEBI:CHEBI:46398"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227"
FT BINDING 251
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227"
FT BINDING 364
FT /ligand="L-glutamine"
FT /ligand_id="ChEBI:CHEBI:58359"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227"
FT BINDING 392..395
FT /ligand="L-glutamine"
FT /ligand_id="ChEBI:CHEBI:58359"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227"
FT BINDING 415
FT /ligand="L-glutamine"
FT /ligand_id="ChEBI:CHEBI:58359"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227"
FT BINDING 476
FT /ligand="L-glutamine"
FT /ligand_id="ChEBI:CHEBI:58359"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227"
SQ SEQUENCE 569 AA; 61485 MW; 5888388B5D41F7EA CRC64;
MLQARTIKHV FVTGGVASSL GKGLTASSLG QLLTARGLRV TMQKLDPYLN VDPGTMNPFQ
HGEVFITEDG TETDLDVGHY ERFLDRDLSG RANVTTGQVY STVIAKERRG EYLGDTVQVI
PHITDEIKSR IRAMAEPDEN GITPDVVITE VGGTVGDIES LPFLEACRQV RHDLGRDNCF
FLHVSLVPYL APSGELKTKP TQHSVAALRN IGIQPDAIVC RSDREIPAAL KRKIALMCDV
DTDGVVAAPD ARSIYDIPRV VHAEGLDAFV VRRLGLPFRD VDWRVWGDLL DRVHQPAETV
RVALVGKYVD LPDAYLSVTE ALRAGGFAHH AKVEIVWVPS DQCDTDAGAS AALAGVDGIL
VPGGFGVRGI EGKVGAIRYA RTRGIPMLGL CLGLQCMVID VARDLAGLDG ANSAEFGEDC
VHPVISTMAD QEAVVAGERD MGGTMRLGAY PARLVAGTVT AKAYGATDVS ERHRHRYEVN
NAYRERLAEA GLVFSGLSPD DRLVEFVELP ADVHPFFVGT QAHPELKSRP TRPHPLFAAF
VRAAADYKAQ ERLPVELPEA APSKAGASR
//
