ID H6RWF7_BLASD Unreviewed; 593 AA.
AC H6RWF7;
DT 18-APR-2012, integrated into UniProtKB/TrEMBL.
DT 18-APR-2012, sequence version 1.
DT 24-JAN-2024, entry version 69.
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 ECO:0000313|EMBL:CCG03372.1};
GN OrderedLocusNames=BLASA_2491 {ECO:0000313|EMBL:CCG03372.1};
OS Blastococcus saxobsidens (strain DD2).
OC Bacteria; Actinomycetota; Actinomycetes; Geodermatophilales;
OC Geodermatophilaceae; Blastococcus.
OX NCBI_TaxID=1146883 {ECO:0000313|EMBL:CCG03372.1, ECO:0000313|Proteomes:UP000007517};
RN [1] {ECO:0000313|EMBL:CCG03372.1, ECO:0000313|Proteomes:UP000007517}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=DD2 {ECO:0000313|EMBL:CCG03372.1,
RC ECO:0000313|Proteomes:UP000007517};
RX PubMed=22535935; DOI=10.1128/JB.00320-12;
RA Chouaia B., Crotti E., Brusetti L., Daffonchio D., Essoussi I., Nouioui I.,
RA Sbissi I., Ghodhbane-Gtari F., Gtari M., Vacherie B., Barbe V., Medigue C.,
RA Gury J., Pujic P., Normand P.;
RT "Genome Sequence of Blastococcus saxobsidens DD2, a Stone-Inhabiting
RT Bacterium.";
RL J. Bacteriol. 194:2752-2753(2012).
RN [2] {ECO:0000313|Proteomes:UP000007517}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=DD2 {ECO:0000313|Proteomes:UP000007517};
RA Genoscope.;
RT "Complete genome sequence of Blastococcus saxobsidens strain DD2.";
RL Submitted (FEB-2012) 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; FO117623; CCG03372.1; -; Genomic_DNA.
DR AlphaFoldDB; H6RWF7; -.
DR STRING; 1146883.BLASA_2491; -.
DR MEROPS; C26.964; -.
DR KEGG; bsd:BLASA_2491; -.
DR eggNOG; COG0504; Bacteria.
DR HOGENOM; CLU_011675_5_0_11; -.
DR OMA; EFNNAYR; -.
DR OrthoDB; 9801107at2; -.
DR UniPathway; UPA00159; UER00277.
DR Proteomes; UP000007517; 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:UP000007517}.
FT DOMAIN 39..304
FT /note="CTP synthase N-terminal"
FT /evidence="ECO:0000259|Pfam:PF06418"
FT DOMAIN 339..570
FT /note="Glutamine amidotransferase"
FT /evidence="ECO:0000259|Pfam:PF00117"
FT REGION 1..304
FT /note="Amidoligase domain"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227"
FT ACT_SITE 419
FT /note="Nucleophile"
FT /evidence="ECO:0000256|PROSITE-ProRule:PRU00605"
FT ACT_SITE 419
FT /note="Nucleophile; for glutamine hydrolysis"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227"
FT ACT_SITE 551
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227,
FT ECO:0000256|PROSITE-ProRule:PRU00605"
FT ACT_SITE 553
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227,
FT ECO:0000256|PROSITE-ProRule:PRU00605"
FT BINDING 49
FT /ligand="CTP"
FT /ligand_id="ChEBI:CHEBI:37563"
FT /ligand_note="allosteric inhibitor"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227"
FT BINDING 49
FT /ligand="UTP"
FT /ligand_id="ChEBI:CHEBI:46398"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227"
FT BINDING 50..55
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227"
FT BINDING 107
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227"
FT BINDING 107
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227"
FT BINDING 178
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227"
FT BINDING 185..187
FT /ligand="CTP"
FT /ligand_id="ChEBI:CHEBI:37563"
FT /ligand_note="allosteric inhibitor"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227"
FT BINDING 225..230
FT /ligand="CTP"
FT /ligand_id="ChEBI:CHEBI:37563"
FT /ligand_note="allosteric inhibitor"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227"
FT BINDING 225..230
FT /ligand="UTP"
FT /ligand_id="ChEBI:CHEBI:46398"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227"
FT BINDING 261
FT /ligand="CTP"
FT /ligand_id="ChEBI:CHEBI:37563"
FT /ligand_note="allosteric inhibitor"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227"
FT BINDING 261
FT /ligand="UTP"
FT /ligand_id="ChEBI:CHEBI:46398"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227"
FT BINDING 279
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227"
FT BINDING 392
FT /ligand="L-glutamine"
FT /ligand_id="ChEBI:CHEBI:58359"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227"
FT BINDING 420..423
FT /ligand="L-glutamine"
FT /ligand_id="ChEBI:CHEBI:58359"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227"
FT BINDING 443
FT /ligand="L-glutamine"
FT /ligand_id="ChEBI:CHEBI:58359"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227"
FT BINDING 504
FT /ligand="L-glutamine"
FT /ligand_id="ChEBI:CHEBI:58359"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01227"
SQ SEQUENCE 593 AA; 63905 MW; D301F9F61370D498 CRC64;
MALPTPTRLT APAVLRSSPV DRPSGMRDHG LLHNSQPTKF VFVTGGVVSS LGKGLTASSL
GALLSSRGLR VTMQKLDPYL NVDPGTMNPF QHGEVFVTED GAETDLDVGH YERFLDIDLS
GRANVTTGQV YSDVIAKERR GEYLGDTVQV IPHITNEIKA RILDGADSAE RVDVVITEIG
GTVGDIESLP FLEAARQVRH EIGRDNCFFL HISLVPYIAP SGELKTKPTQ HSVAALRSIG
IQPDALVCRS DREINEGLKR KISLMCDTDP EGVISCPDAP SIYDIPKVLH REGLDAYVVR
RLGLPFRDVD WTVWGDLLAR VHDPKQTVTI ALVGKYIDLP DAYLSVTEAL RAGGFAHRSR
VQIRWVPSDD CETPEGAEKT LAGVDGVCIP GGFGVRGIEG KLGAIRHARV NGIPTLGLCL
GLQCMVIETA RNLAGIDGAN STEFDPETPA AVISTMATQL DVVAGRGDMG GTMRLGSYPA
HLQKGSVAAA AYGATEITER HRHRYEVANA YRDRLSEAGL VFSGTSPDGT LVEFAELPRG
THPFFVGTQA HPELKSRPTR PHPLFAAFVQ AAVDYQEAAR LPVPVDEGQQ VGV
//