PYRG_RICPR
ID PYRG_RICPR Reviewed; 586 AA.
AC Q9ZDF1;
DT 11-JUL-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 124.
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=RP378;
OS Rickettsia prowazekii (strain Madrid E).
OC Bacteria; Proteobacteria; Alphaproteobacteria; Rickettsiales;
OC Rickettsiaceae; Rickettsieae; Rickettsia; typhus group.
OX NCBI_TaxID=272947;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Madrid E;
RX PubMed=9823893; DOI=10.1038/24094;
RA Andersson S.G.E., Zomorodipour A., Andersson J.O., Sicheritz-Ponten T.,
RA Alsmark U.C.M., Podowski R.M., Naeslund A.K., Eriksson A.-S., Winkler H.H.,
RA Kurland C.G.;
RT "The genome sequence of Rickettsia prowazekii and the origin of
RT mitochondria.";
RL Nature 396:133-140(1998).
RN [2]
RP DOMAIN RPE1.
RX PubMed=11030655; DOI=10.1126/science.290.5490.347;
RA Ogata H., Audic S., Barbe V., Artiguenave F., Fournier P.-E., Raoult D.,
RA Claverie J.-M.;
RT "Selfish DNA in protein-coding genes of Rickettsia.";
RL Science 290:347-350(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; AJ235271; CAA14837.1; -; Genomic_DNA.
DR PIR; C71695; C71695.
DR RefSeq; NP_220761.1; NC_000963.1.
DR RefSeq; WP_004597537.1; NC_000963.1.
DR AlphaFoldDB; Q9ZDF1; -.
DR SMR; Q9ZDF1; -.
DR STRING; 272947.RP378; -.
DR EnsemblBacteria; CAA14837; CAA14837; CAA14837.
DR GeneID; 57569502; -.
DR KEGG; rpr:RP378; -.
DR PATRIC; fig|272947.5.peg.390; -.
DR eggNOG; COG0504; Bacteria.
DR HOGENOM; CLU_011675_5_0_5; -.
DR OMA; EFNNAYR; -.
DR UniPathway; UPA00159; UER00277.
DR Proteomes; UP000002480; 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; Reference proteome.
FT CHAIN 1..586
FT /note="CTP synthase"
FT /id="PRO_0000138217"
FT DOMAIN 290..582
FT /note="Glutamine amidotransferase type-1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT DOMAIN 429..473
FT /note="RPE1 insert"
FT REGION 1..265
FT /note="Amidoligase domain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT ACT_SITE 379
FT /note="Nucleophile; for glutamine hydrolysis"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT ACT_SITE 555
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT ACT_SITE 557
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 13
FT /ligand="CTP"
FT /ligand_id="ChEBI:CHEBI:37563"
FT /ligand_note="allosteric inhibitor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 13
FT /ligand="UTP"
FT /ligand_id="ChEBI:CHEBI:46398"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 14..19
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 71
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 71
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 139
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 146..148
FT /ligand="CTP"
FT /ligand_id="ChEBI:CHEBI:37563"
FT /ligand_note="allosteric inhibitor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 186..191
FT /ligand="CTP"
FT /ligand_id="ChEBI:CHEBI:37563"
FT /ligand_note="allosteric inhibitor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 186..191
FT /ligand="UTP"
FT /ligand_id="ChEBI:CHEBI:46398"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 222
FT /ligand="CTP"
FT /ligand_id="ChEBI:CHEBI:37563"
FT /ligand_note="allosteric inhibitor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 222
FT /ligand="UTP"
FT /ligand_id="ChEBI:CHEBI:46398"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 352
FT /ligand="L-glutamine"
FT /ligand_id="ChEBI:CHEBI:58359"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 380..383
FT /ligand="L-glutamine"
FT /ligand_id="ChEBI:CHEBI:58359"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 403
FT /ligand="L-glutamine"
FT /ligand_id="ChEBI:CHEBI:58359"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 510
FT /ligand="L-glutamine"
FT /ligand_id="ChEBI:CHEBI:58359"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
SQ SEQUENCE 586 AA; 66173 MW; FA14C0879F457A0A CRC64;
MVRFIFVTGG VVSSLGKGIT AASLAMLLQA KGFRVSVRKL DPYLNVDPGT MNPHEHGEVY
VTDDGAETDL DLGHYERFTG VTACKCDNIT TGAIYSKLLK DERLGNYTGI TVQVIPHVTN
IIKDFIMSNT NGFDFIICEI GGTVGDIEGL PFFEAIRQIG NKLKNANCLF IHLTLLPYVK
TARELKTKPT QHSVKELRAI GISPNILVCR AERNISKSAI DKIALFCNIK PEYVIPAIDQ
KNIYLVPIAY HNSGLENKVL NFFNINVVPS KLDKWYDIID KIKDSNSKVK IAIITKYHKT
QDAYKSVIEA LNHAGIYYKY KIDVLWINAE NLTEENINKK LLDINGILVP GGFGVRATQG
KMIAIKYART NNIPFFGICF GMQLATIEIA QNLIGIQDAV TEEFKIKGTK IIEKINKNCE
DATIKIKNAH ISKCTYSEAF ECDASTVYTN IHEDSNNLST DKLQIETNFR NMSDIEKTMR
LGAYPCNLVA NTIAANAYKS LEINERHRHR YKFNNEFQNI FEQHGVVFSG FSQNKQIVEI
IELPELRWFV GVQFHPEFKS KPFEAHPLFI QFIKATIEYN KSNEQQ
