PYRG_NITEU
ID PYRG_NITEU Reviewed; 564 AA.
AC O85347;
DT 19-OCT-2002, integrated into UniProtKB/Swiss-Prot.
DT 16-MAY-2003, sequence version 2.
DT 03-AUG-2022, entry version 130.
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=NE1045;
OS Nitrosomonas europaea (strain ATCC 19718 / CIP 103999 / KCTC 2705 / NBRC
OS 14298).
OC Bacteria; Proteobacteria; Betaproteobacteria; Nitrosomonadales;
OC Nitrosomonadaceae; Nitrosomonas.
OX NCBI_TaxID=228410;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 19718 / CIP 103999 / KCTC 2705 / NBRC 14298;
RX PubMed=12700255; DOI=10.1128/jb.185.9.2759-2773.2003;
RA Chain P., Lamerdin J.E., Larimer F.W., Regala W., Lao V., Land M.L.,
RA Hauser L., Hooper A.B., Klotz M.G., Norton J., Sayavedra-Soto L.A.,
RA Arciero D.M., Hommes N.G., Whittaker M.M., Arp D.J.;
RT "Complete genome sequence of the ammonia-oxidizing bacterium and obligate
RT chemolithoautotroph Nitrosomonas europaea.";
RL J. Bacteriol. 185:2759-2773(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 41-564.
RC STRAIN=ATCC 19718 / CIP 103999 / KCTC 2705 / NBRC 14298;
RX PubMed=9711852; DOI=10.1111/j.1574-6968.1998.tb13140.x;
RA Mahony T.J., Miller D.J.;
RT "Linkage of genes encoding enolase (eno) and CTP synthase (pyrG) in the
RT beta-subdivision proteobacterium Nitrosomonas europaea.";
RL FEMS Microbiol. Lett. 165:153-157(1998).
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; AL954747; CAD84956.1; -; Genomic_DNA.
DR EMBL; AF061753; AAC33441.1; -; Genomic_DNA.
DR RefSeq; WP_011111650.1; NC_004757.1.
DR AlphaFoldDB; O85347; -.
DR SMR; O85347; -.
DR STRING; 228410.NE1045; -.
DR MEROPS; C26.964; -.
DR EnsemblBacteria; CAD84956; CAD84956; NE1045.
DR KEGG; neu:NE1045; -.
DR eggNOG; COG0504; Bacteria.
DR HOGENOM; CLU_011675_5_0_4; -.
DR OMA; EFNNAYR; -.
DR OrthoDB; 783657at2; -.
DR PhylomeDB; O85347; -.
DR UniPathway; UPA00159; UER00277.
DR Proteomes; UP000001416; 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..564
FT /note="CTP synthase"
FT /id="PRO_0000138207"
FT DOMAIN 290..543
FT /note="Glutamine amidotransferase type-1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT REGION 1..265
FT /note="Amidoligase domain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT ACT_SITE 378
FT /note="Nucleophile; for glutamine hydrolysis"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT ACT_SITE 516
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT ACT_SITE 518
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 351
FT /ligand="L-glutamine"
FT /ligand_id="ChEBI:CHEBI:58359"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 379..382
FT /ligand="L-glutamine"
FT /ligand_id="ChEBI:CHEBI:58359"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 402
FT /ligand="L-glutamine"
FT /ligand_id="ChEBI:CHEBI:58359"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 469
FT /ligand="L-glutamine"
FT /ligand_id="ChEBI:CHEBI:58359"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT CONFLICT 105
FT /note="G -> A (in Ref. 2; AAC33441)"
FT /evidence="ECO:0000305"
FT CONFLICT 464
FT /note="E -> D (in Ref. 2; AAC33441)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 564 AA; 63079 MW; 5A432CF6D4DC2D58 CRC64;
MTKFVFVTGG VVSSLGKGIA AASLAALLET RGIRVTILKL DPYINVDPGT MNPFQHGEVF
VTDDGAETDL DLGHYERFIS TKMTRQNNFT TGQIYESVIR KERRGDYLGG TVQVIPHITD
EIKLFIRNGV SDAQVAIVEI GGTVGDIESL PFLEAIRQMS VQLPHHDTCF IHLTLLPYIS
SAGELKTKPT QHSVKELREI GIQPDVLLCR SDRPLPLEER RKIALFTNVR EESVISAIDV
DNIYKIPALL HEQMLDEIVC HRLDILARPA NLTVWKKLVH ALEHPEHEVS IALVGKYVDL
TESYKSLSEA LIHAGIHTRC KINIHYIDSE NIEQHGTGCL TNMDAILVPG GFGKRGVEGK
IMAISYARNH RIPYLGICLG MQLAVIEFSR NRLQLENAHS TEFDPDTPYP VLGLITEWRD
RCGRVEKRSA QTDLGGTMRL GGQECLLKPH TLAHKIYGAD KVIERHRHRY EVNAEFIPQL
EQAGMHISGL SAEGDLCEMI ELPQSEHPWF VACQFHPEFT STPRNGHPLF KSYIQAAISF
AGQSDRTKLH SRNVQESVTT DSSN
