PYRG_HALHT
ID PYRG_HALHT Reviewed; 553 AA.
AC G0HV10;
DT 07-OCT-2020, integrated into UniProtKB/Swiss-Prot.
DT 07-OCT-2020, sequence version 2.
DT 03-AUG-2022, entry version 57.
DE RecName: Full=CTP synthase {ECO:0000255|HAMAP-Rule:MF_01227, ECO:0000303|PubMed:32507415};
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, ECO:0000303|PubMed:32507415};
DE AltName: Full=UTP--ammonia ligase {ECO:0000255|HAMAP-Rule:MF_01227};
GN Name=pyrG {ECO:0000255|HAMAP-Rule:MF_01227}; OrderedLocusNames=HAH_0694;
OS Haloarcula hispanica (strain ATCC 33960 / DSM 4426 / JCM 8911 / NBRC 102182
OS / NCIMB 2187 / VKM B-1755).
OC Archaea; Euryarchaeota; Stenosarchaea group; Halobacteria; Halobacteriales;
OC Haloarculaceae; Haloarcula.
OX NCBI_TaxID=634497;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 33960 / DSM 4426 / JCM 8911 / NBRC 102182 / NCIMB 2187 / VKM
RC B-1755;
RX PubMed=21994921; DOI=10.1128/jb.05953-11;
RA Liu H., Wu Z., Li M., Zhang F., Zheng H., Han J., Liu J., Zhou J., Wang S.,
RA Xiang H.;
RT "Complete genome sequence of Haloarcula hispanica, a model haloarchaeon for
RT studying genetics, metabolism, and virus-host interaction.";
RL J. Bacteriol. 193:6086-6087(2011).
RN [2]
RP ACTIVITY REGULATION, AND SUBCELLULAR LOCATION.
RC STRAIN=ATCC 33960 / DSM 4426 / JCM 8911 / NBRC 102182 / NCIMB 2187 / VKM
RC B-1755;
RX PubMed=32507415; DOI=10.1016/j.jgg.2020.03.004;
RA Zhou S., Xiang H., Liu J.L.;
RT "CTP synthase forms cytoophidia in archaea.";
RL J. Genet. Genomics 47:213-223(2020).
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 (By similarity).
CC Inhibited by 6-diazo-5-oxo-l-norleucine (DON) (PubMed:32507415).
CC {ECO:0000255|HAMAP-Rule:MF_01227, ECO:0000269|PubMed:32507415}.
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 -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:32507415}.
CC Note=Localizes to the cytoophidium, a short subcellular filamentary
CC structure where CTP synthase is compartmentalized. Only a few cells
CC form cytoophidia under standard growth conditions, they are observed in
CC late log phase. Stress conditions such as treatment with 50 uM 6-diazo-
CC 5-oxo-l-norleucine (DON, an inhibitor) or growth at low salt (1.5 M
CC instead of the usual 3.4 M) also induces their appearance. In all these
CC conditions cells are barely growing. {ECO:0000269|PubMed:32507415}.
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}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AEM56317.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305|PubMed:32507415};
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DR EMBL; CP002921; AEM56317.1; ALT_INIT; Genomic_DNA.
DR RefSeq; WP_044951697.1; NC_015948.1.
DR AlphaFoldDB; G0HV10; -.
DR SMR; G0HV10; -.
DR STRING; 634497.HAH_0694; -.
DR MEROPS; C26.964; -.
DR EnsemblBacteria; AEM56317; AEM56317; HAH_0694.
DR GeneID; 25156360; -.
DR KEGG; hhi:HAH_0694; -.
DR eggNOG; arCOG00063; Archaea.
DR HOGENOM; CLU_011675_5_0_2; -.
DR UniPathway; UPA00159; UER00277.
DR Proteomes; UP000005629; Chromosome I.
DR GO; GO:0097268; C:cytoophidium; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
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; Cytoplasm; Glutamine amidotransferase; Ligase; Magnesium;
KW Metal-binding; Nucleotide-binding; Pyrimidine biosynthesis.
FT CHAIN 1..553
FT /note="CTP synthase"
FT /id="PRO_0000451061"
FT DOMAIN 307..544
FT /note="Glutamine amidotransferase type-1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227,
FT ECO:0000255|PROSITE-ProRule:PRU00605"
FT REGION 1..277
FT /note="Amidoligase domain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT ACT_SITE 391
FT /note="Nucleophile; for glutamine hydrolysis"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT ACT_SITE 517
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227,
FT ECO:0000255|PROSITE-ProRule:PRU00605"
FT ACT_SITE 519
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227,
FT ECO:0000255|PROSITE-ProRule:PRU00605"
FT BINDING 26
FT /ligand="CTP"
FT /ligand_id="ChEBI:CHEBI:37563"
FT /ligand_note="allosteric inhibitor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 26
FT /ligand="UTP"
FT /ligand_id="ChEBI:CHEBI:46398"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 27..32
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 84
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 84
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 152
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 159..161
FT /ligand="CTP"
FT /ligand_id="ChEBI:CHEBI:37563"
FT /ligand_note="allosteric inhibitor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 198..203
FT /ligand="CTP"
FT /ligand_id="ChEBI:CHEBI:37563"
FT /ligand_note="allosteric inhibitor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 198..203
FT /ligand="UTP"
FT /ligand_id="ChEBI:CHEBI:46398"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 234
FT /ligand="CTP"
FT /ligand_id="ChEBI:CHEBI:37563"
FT /ligand_note="allosteric inhibitor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 234
FT /ligand="UTP"
FT /ligand_id="ChEBI:CHEBI:46398"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 252
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 364
FT /ligand="L-glutamine"
FT /ligand_id="ChEBI:CHEBI:58359"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 392..395
FT /ligand="L-glutamine"
FT /ligand_id="ChEBI:CHEBI:58359"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 415
FT /ligand="L-glutamine"
FT /ligand_id="ChEBI:CHEBI:58359"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 472
FT /ligand="L-glutamine"
FT /ligand_id="ChEBI:CHEBI:58359"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
SQ SEQUENCE 553 AA; 61893 MW; F8080C01F8A46379 CRC64;
MPTEPETDYD PELGRKFIFV TGGVMSGLGK GITAASTGRL LKNAGFDVTA VKIDPYLNVD
AGTMNPFQHG EVYVLKDGGE VDLDLGNYER FLDIDMTFDH NVTTGKTYQH VIEKERSGDY
LGRTVQIIPH ITDDIKRRIR EAAEGNDVCI IEVGGTVGDI EGMPYLEALR QFAHEEDEDD
ILFTHVTLVP YSKNGEQKTK PTQHSVKELR SIGLQPDILV GRCSDKLDID TKEKIALFCD
VPTEAVFSNP DVDDIYHVPL MVEEEGLDQY VMEELDIATE ALPEDERENR WRDLVTQNTE
GEVDIALVGK YDLEDAYMSV HEALKHAGLE KNVDVNVQWV NSEKMNDHHA DRMREADAIV
VPGGFGARGT EGKIEAIRYA RENDIPFLGL CLGFQMAVVE YARNVLDLDD AHSAELDEDT
PHPVIDILPE QYEIEDMGGT MRLGAHETEI DANTLAATLY GGESCTERHR HRYEVNPEYI
DDLEAAGLKF SGYAENRMEI LELAPEDHPY FIGTQFHPEF RSRPTRASPP FVGLLEAVLG
DDPHTVTTEE VSH
