PYRG_HERAR
ID PYRG_HERAR Reviewed; 552 AA.
AC A4G738;
DT 14-APR-2009, integrated into UniProtKB/Swiss-Prot.
DT 17-APR-2007, sequence version 1.
DT 03-AUG-2022, entry version 92.
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=HEAR2189;
OS Herminiimonas arsenicoxydans.
OC Bacteria; Proteobacteria; Betaproteobacteria; Burkholderiales;
OC Oxalobacteraceae; Herminiimonas.
OX NCBI_TaxID=204773;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ULPAs1;
RX PubMed=17432936; DOI=10.1371/journal.pgen.0030053;
RA Muller D., Medigue C., Koechler S., Barbe V., Barakat M., Talla E.,
RA Bonnefoy V., Krin E., Arsene-Ploetze F., Carapito C., Chandler M.,
RA Cournoyer B., Cruveiller S., Dossat C., Duval S., Heymann M., Leize E.,
RA Lieutaud A., Lievremont D., Makita Y., Mangenot S., Nitschke W., Ortet P.,
RA Perdrial N., Schoepp B., Siguier P., Simeonova D.D., Rouy Z., Segurens B.,
RA Turlin E., Vallenet D., van Dorsselaer A., Weiss S., Weissenbach J.,
RA Lett M.-C., Danchin A., Bertin P.N.;
RT "A tale of two oxidation states: bacterial colonization of arsenic-rich
RT environments.";
RL PLoS Genet. 3:518-530(2007).
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; CU207211; CAL62325.1; -; Genomic_DNA.
DR RefSeq; WP_011871597.1; NC_009138.1.
DR AlphaFoldDB; A4G738; -.
DR SMR; A4G738; -.
DR STRING; 204773.HEAR2189; -.
DR MEROPS; C26.964; -.
DR EnsemblBacteria; CAL62325; CAL62325; HEAR2189.
DR KEGG; har:HEAR2189; -.
DR eggNOG; COG0504; Bacteria.
DR HOGENOM; CLU_011675_5_0_4; -.
DR OMA; EFNNAYR; -.
DR OrthoDB; 783657at2; -.
DR UniPathway; UPA00159; UER00277.
DR Proteomes; UP000006697; 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..552
FT /note="CTP synthase"
FT /id="PRO_1000139472"
FT DOMAIN 290..545
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 518
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT ACT_SITE 520
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 468
FT /ligand="L-glutamine"
FT /ligand_id="ChEBI:CHEBI:58359"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
SQ SEQUENCE 552 AA; 60884 MW; 344C24D5B8B2107E CRC64;
MTKFVFVTGG VVSSLGKGIA AASLAAILES RGLKVTLLKL DPYINVDPGT MSPFQHGEVF
VTEDGAETDL DLGHYERFIT AKMRKVNNFT TGQIYESVIR KERRGEYLGK TVQVIPHITN
EIQDYIYRGA EGFDVALVEI GGTVGDIESL PFLEAARQLS LRAGRNAAAF VHLTLVPYLV
SAGELKTKPT QHSVQKLREI GISPDALLCR ADRPIPDDER AKISLFSNVP EDAVISVWDA
DTIYKIPQML YDQGLDRIVC EKLALSPKPA DLSVWTKLVH ALENPKHSVT IGMVGKYVDL
TESYKSLTEA LRHAGIHTES RVNIEYLDSE EIEASGPQCL AKYDAILVPG GFGKRGVEGK
IAAARFAREH AIPYFGICLG MQVALIEYAR NVAGLTKANS TEFDPDTEQP VVALINEWQN
HDGKVERRDL NSDLGGTMRL GSQTCAVKPG TLAAEIYGNE VTERHRHRYE ANNHYLGRVE
EAGLIVSART PAESLCEIME LPRTGEHAHP WYVGVQYHPE FNSTPRDGHP LFISFIKAAL
AHKQAEESKK VT
