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Protein

CTP synthase

Gene

pyrG

Organism
Lactococcus lactis subsp. cremoris (strain MG1363)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Catalyzes the ATP-dependent amination of UTP to CTP with either L-glutamine or ammonia as the source of nitrogen. Is essential for the synthesis of CTP de novo. Contrary to other bacterial CTP synthases, the lactococcal enzyme is also able to convert dUTP to dCTP, but this reaction may not play a significant physiological role (PubMed:11500486). Regulates intracellular CTP levels through interactions with the four ribonucleotide triphosphates (By similarity).UniRule annotation1 Publication

Catalytic activityi

ATP + UTP + L-glutamine = ADP + phosphate + CTP + L-glutamate.UniRule annotation1 Publication

Enzyme regulationi

Allosterically activated by GTP, when glutamine is the substrate (PubMed:11500486). GTP has no effect on the reaction when ammonia is the substrate. The allosteric effector GTP functions by stabilizing the protein conformation that binds the tetrahedral intermediate(s) formed during glutamine hydrolysis (By similarity). Also activated by magnesium (PubMed:11500486). Allosterically inhibited by CTP (PubMed:11500486).UniRule annotation1 Publication

Kineticsi

  1. KM=0.52 mM for L-glutamine1 Publication
  2. KM=42.9 mM for ammonia1 Publication

    Pathwayi: CTP biosynthesis via de novo pathway

    This protein is involved in step 2 of the subpathway that synthesizes CTP from UDP.UniRule annotation1 Publication
    Proteins known to be involved in the 2 steps of the subpathway in this organism are:
    1. no protein annotated in this organism
    2. CTP synthase (pyrG)
    This subpathway is part of the pathway CTP biosynthesis via de novo pathway, which is itself part of Pyrimidine metabolism.
    View all proteins of this organism that are known to be involved in the subpathway that synthesizes CTP from UDP, the pathway CTP biosynthesis via de novo pathway and in Pyrimidine metabolism.

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei14 – 141Allosteric inhibitor CTP; alternateUniRule annotation
    Binding sitei14 – 141UTP; alternateUniRule annotation
    Binding sitei55 – 551L-glutamineUniRule annotation
    Metal bindingi72 – 721MagnesiumUniRule annotation
    Binding sitei72 – 721ATPUniRule annotation
    Metal bindingi142 – 1421MagnesiumUniRule annotation
    Binding sitei225 – 2251Allosteric inhibitor CTP; alternateUniRule annotation
    Binding sitei225 – 2251UTP; alternateUniRule annotation
    Binding sitei243 – 2431ATP; via amide nitrogenUniRule annotation
    Binding sitei355 – 3551L-glutamine; via carbonyl oxygenUniRule annotation
    Active sitei382 – 3821Nucleophile; for glutamine hydrolysisUniRule annotation
    Binding sitei406 – 4061L-glutamineUniRule annotation
    Binding sitei464 – 4641L-glutamine; via amide nitrogenUniRule annotation
    Active sitei509 – 5091UniRule annotation
    Active sitei511 – 5111UniRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi15 – 206ATPUniRule annotation
    Nucleotide bindingi149 – 1513Allosteric inhibitor CTPUniRule annotation
    Nucleotide bindingi189 – 1946Allosteric inhibitor CTP; alternateUniRule annotation
    Nucleotide bindingi189 – 1946UTP; alternateUniRule annotation

    GO - Molecular functioni

    GO - Biological processi

    Complete GO annotation...

    Keywords - Molecular functioni

    Ligase

    Keywords - Biological processi

    Pyrimidine biosynthesis

    Keywords - Ligandi

    ATP-binding, Magnesium, Metal-binding, Nucleotide-binding

    Enzyme and pathway databases

    BioCyciLLAC416870:GCDT-480-MONOMER.
    SABIO-RKO87761.
    UniPathwayiUPA00159; UER00277.

    Protein family/group databases

    MEROPSiC26.964.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    CTP synthase1 PublicationUniRule annotation (EC:6.3.4.2UniRule annotation1 Publication)
    Alternative name(s):
    Cytidine 5'-triphosphate synthaseUniRule annotation
    Cytidine triphosphate synthetaseUniRule annotation
    Short name:
    CTP synthetaseUniRule annotation
    Short name:
    CTPSUniRule annotation
    UTP--ammonia ligaseUniRule annotation
    Gene namesi
    Name:pyrGUniRule annotation
    Ordered Locus Names:llmg_0467
    OrganismiLactococcus lactis subsp. cremoris (strain MG1363)
    Taxonomic identifieri416870 [NCBI]
    Taxonomic lineageiBacteriaFirmicutesBacilliLactobacillalesStreptococcaceaeLactococcus
    Proteomesi
    • UP000000364 Componenti: Chromosome

    Pathology & Biotechi

    Disruption phenotypei

    Cells lacking this gene require cytidine for growth, proving that in L.lactis, the pyrG product is the only enzyme responsible for the amination of UTP to CTP.1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 535535CTP synthasePRO_0000138192Add
    BLAST

    Interactioni

    Subunit structurei

    Homotetramer. In contrast to E.coli CTP synthase, remains a tetramer at dilute enzyme concentrations even in the absence of Mg2+, ATP and UTP.1 Publication

    Protein-protein interaction databases

    STRINGi416870.llmg_0467.

    Structurei

    3D structure databases

    ProteinModelPortaliO87761.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini293 – 535243Glutamine amidotransferase type-1UniRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni1 – 268268Amidoligase domainUniRule annotationAdd
    BLAST
    Regioni383 – 3864L-glutamine bindingUniRule annotation

    Sequence similaritiesi

    Belongs to the CTP synthase family.UniRule annotation
    Contains 1 glutamine amidotransferase type-1 domain.UniRule annotation

    Keywords - Domaini

    Glutamine amidotransferase

    Phylogenomic databases

    eggNOGiENOG4105C8D. Bacteria.
    COG0504. LUCA.
    HOGENOMiHOG000077515.
    KOiK01937.
    OMAiFDHNITT.
    OrthoDBiEOG6RC3NR.

    Family and domain databases

    Gene3Di3.40.50.300. 1 hit.
    3.40.50.880. 1 hit.
    HAMAPiMF_01227. PyrG.
    InterProiIPR029062. Class_I_gatase-like.
    IPR004468. CTP_synthase.
    IPR017456. CTP_synthase_N.
    IPR017926. GATASE.
    IPR027417. P-loop_NTPase.
    [Graphical view]
    PANTHERiPTHR11550. PTHR11550. 1 hit.
    PfamiPF06418. CTP_synth_N. 1 hit.
    PF00117. GATase. 1 hit.
    [Graphical view]
    SUPFAMiSSF52317. SSF52317. 1 hit.
    SSF52540. SSF52540. 1 hit.
    TIGRFAMsiTIGR00337. PyrG. 1 hit.
    PROSITEiPS51273. GATASE_TYPE_1. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    O87761-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MSTKYIFVTG GGTSSMGKGI VAASLGRLLK NRGLKVTVQK FDPYLNIDPG
    60 70 80 90 100
    TMSPYQHGEV FVTDDGAETD LDLGHYERFI DINLNKYSNV TSGKVYSEIL
    110 120 130 140 150
    RKERKGEYLG ATVQMVPHVT NMLKEKIKRA ATTTDADIII TEVGGTVGDM
    160 170 180 190 200
    ESLPFIEALR QMKAEVGADN VMYIHTVPIL HLRAAGELKT KIAQNATKTL
    210 220 230 240 250
    REYGIQANML VLRSEVPITT EMRDKIAMFC DVAPEAVIQS LDVEHLYQIP
    260 270 280 290 300
    LNLQAQNMDQ IVCDHLKLDA PKADMAEWSA MVDHVMNLKK KVKIALVGKY
    310 320 330 340 350
    VELPDAYISV TEALKHAGYA SDAEVDINWV NANDVTDENV AELVGDAAGI
    360 370 380 390 400
    IVPGGFGQRG TEGKIAAIKY ARENDVPMLG ICLGMQLTAV EFARNVLGLE
    410 420 430 440 450
    GAHSFELDPE TKYPVIDIMR DQVDVEDMGG TLRLGLYPAK LKNGSRAKAA
    460 470 480 490 500
    YNDAEVVQRR HRHRYEFNNK YREDFEKAGF VFSGVSPDNR LVEIVELSGK
    510 520 530
    KFFVACQYHP ELQSRPNRPE ELYTEFIRVA VENSK
    Length:535
    Mass (Da):59,455
    Last modified:October 1, 2000 - v2
    Checksum:i045724E0FEDE5B4E
    GO

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AJ010153 Genomic DNA. Translation: CAA09021.2.
    AM406671 Genomic DNA. Translation: CAL97071.1.
    RefSeqiWP_011834508.1. NC_009004.1.

    Genome annotation databases

    EnsemblBacteriaiCAL97071; CAL97071; llmg_0467.
    KEGGillm:llmg_0467.
    PATRICi22281985. VBILacLac4574_0478.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AJ010153 Genomic DNA. Translation: CAA09021.2.
    AM406671 Genomic DNA. Translation: CAL97071.1.
    RefSeqiWP_011834508.1. NC_009004.1.

    3D structure databases

    ProteinModelPortaliO87761.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    STRINGi416870.llmg_0467.

    Protein family/group databases

    MEROPSiC26.964.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsemblBacteriaiCAL97071; CAL97071; llmg_0467.
    KEGGillm:llmg_0467.
    PATRICi22281985. VBILacLac4574_0478.

    Phylogenomic databases

    eggNOGiENOG4105C8D. Bacteria.
    COG0504. LUCA.
    HOGENOMiHOG000077515.
    KOiK01937.
    OMAiFDHNITT.
    OrthoDBiEOG6RC3NR.

    Enzyme and pathway databases

    UniPathwayiUPA00159; UER00277.
    BioCyciLLAC416870:GCDT-480-MONOMER.
    SABIO-RKO87761.

    Family and domain databases

    Gene3Di3.40.50.300. 1 hit.
    3.40.50.880. 1 hit.
    HAMAPiMF_01227. PyrG.
    InterProiIPR029062. Class_I_gatase-like.
    IPR004468. CTP_synthase.
    IPR017456. CTP_synthase_N.
    IPR017926. GATASE.
    IPR027417. P-loop_NTPase.
    [Graphical view]
    PANTHERiPTHR11550. PTHR11550. 1 hit.
    PfamiPF06418. CTP_synth_N. 1 hit.
    PF00117. GATase. 1 hit.
    [Graphical view]
    SUPFAMiSSF52317. SSF52317. 1 hit.
    SSF52540. SSF52540. 1 hit.
    TIGRFAMsiTIGR00337. PyrG. 1 hit.
    PROSITEiPS51273. GATASE_TYPE_1. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Publicationsi

    « Hide 'large scale' publications
    1. "Cloning and verification of the Lactococcus lactis pyrG gene and characterization of the gene product, CTP synthase."
      Wadskov-Hansen S.L.L., Willemoes M., Martinussen J., Hammer K., Neuhard J., Larsen S.
      J. Biol. Chem. 276:38002-38009(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, ENZYME REGULATION, DISRUPTION PHENOTYPE, SUBUNIT, PATHWAY.
      Strain: MG1363.
    2. "The complete genome sequence of the lactic acid bacterial paradigm Lactococcus lactis subsp. cremoris MG1363."
      Wegmann U., O'Connell-Motherway M., Zomer A., Buist G., Shearman C., Canchaya C., Ventura M., Goesmann A., Gasson M.J., Kuipers O.P., van Sinderen D., Kok J.
      J. Bacteriol. 189:3256-3270(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: MG1363.

    Entry informationi

    Entry nameiPYRG_LACLM
    AccessioniPrimary (citable) accession number: O87761
    Secondary accession number(s): A2RIH6
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: October 19, 2002
    Last sequence update: October 1, 2000
    Last modified: July 6, 2016
    This is version 93 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programProkaryotic Protein Annotation Program

    Miscellaneousi

    Miscellaneous

    CTPSs have evolved a hybrid strategy for distinguishing between UTP and CTP. The overlapping regions of the product feedback inhibitory and substrate sites recognize a common feature in both compounds, the triphosphate moiety. To differentiate isosteric substrate and product pyrimidine rings, an additional pocket far from the expected kinase/ligase catalytic site, specifically recognizes the cytosine and ribose portions of the product inhibitor.UniRule annotation

    Keywords - Technical termi

    Complete proteome

    Documents

    1. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    2. SIMILARITY comments
      Index of protein domains and families

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.