Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

CTP synthase

Gene

pyrG

Organism
Escherichia coli (strain K12)
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. Regulates intracellular CTP levels through interactions with the four ribonucleotide triphosphates.1 Publication2 Publications

Catalytic activityi

ATP + UTP + L-glutamine = ADP + phosphate + CTP + L-glutamate.3 Publications

Enzyme regulationi

Allosterically activated by GTP, when glutamine is the substrate; GTP has no effect on the reaction when ammonia is the substrate (PubMed:4550559). The allosteric effector GTP functions by stabilizing the protein conformation that binds the tetrahedral intermediate(s) formed during glutamine hydrolysis (PubMed:11336655). Also activated by magnesium; the enzyme requires more Mg2+ for full catalytic activity than required simply to complex the nucleotide substrates (PubMed:8385490). Inhibited by the product CTP, via allosteric rather than competitive inhibition (PubMed:8385490, PubMed:16216072). Also inhibited by divalent metal ions such as copper and zinc (PubMed:8385490). Is potently inhibited by the intermediate analog inhibitor glutamate gamma-semialdehyde (PubMed:11336655).1 Publication3 Publications

Kineticsi

kcat is 13 sec(-1) with ammonia as substrate. kcat is 6.6 sec(-1) with L-glutamine as substrate (in the presence of 0.25 mM GTP).1 Publication

Manual assertion based on experiment ini

  1. KM=2.0 mM for ammonia1 Publication
  2. KM=0.30 mM for L-glutamine (in the presence of 0.25 mM GTP)1 Publication

    pH dependencei

    Optimum pH is 8.7.1 Publication

    Pathwayi: CTP biosynthesis via de novo pathway

    This protein is involved in step 2 of the subpathway that synthesizes CTP from UDP.UniRule annotation
    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)DescriptionActionsGraphical viewLength
    Binding sitei14Allosteric inhibitor CTP; alternate1 Publication1
    Binding sitei14UTP; alternate1 Publication1
    Metal bindingi72MagnesiumCombined sources1 Publication1
    Binding sitei72ATPCombined sources1 Publication1
    Metal bindingi140MagnesiumCombined sources1 Publication1
    Binding sitei223Allosteric inhibitor CTP; alternateCombined sources1 Publication1
    Binding sitei223UTP; alternate1 Publication1
    Binding sitei352L-glutamine; via carbonyl oxygenUniRule annotation1
    Active sitei379Nucleophile; for glutamine hydrolysis2 Publications1
    Binding sitei403L-glutamineUniRule annotation1
    Binding sitei470L-glutamine; via amide nitrogenUniRule annotation1
    Active sitei5151 Publication1
    Active sitei5171 Publication1

    Regions

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Nucleotide bindingi15 – 20ATPCombined sources1 Publication6
    Nucleotide bindingi147 – 149Allosteric inhibitor CTPCombined sources1 Publication3
    Nucleotide bindingi187 – 192Allosteric inhibitor CTP; alternateCombined sources1 Publication6
    Nucleotide bindingi187 – 192UTP; alternate1 Publication6
    Nucleotide bindingi239 – 241ATPCombined sources1 Publication3

    GO - Molecular functioni

    • ATP binding Source: UniProtKB-KW
    • CTP synthase activity Source: EcoCyc
    • identical protein binding Source: EcoCyc
    • metal ion binding Source: UniProtKB-KW

    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

    BioCyciEcoCyc:CTPSYN-MONOMER.
    ECOL316407:JW2751-MONOMER.
    MetaCyc:CTPSYN-MONOMER.
    BRENDAi6.3.4.2. 2026.
    UniPathwayiUPA00159; UER00277.

    Protein family/group databases

    MEROPSiC26.964.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    CTP synthase1 Publication (EC:6.3.4.23 Publications)
    Alternative name(s):
    Cytidine 5'-triphosphate synthase1 Publication
    Cytidine triphosphate synthetase1 Publication
    Short name:
    CTP synthetase1 Publication
    Short name:
    CTPS1 Publication
    UTP--ammonia ligase
    Gene namesi
    Name:pyrG1 Publication
    Ordered Locus Names:b2780, JW2751
    OrganismiEscherichia coli (strain K12)
    Taxonomic identifieri83333 [NCBI]
    Taxonomic lineageiBacteriaProteobacteriaGammaproteobacteriaEnterobacteralesEnterobacteriaceaeEscherichia
    Proteomesi
    • UP000000318 Componenti: Chromosome
    • UP000000625 Componenti: Chromosome

    Organism-specific databases

    EcoGeneiEG10810. pyrG.

    Subcellular locationi

    GO - Cellular componenti

    • cytosol Source: UniProtKB
    Complete GO annotation...

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi349V → S: 30% increase in both glutamine-dependent and ammonia-dependent activities. 1 Publication1
    Mutagenesisi352G → P: Loss of glutamine-dependent activity, but no change in ammonia-dependent activity. 1 Publication1
    Mutagenesisi379C → A or S: Loss of glutamine-dependent activity, but no change in ammonia-dependent activity. 1 Publication1

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Initiator methionineiRemoved1 Publication
    ChainiPRO_00001381832 – 545CTP synthaseAdd BLAST544

    Proteomic databases

    EPDiP0A7E5.
    PaxDbiP0A7E5.
    PRIDEiP0A7E5.

    2D gel databases

    SWISS-2DPAGEP0A7E5.

    Interactioni

    Subunit structurei

    Homodimer that associates to form homotetramer in the presence of ATP and UTP. The substrate nucleotides ATP and UTP act synergistically to promote oligomerization of CTPS from inactive dimers to active tetramers.1 Publication

    GO - Molecular functioni

    • identical protein binding Source: EcoCyc

    Protein-protein interaction databases

    DIPiDIP-10628N.
    IntActiP0A7E5. 8 interactors.
    STRINGi511145.b2780.

    Structurei

    Secondary structure

    1545
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Beta strandi4 – 10Combined sources7
    Beta strandi12 – 14Combined sources3
    Helixi18 – 30Combined sources13
    Turni31 – 33Combined sources3
    Beta strandi36 – 42Combined sources7
    Helixi49 – 51Combined sources3
    Turni54 – 56Combined sources3
    Beta strandi60 – 62Combined sources3
    Beta strandi68 – 70Combined sources3
    Helixi72 – 79Combined sources8
    Helixi86 – 88Combined sources3
    Beta strandi89 – 91Combined sources3
    Helixi92 – 104Combined sources13
    Turni105 – 110Combined sources6
    Helixi115 – 131Combined sources17
    Beta strandi135 – 141Combined sources7
    Helixi148 – 150Combined sources3
    Helixi151 – 164Combined sources14
    Beta strandi168 – 176Combined sources9
    Turni181 – 184Combined sources4
    Helixi189 – 199Combined sources11
    Turni200 – 202Combined sources3
    Beta strandi206 – 214Combined sources9
    Helixi218 – 226Combined sources9
    Helixi232 – 234Combined sources3
    Beta strandi235 – 239Combined sources5
    Helixi244 – 246Combined sources3
    Helixi247 – 253Combined sources7
    Helixi256 – 263Combined sources8
    Helixi274 – 284Combined sources11
    Beta strandi287 – 298Combined sources12
    Helixi302 – 305Combined sources4
    Helixi306 – 318Combined sources13
    Beta strandi321 – 329Combined sources9
    Helixi330 – 336Combined sources7
    Turni338 – 343Combined sources6
    Beta strandi345 – 349Combined sources5
    Helixi358 – 370Combined sources13
    Beta strandi375 – 378Combined sources4
    Helixi380 – 394Combined sources15
    Turni402 – 404Combined sources3
    Beta strandi411 – 414Combined sources4
    Turni416 – 418Combined sources3
    Beta strandi440 – 448Combined sources9
    Helixi453 – 457Combined sources5
    Beta strandi460 – 469Combined sources10
    Helixi475 – 483Combined sources9
    Beta strandi487 – 491Combined sources5
    Beta strandi493 – 495Combined sources3
    Beta strandi498 – 502Combined sources5
    Beta strandi506 – 514Combined sources9
    Helixi516 – 518Combined sources3
    Turni522 – 524Combined sources3
    Helixi527 – 542Combined sources16

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    1S1MX-ray2.30A/B1-545[»]
    2AD5X-ray2.80A/B1-545[»]
    ProteinModelPortaliP0A7E5.
    SMRiP0A7E5.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP0A7E5.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Domaini291 – 542Glutamine amidotransferase type-1UniRule annotationAdd BLAST252

    Region

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Regioni2 – 266Amidoligase domain1 PublicationAdd BLAST265
    Regioni380 – 383L-glutamine bindingUniRule annotation4

    Domaini

    Sequence consists of two domains: the C-terminal glutamine amide transfer (GAT) domain catalyzes the hydrolysis of glutamine; the N-terminal synthase domain catalyzes the amination of UTP (PubMed:3514618, PubMed:3298209). Structure shows each subunit consists of three distinct segments: the N-terminal amidoligase (ALase) domain, which mediates oligomerization and contains the ALase active site where ATP and UTP substrates bind, and an interrupted helical interdomain linker segment that connects the ALase domain to the Type I glutamine amidotransferase (GATase) C-terminal domain, which generates ammonia via glutamine hydrolysis (PubMed:15157079). A gated channel that spans 25 Angstroms between the glutamine hydrolysis and amidoligase active sites provides a path for ammonia diffusion; the channel is accessible to solvent at the base of a cleft adjoining the glutamine hydrolysis active site, providing an entry point for exogenous ammonia (PubMed:15157079).3 Publications

    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.
    InParanoidiP0A7E5.
    KOiK01937.
    OMAiTMRLGEY.
    PhylomeDBiP0A7E5.

    Family and domain databases

    CDDicd01746. GATase1_CTP_Synthase. 1 hit.
    Gene3Di3.40.50.300. 1 hit.
    3.40.50.880. 1 hit.
    HAMAPiMF_01227. PyrG. 1 hit.
    InterProiIPR029062. Class_I_gatase-like.
    IPR004468. CTP_synthase.
    IPR017456. CTP_synthase_N.
    IPR017926. GATASE.
    IPR033828. GATase1_CTP_Synthase.
    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.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    P0A7E5-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MTTNYIFVTG GVVSSLGKGI AAASLAAILE ARGLNVTIMK LDPYINVDPG
    60 70 80 90 100
    TMSPIQHGEV FVTEDGAETD LDLGHYERFI RTKMSRRNNF TTGRIYSDVL
    110 120 130 140 150
    RKERRGDYLG ATVQVIPHIT NAIKERVLEG GEGHDVVLVE IGGTVGDIES
    160 170 180 190 200
    LPFLEAIRQM AVEIGREHTL FMHLTLVPYM AASGEVKTKP TQHSVKELLS
    210 220 230 240 250
    IGIQPDILIC RSDRAVPANE RAKIALFCNV PEKAVISLKD VDSIYKIPGL
    260 270 280 290 300
    LKSQGLDDYI CKRFSLNCPE ANLSEWEQVI FEEANPVSEV TIGMVGKYIE
    310 320 330 340 350
    LPDAYKSVIE ALKHGGLKNR VSVNIKLIDS QDVETRGVEI LKGLDAILVP
    360 370 380 390 400
    GGFGYRGVEG MITTARFARE NNIPYLGICL GMQVALIDYA RHVANMENAN
    410 420 430 440 450
    STEFVPDCKY PVVALITEWR DENGNVEVRS EKSDLGGTMR LGAQQCQLVD
    460 470 480 490 500
    DSLVRQLYNA PTIVERHRHR YEVNNMLLKQ IEDAGLRVAG RSGDDQLVEI
    510 520 530 540
    IEVPNHPWFV ACQFHPEFTS TPRDGHPLFA GFVKAASEFQ KRQAK
    Length:545
    Mass (Da):60,374
    Last modified:January 23, 2007 - v2
    Checksum:iFBB9E2E18FA355FC
    GO

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti338V → L in AAA24485 (PubMed:3514618).Curated1
    Sequence conflicti476M → S in AAA24485 (PubMed:3514618).Curated1

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    M12843 mRNA. Translation: AAA24485.1.
    U29580 Genomic DNA. Translation: AAA69290.1.
    U00096 Genomic DNA. Translation: AAC75822.1.
    AP009048 Genomic DNA. Translation: BAE76854.1.
    PIRiH65059. SYECTP.
    RefSeqiNP_417260.1. NC_000913.3.
    WP_000210878.1. NZ_LN832404.1.

    Genome annotation databases

    EnsemblBacteriaiAAC75822; AAC75822; b2780.
    BAE76854; BAE76854; BAE76854.
    GeneIDi946116.
    KEGGiecj:JW2751.
    eco:b2780.
    PATRICi32120976. VBIEscCol129921_2880.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    M12843 mRNA. Translation: AAA24485.1.
    U29580 Genomic DNA. Translation: AAA69290.1.
    U00096 Genomic DNA. Translation: AAC75822.1.
    AP009048 Genomic DNA. Translation: BAE76854.1.
    PIRiH65059. SYECTP.
    RefSeqiNP_417260.1. NC_000913.3.
    WP_000210878.1. NZ_LN832404.1.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    1S1MX-ray2.30A/B1-545[»]
    2AD5X-ray2.80A/B1-545[»]
    ProteinModelPortaliP0A7E5.
    SMRiP0A7E5.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    DIPiDIP-10628N.
    IntActiP0A7E5. 8 interactors.
    STRINGi511145.b2780.

    Protein family/group databases

    MEROPSiC26.964.

    2D gel databases

    SWISS-2DPAGEP0A7E5.

    Proteomic databases

    EPDiP0A7E5.
    PaxDbiP0A7E5.
    PRIDEiP0A7E5.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsemblBacteriaiAAC75822; AAC75822; b2780.
    BAE76854; BAE76854; BAE76854.
    GeneIDi946116.
    KEGGiecj:JW2751.
    eco:b2780.
    PATRICi32120976. VBIEscCol129921_2880.

    Organism-specific databases

    EchoBASEiEB0803.
    EcoGeneiEG10810. pyrG.

    Phylogenomic databases

    eggNOGiENOG4105C8D. Bacteria.
    COG0504. LUCA.
    HOGENOMiHOG000077515.
    InParanoidiP0A7E5.
    KOiK01937.
    OMAiTMRLGEY.
    PhylomeDBiP0A7E5.

    Enzyme and pathway databases

    UniPathwayiUPA00159; UER00277.
    BioCyciEcoCyc:CTPSYN-MONOMER.
    ECOL316407:JW2751-MONOMER.
    MetaCyc:CTPSYN-MONOMER.
    BRENDAi6.3.4.2. 2026.

    Miscellaneous databases

    EvolutionaryTraceiP0A7E5.
    PROiP0A7E5.

    Family and domain databases

    CDDicd01746. GATase1_CTP_Synthase. 1 hit.
    Gene3Di3.40.50.300. 1 hit.
    3.40.50.880. 1 hit.
    HAMAPiMF_01227. PyrG. 1 hit.
    InterProiIPR029062. Class_I_gatase-like.
    IPR004468. CTP_synthase.
    IPR017456. CTP_synthase_N.
    IPR017926. GATASE.
    IPR033828. GATase1_CTP_Synthase.
    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...

    Entry informationi

    Entry nameiPYRG_ECOLI
    AccessioniPrimary (citable) accession number: P0A7E5
    Secondary accession number(s): P08398, Q2MA52
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: August 1, 1988
    Last sequence update: January 23, 2007
    Last modified: November 30, 2016
    This is version 107 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.1 Publication

    Keywords - Technical termi

    3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. Escherichia coli
      Escherichia coli (strain K12): entries and cross-references to EcoGene
    2. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    3. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    4. 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.