UniProtKB - P0A7E5 (PYRG_ECOLI)
Protein
CTP synthase
Gene
pyrG
Organism
Escherichia coli (strain K12)
Status
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
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
Catalytic activityi
- EC:6.3.4.23 Publications
Activity 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
- KM=2.0 mM for ammonia1 Publication
- 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
: CTP biosynthesis via de novo pathway Pathwayi
This protein is involved in step 2 of the subpathway that synthesizes CTP from UDP.UniRule annotationProteins known to be involved in the 2 steps of the subpathway in this organism are:
- no protein annotated in this organism
- CTP synthase (pyrG), CTP synthase (pyrG)
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 key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 14 | CTP; allosteric inhibitor; alternate1 Publication | 1 | |
Binding sitei | 14 | UTP; alternate1 Publication | 1 | |
Metal bindingi | 72 | MagnesiumCombined sources1 Publication | 1 | |
Binding sitei | 72 | ATPCombined sources1 Publication | 1 | |
Metal bindingi | 140 | MagnesiumCombined sources1 Publication | 1 | |
Binding sitei | 223 | CTP; allosteric inhibitor; alternateCombined sources1 Publication | 1 | |
Binding sitei | 223 | UTP; alternate1 Publication | 1 | |
Binding sitei | 352 | L-glutamine; via carbonyl oxygenUniRule annotation | 1 | |
Active sitei | 379 | Nucleophile; for glutamine hydrolysis2 Publications | 1 | |
Binding sitei | 403 | L-glutamineUniRule annotation | 1 | |
Binding sitei | 470 | L-glutamine; via amide nitrogenUniRule annotation | 1 | |
Active sitei | 515 | 1 Publication | 1 | |
Active sitei | 517 | 1 Publication | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 15 – 20 | ATPCombined sources1 Publication | 6 | |
Nucleotide bindingi | 147 – 149 | CTP; allosteric inhibitorCombined sources1 Publication | 3 | |
Nucleotide bindingi | 187 – 192 | CTP; allosteric inhibitor; alternateCombined sources1 Publication | 6 | |
Nucleotide bindingi | 187 – 192 | UTP; alternate1 Publication | 6 | |
Nucleotide bindingi | 239 – 241 | ATPCombined sources1 Publication | 3 |
GO - Molecular functioni
- ATP binding Source: UniProtKB-KW
- CTP synthase activity Source: EcoCyc
- identical protein binding Source: EcoCyc
- magnesium ion binding Source: EcoCyc
GO - Biological processi
- 'de novo' CTP biosynthetic process Source: UniProtKB-UniPathway
- CTP biosynthetic process Source: EcoCyc
- glutamine metabolic process Source: UniProtKB-KW
- protein homotetramerization Source: EcoCyc
- pyrimidine nucleobase biosynthetic process Source: GO_Central
Keywordsi
Molecular function | Ligase |
Biological process | Pyrimidine biosynthesis |
Ligand | ATP-binding, Magnesium, Metal-binding, Nucleotide-binding |
Enzyme and pathway databases
BioCyci | EcoCyc:CTPSYN-MONOMER MetaCyc:CTPSYN-MONOMER |
BRENDAi | 6.3.4.2, 2026 |
UniPathwayi | UPA00159;UER00277 |
Protein family/group databases
MEROPSi | C26.964 |
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 |
Organismi | Escherichia coli (strain K12) |
Taxonomic identifieri | 83333 [NCBI] |
Taxonomic lineagei | Bacteria › Proteobacteria › Gammaproteobacteria › Enterobacterales › Enterobacteriaceae › Escherichia › |
Proteomesi |
|
Subcellular locationi
Cytoplasm and Cytosol
- Cytoplasm 1 Publication
Note: Localizes to the cytoophidium, a subcellular filamentary structure where CTP synthase is compartmentalized. Many cells form cytoophidia which are observed in stationary phase.1 Publication
Cytosol
- cytosol Source: EcoCyc
Other locations
- cytoophidium Source: UniProtKB
Keywords - Cellular componenti
CytoplasmPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 349 | V → S: 30% increase in both glutamine-dependent and ammonia-dependent activities. 1 Publication | 1 | |
Mutagenesisi | 352 | G → P: Loss of glutamine-dependent activity, but no change in ammonia-dependent activity. 1 Publication | 1 | |
Mutagenesisi | 379 | C → A or S: Loss of glutamine-dependent activity, but no change in ammonia-dependent activity. 1 Publication | 1 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Initiator methioninei | Removed1 Publication | |||
ChainiPRO_0000138183 | 2 – 545 | CTP synthaseAdd BLAST | 544 |
Proteomic databases
jPOSTi | P0A7E5 |
PaxDbi | P0A7E5 |
PRIDEi | P0A7E5 |
2D gel databases
SWISS-2DPAGEi | P0A7E5 |
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 PublicationGO - Molecular functioni
- identical protein binding Source: EcoCyc
Protein-protein interaction databases
BioGRIDi | 4262298, 5 interactors |
DIPi | DIP-10628N |
IntActi | P0A7E5, 8 interactors |
STRINGi | 511145.b2780 |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | P0A7E5 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P0A7E5 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 291 – 542 | Glutamine amidotransferase type-1UniRule annotationAdd BLAST | 252 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 2 – 266 | Amidoligase domain1 PublicationAdd BLAST | 265 | |
Regioni | 380 – 383 | L-glutamine bindingUniRule annotation | 4 |
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
Keywords - Domaini
Glutamine amidotransferasePhylogenomic databases
eggNOGi | COG0504, Bacteria |
HOGENOMi | CLU_011675_5_0_6 |
InParanoidi | P0A7E5 |
PhylomeDBi | P0A7E5 |
Family and domain databases
CDDi | cd03113, CTPS_N, 1 hit cd01746, GATase1_CTP_Synthase, 1 hit |
Gene3Di | 3.40.50.880, 1 hit |
HAMAPi | MF_01227, PyrG, 1 hit |
InterProi | View protein in InterPro IPR029062, Class_I_gatase-like IPR004468, CTP_synthase IPR017456, CTP_synthase_N IPR017926, GATASE IPR033828, GATase1_CTP_Synthase IPR027417, P-loop_NTPase |
PANTHERi | PTHR11550, PTHR11550, 1 hit |
Pfami | View protein in Pfam PF06418, CTP_synth_N, 1 hit PF00117, GATase, 1 hit |
SUPFAMi | SSF52317, SSF52317, 1 hit SSF52540, SSF52540, 1 hit |
TIGRFAMsi | TIGR00337, PyrG, 1 hit |
PROSITEi | View protein in PROSITE PS51273, GATASE_TYPE_1, 1 hit |
i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
P0A7E5-1 [UniParc]FASTAAdd to basket
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
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 338 | V → L in AAA24485 (PubMed:3514618).Curated | 1 | |
Sequence conflicti | 476 | M → S in AAA24485 (PubMed:3514618).Curated | 1 |
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 |
PIRi | H65059, SYECTP |
RefSeqi | NP_417260.1, NC_000913.3 WP_000210878.1, NZ_STEB01000030.1 |
Genome annotation databases
EnsemblBacteriai | AAC75822; AAC75822; b2780 BAE76854; BAE76854; BAE76854 |
GeneIDi | 58459987 946116 |
KEGGi | ecj:JW2751 eco:b2780 |
PATRICi | fig|1411691.4.peg.3955 |
Similar proteinsi
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 |
PIRi | H65059, SYECTP |
RefSeqi | NP_417260.1, NC_000913.3 WP_000210878.1, NZ_STEB01000030.1 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
1S1M | X-ray | 2.30 | A/B | 1-545 | [»] | |
2AD5 | X-ray | 2.80 | A/B | 1-545 | [»] | |
5TKV | X-ray | 2.70 | A/B | 1-545 | [»] | |
5U05 | electron microscopy | 7.90 | A/B/C/D | 1-545 | [»] | |
5U3C | electron microscopy | 4.60 | A/B/C/D | 1-545 | [»] | |
5U6R | electron microscopy | 5.70 | A/B/C/D | 1-545 | [»] | |
SMRi | P0A7E5 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 4262298, 5 interactors |
DIPi | DIP-10628N |
IntActi | P0A7E5, 8 interactors |
STRINGi | 511145.b2780 |
Protein family/group databases
MEROPSi | C26.964 |
2D gel databases
SWISS-2DPAGEi | P0A7E5 |
Proteomic databases
jPOSTi | P0A7E5 |
PaxDbi | P0A7E5 |
PRIDEi | P0A7E5 |
Genome annotation databases
EnsemblBacteriai | AAC75822; AAC75822; b2780 BAE76854; BAE76854; BAE76854 |
GeneIDi | 58459987 946116 |
KEGGi | ecj:JW2751 eco:b2780 |
PATRICi | fig|1411691.4.peg.3955 |
Organism-specific databases
EchoBASEi | EB0803 |
Phylogenomic databases
eggNOGi | COG0504, Bacteria |
HOGENOMi | CLU_011675_5_0_6 |
InParanoidi | P0A7E5 |
PhylomeDBi | P0A7E5 |
Enzyme and pathway databases
UniPathwayi | UPA00159;UER00277 |
BioCyci | EcoCyc:CTPSYN-MONOMER MetaCyc:CTPSYN-MONOMER |
BRENDAi | 6.3.4.2, 2026 |
Miscellaneous databases
EvolutionaryTracei | P0A7E5 |
PROi | PR:P0A7E5 |
Family and domain databases
CDDi | cd03113, CTPS_N, 1 hit cd01746, GATase1_CTP_Synthase, 1 hit |
Gene3Di | 3.40.50.880, 1 hit |
HAMAPi | MF_01227, PyrG, 1 hit |
InterProi | View protein in InterPro IPR029062, Class_I_gatase-like IPR004468, CTP_synthase IPR017456, CTP_synthase_N IPR017926, GATASE IPR033828, GATase1_CTP_Synthase IPR027417, P-loop_NTPase |
PANTHERi | PTHR11550, PTHR11550, 1 hit |
Pfami | View protein in Pfam PF06418, CTP_synth_N, 1 hit PF00117, GATase, 1 hit |
SUPFAMi | SSF52317, SSF52317, 1 hit SSF52540, SSF52540, 1 hit |
TIGRFAMsi | TIGR00337, PyrG, 1 hit |
PROSITEi | View protein in PROSITE PS51273, GATASE_TYPE_1, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | PYRG_ECOLI | |
Accessioni | P0A7E5Primary (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: | April 7, 2021 | |
This is version 136 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Prokaryotic Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
3D-structure, Direct protein sequencing, Reference proteomeDocuments
- PATHWAY comments
Index of metabolic and biosynthesis pathways - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families