ID   A0A2Z5JWN4_9ACTN        Unreviewed;       552 AA.
AC   A0A2Z5JWN4;
DT   10-OCT-2018, integrated into UniProtKB/TrEMBL.
DT   10-OCT-2018, sequence version 1.
DT   05-DEC-2018, entry version 3.
DE   RecName: Full=CTP synthase {ECO:0000256|HAMAP-Rule:MF_01227};
DE            EC=6.3.4.2 {ECO:0000256|HAMAP-Rule:MF_01227};
DE   AltName: Full=Cytidine 5'-triphosphate synthase {ECO:0000256|HAMAP-Rule:MF_01227};
DE   AltName: Full=Cytidine triphosphate synthetase {ECO:0000256|HAMAP-Rule:MF_01227};
DE            Short=CTP synthetase {ECO:0000256|HAMAP-Rule:MF_01227};
DE            Short=CTPS {ECO:0000256|HAMAP-Rule:MF_01227};
DE   AltName: Full=UTP--ammonia ligase {ECO:0000256|HAMAP-Rule:MF_01227};
GN   Name=pyrG {ECO:0000256|HAMAP-Rule:MF_01227,
GN   ECO:0000313|EMBL:AXE84861.1};
GN   ORFNames=C1703_07625 {ECO:0000313|EMBL:AXE84861.1};
OS   Streptomyces sp. Go-475.
OC   Bacteria; Actinobacteria; Streptomycetales; Streptomycetaceae;
OC   Streptomyces.
OX   NCBI_TaxID=2072505 {ECO:0000313|EMBL:AXE84861.1, ECO:0000313|Proteomes:UP000253251};
RN   [1] {ECO:0000313|EMBL:AXE84861.1, ECO:0000313|Proteomes:UP000253251}
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Go-475 {ECO:0000313|EMBL:AXE84861.1,
RC   ECO:0000313|Proteomes:UP000253251};
RX   PubMed=29946312; DOI=.3389/fmicb.2018.01270;
RA   Kibret M., Guerrero-Garzon J.F., Urban E., Zehl M., Wronski V.K.,
RA   Ruckert C., Busche T., Kalinowski J., Rollinger J.M., Abate D.,
RA   Zotchev S.B.;
RT   "Streptomyces spp. From Ethiopia Producing Antimicrobial Compounds:
RT   Characterization via Bioassays, Genome Analyses, and Mass
RT   Spectrometry.";
RL   Front. Microbiol. 9:1270-1270(2018).
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:0000256|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:456216,
CC         ChEBI:CHEBI:46398, ChEBI:CHEBI:58359; EC=6.3.4.2;
CC         Evidence={ECO:0000256|HAMAP-Rule:MF_01227,
CC         ECO:0000256|SAAS:SAAS00710710};
CC   -!- ACTIVITY REGULATION: Allosterically activated by GTP, when
CC       glutamine is the substrate; GTP has no effect on the reaction when
CC       ammonia is the substrate. The allosteric effector GTP functions by
CC       stabilizing the protein conformation that binds the tetrahedral
CC       intermediate(s) formed during glutamine hydrolysis. Inhibited by
CC       the product CTP, via allosteric rather than competitive
CC       inhibition. {ECO:0000256|HAMAP-Rule:MF_01227}.
CC   -!- PATHWAY: Pyrimidine metabolism; CTP biosynthesis via de novo
CC       pathway; CTP from UDP: step 2/2. {ECO:0000256|HAMAP-Rule:MF_01227,
CC       ECO:0000256|SAAS:SAAS00710815}.
CC   -!- SUBUNIT: Homotetramer. {ECO:0000256|HAMAP-Rule:MF_01227,
CC       ECO:0000256|SAAS:SAAS00710816}.
CC   -!- MISCELLANEOUS: CTPSs have evolved a hybrid strategy for
CC       distinguishing between UTP and CTP. The overlapping regions of the
CC       product feedback inhibitory and substrate sites recognize a common
CC       feature in both compounds, the triphosphate moiety. To
CC       differentiate isosteric substrate and product pyrimidine rings, an
CC       additional pocket far from the expected kinase/ligase catalytic
CC       site, specifically recognizes the cytosine and ribose portions of
CC       the product inhibitor. {ECO:0000256|HAMAP-Rule:MF_01227}.
CC   -!- SIMILARITY: Belongs to the CTP synthase family.
CC       {ECO:0000256|HAMAP-Rule:MF_01227, ECO:0000256|SAAS:SAAS00710794}.
CC   -!- CAUTION: Lacks conserved residue(s) required for the propagation
CC       of feature annotation. {ECO:0000256|HAMAP-Rule:MF_01227}.
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DR   EMBL; CP026121; AXE84861.1; -; Genomic_DNA.
DR   UniPathway; UPA00159; UER00277.
DR   Proteomes; UP000253251; 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: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-UniRule.
DR   CDD; cd01746; GATase1_CTP_Synthase; 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 {ECO:0000256|HAMAP-Rule:MF_01227,
KW   ECO:0000256|SAAS:SAAS00710699};
KW   Complete proteome {ECO:0000313|Proteomes:UP000253251};
KW   Glutamine amidotransferase {ECO:0000256|HAMAP-Rule:MF_01227,
KW   ECO:0000256|PROSITE-ProRule:PRU00605, ECO:0000256|SAAS:SAAS00710676};
KW   Ligase {ECO:0000256|HAMAP-Rule:MF_01227,
KW   ECO:0000256|SAAS:SAAS00710762, ECO:0000313|EMBL:AXE84861.1};
KW   Magnesium {ECO:0000256|HAMAP-Rule:MF_01227,
KW   ECO:0000256|SAAS:SAAS00710689};
KW   Metal-binding {ECO:0000256|HAMAP-Rule:MF_01227,
KW   ECO:0000256|SAAS:SAAS00710675};
KW   Nucleotide-binding {ECO:0000256|HAMAP-Rule:MF_01227,
KW   ECO:0000256|SAAS:SAAS00710810};
KW   Pyrimidine biosynthesis {ECO:0000256|HAMAP-Rule:MF_01227,
KW   ECO:0000256|SAAS:SAAS00710748}.
FT   DOMAIN      300    551       Glutamine amidotransferase type-1.
FT                                {ECO:0000259|PROSITE:PS51273}.
FT   NP_BIND      23     28       ATP. {ECO:0000256|HAMAP-Rule:MF_01227}.
FT   NP_BIND     156    158       Allosteric inhibitor CTP.
FT                                {ECO:0000256|HAMAP-Rule:MF_01227}.
FT   NP_BIND     196    201       Allosteric inhibitor CTP; alternate.
FT                                {ECO:0000256|HAMAP-Rule:MF_01227}.
FT   NP_BIND     196    201       UTP; alternate. {ECO:0000256|HAMAP-Rule:
FT                                MF_01227}.
FT   REGION        1    275       Amidoligase domain. {ECO:0000256|HAMAP-
FT                                Rule:MF_01227}.
FT   REGION      391    394       L-glutamine binding. {ECO:0000256|HAMAP-
FT                                Rule:MF_01227}.
FT   ACT_SITE    390    390       Nucleophile. {ECO:0000256|PROSITE-
FT                                ProRule:PRU00605}.
FT   ACT_SITE    390    390       Nucleophile; for glutamine hydrolysis.
FT                                {ECO:0000256|HAMAP-Rule:MF_01227}.
FT   ACT_SITE    524    524       {ECO:0000256|HAMAP-Rule:MF_01227,
FT                                ECO:0000256|PROSITE-ProRule:PRU00605}.
FT   ACT_SITE    526    526       {ECO:0000256|HAMAP-Rule:MF_01227,
FT                                ECO:0000256|PROSITE-ProRule:PRU00605}.
FT   METAL        80     80       Magnesium. {ECO:0000256|HAMAP-Rule:
FT                                MF_01227}.
FT   METAL       149    149       Magnesium. {ECO:0000256|HAMAP-Rule:
FT                                MF_01227}.
FT   BINDING      22     22       Allosteric inhibitor CTP; alternate.
FT                                {ECO:0000256|HAMAP-Rule:MF_01227}.
FT   BINDING      22     22       UTP; alternate. {ECO:0000256|HAMAP-Rule:
FT                                MF_01227}.
FT   BINDING      80     80       ATP. {ECO:0000256|HAMAP-Rule:MF_01227}.
FT   BINDING     232    232       Allosteric inhibitor CTP; alternate.
FT                                {ECO:0000256|HAMAP-Rule:MF_01227}.
FT   BINDING     232    232       UTP; alternate. {ECO:0000256|HAMAP-Rule:
FT                                MF_01227}.
FT   BINDING     250    250       ATP. {ECO:0000256|HAMAP-Rule:MF_01227}.
FT   BINDING     363    363       L-glutamine; via carbonyl oxygen.
FT                                {ECO:0000256|HAMAP-Rule:MF_01227}.
FT   BINDING     414    414       L-glutamine. {ECO:0000256|HAMAP-Rule:
FT                                MF_01227}.
FT   BINDING     476    476       L-glutamine; via amide nitrogen.
FT                                {ECO:0000256|HAMAP-Rule:MF_01227}.
SQ   SEQUENCE   552 AA;  60457 MW;  57320F900530D6D6 CRC64;
     MPPAAFRNST TKHIFVTGGV ASSLGKGLTA SSLGMLLKAR GLRVVMQKLD PYLNVDPGTM
     NPFQHGEVFV TNDGAETDLD IGHYERFLDR DLDGSANVTT GQVYSTVIAK ERRGEYLGDT
     VQVIPHITNE IKHRIRRMAT DEVDVVITEV GGTVGDIESL PFLETVRQVR HEVGRDNVFV
     VHISLLPYIG PSGELKTKPT QHSVAALRNI GIQPDAIVLR CDREVPTAIK RKISLMCDVD
     EAAVVACPDA RSIYDIPKTV HGEGLDAYVV RKLDLPFRDV DWTTWDDLLD RVHNPDHEVT
     LALVGKYIDL PDAYLSVTEA LRAGGFANRA RVKIKWVTSD DCKTPAGAAA QLGDVDGICI
     PGGFGDRGVL GKVGAIKYAR ENKIPLLGLC LGLQCIVIEA ARNLADISDA NSTEFDPATA
     HPVISTMAEQ LDIVAGEGDM GGTMRLGMYP AKLAEGSIVR EVYDGKEYVE ERHRHRYEVN
     NAYRAELEKR AGILFSGTSP DGKLVEYVEY PRDVHPYLVA TQAHPELRSR PTRPHPLFAG
     LVKAAVERKT SK
//