ID   A0A4R5DWF2_9ACTN        Unreviewed;       564 AA.
AC   A0A4R5DWF2;
DT   31-JUL-2019, integrated into UniProtKB/TrEMBL.
DT   31-JUL-2019, sequence version 1.
DT   13-NOV-2019, entry version 4.
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   ORFNames=E1289_36460 {ECO:0000313|EMBL:TDE16944.1};
OS   Actinomadura sp. 6K520.
OC   Bacteria; Actinobacteria; Streptosporangiales; Thermomonosporaceae;
OC   Actinomadura; unclassified Actinomadura.
OX   NCBI_TaxID=2530364 {ECO:0000313|EMBL:TDE16944.1, ECO:0000313|Proteomes:UP000295189};
RN   [1] {ECO:0000313|EMBL:TDE16944.1, ECO:0000313|Proteomes:UP000295189}
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=6K520 {ECO:0000313|EMBL:TDE16944.1,
RC   ECO:0000313|Proteomes:UP000295189};
RA   Sahin N., Ay H., Saygin H.;
RT   "Draft genome sequences of novel Actinobacteria.";
RL   Submitted (MAR-2019) to the EMBL/GenBank/DDBJ databases.
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:46398,
CC         ChEBI:CHEBI:58359, ChEBI:CHEBI:456216; EC=6.3.4.2;
CC         Evidence={ECO:0000256|HAMAP-Rule:MF_01227,
CC         ECO:0000256|SAAS:SAAS01116648};
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}.
CC   -!- CAUTION: The sequence shown here is derived from an
CC       EMBL/GenBank/DDBJ whole genome shotgun (WGS) entry which is
CC       preliminary data. {ECO:0000313|EMBL:TDE16944.1}.
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DR   EMBL; SMLC01000309; TDE16944.1; -; Genomic_DNA.
DR   UniPathway; UPA00159; UER00277.
DR   Proteomes; UP000295189; Unassembled WGS sequence.
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:UP000295189};
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:TDE16944.1};
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      302    551       Glutamine amidotransferase type-1.
FT                                {ECO:0000259|PROSITE:PS51273}.
FT   NP_BIND      24     29       ATP. {ECO:0000256|HAMAP-Rule:MF_01227}.
FT   NP_BIND     158    160       Allosteric inhibitor CTP.
FT                                {ECO:0000256|HAMAP-Rule:MF_01227}.
FT   NP_BIND     198    203       Allosteric inhibitor CTP; alternate.
FT                                {ECO:0000256|HAMAP-Rule:MF_01227}.
FT   NP_BIND     198    203       UTP; alternate. {ECO:0000256|HAMAP-Rule:
FT                                MF_01227}.
FT   REGION        1    277       Amidoligase domain. {ECO:0000256|HAMAP-
FT                                Rule:MF_01227}.
FT   REGION      393    396       L-glutamine binding. {ECO:0000256|HAMAP-
FT                                Rule:MF_01227}.
FT   ACT_SITE    392    392       Nucleophile. {ECO:0000256|PROSITE-
FT                                ProRule:PRU00605}.
FT   ACT_SITE    392    392       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        81     81       Magnesium. {ECO:0000256|HAMAP-Rule:
FT                                MF_01227}.
FT   METAL       151    151       Magnesium. {ECO:0000256|HAMAP-Rule:
FT                                MF_01227}.
FT   BINDING      23     23       Allosteric inhibitor CTP; alternate.
FT                                {ECO:0000256|HAMAP-Rule:MF_01227}.
FT   BINDING      23     23       UTP; alternate. {ECO:0000256|HAMAP-Rule:
FT                                MF_01227}.
FT   BINDING      81     81       ATP. {ECO:0000256|HAMAP-Rule:MF_01227}.
FT   BINDING     234    234       Allosteric inhibitor CTP; alternate.
FT                                {ECO:0000256|HAMAP-Rule:MF_01227}.
FT   BINDING     234    234       UTP; alternate. {ECO:0000256|HAMAP-Rule:
FT                                MF_01227}.
FT   BINDING     252    252       ATP. {ECO:0000256|HAMAP-Rule:MF_01227}.
FT   BINDING     365    365       L-glutamine; via carbonyl oxygen.
FT                                {ECO:0000256|HAMAP-Rule:MF_01227}.
FT   BINDING     416    416       L-glutamine. {ECO:0000256|HAMAP-Rule:
FT                                MF_01227}.
FT   BINDING     477    477       L-glutamine; via amide nitrogen.
FT                                {ECO:0000256|HAMAP-Rule:MF_01227}.
SQ   SEQUENCE   564 AA;  61419 MW;  DBCF46F85919B078 CRC64;
     MPSAATGSSR PTKHLFVTGG VASSLGKGLT ASSLGRLLTL RGLRVTMQKL DPYLNVDPGT
     MNPFQHGEVF VTDDGAETDL DIGHYERFLD TELHGSANVT TGQVYSNVIA KERRGEYLGD
     TVQVIPHITN EIKDRIIGMA ADDDVDIVIT EVGGTVGDIE SLPFLEAVRQ IRHEIGRDNC
     FFLHVSLLPY IGPSGELKTK PTQHSVAALR SIGIQPDAIV CRSDRPITDG LKHKISLMCD
     VDREAVVSAV DAASIYDIPK VLHSEGLDAY VVRRLDLPFR DVDWGAWDEL LRRVHKPARE
     VTIALVGKYI DLPDAYLSVT EALRHGGFGN DAKVHIRWVK SDDCETAEGA KRELDGVDGV
     LIPGGFGVRG IEGKLGAVRH ARENRVPLLG ICLGLQCMVI EAARTLAGLA GADSAEFDAT
     TAHPVVATMT DQVDVVAGER DMGGTMRLGL YPADLAEGSI VRELYGEAKV SERHRHRYEV
     SNVYRDRLEE AGLWFSGLSP DGRLVEYVEL PRDRHPFFVG TQAHPEFRSR PTRPHPLFTG
     LVTAALDYAE ARTGDGEAGN VTVS
//