PYRG_SACS2
ID PYRG_SACS2 Reviewed; 535 AA.
AC Q980S6;
DT 19-OCT-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2001, sequence version 1.
DT 03-AUG-2022, entry version 118.
DE RecName: Full=CTP synthase {ECO:0000255|HAMAP-Rule:MF_01227, ECO:0000303|PubMed:21301086};
DE EC=6.3.4.2 {ECO:0000255|HAMAP-Rule:MF_01227, ECO:0000269|PubMed:21301086};
DE AltName: Full=Cytidine 5'-triphosphate synthase {ECO:0000255|HAMAP-Rule:MF_01227};
DE AltName: Full=Cytidine triphosphate synthetase {ECO:0000255|HAMAP-Rule:MF_01227};
DE Short=CTP synthetase {ECO:0000255|HAMAP-Rule:MF_01227};
DE Short=CTPS {ECO:0000255|HAMAP-Rule:MF_01227};
DE AltName: Full=UTP--ammonia ligase {ECO:0000255|HAMAP-Rule:MF_01227};
GN Name=pyrG {ECO:0000255|HAMAP-Rule:MF_01227}; OrderedLocusNames=SSO0201;
OS Saccharolobus solfataricus (strain ATCC 35092 / DSM 1617 / JCM 11322 / P2)
OS (Sulfolobus solfataricus).
OC Archaea; Crenarchaeota; Thermoprotei; Sulfolobales; Sulfolobaceae;
OC Saccharolobus.
OX NCBI_TaxID=273057;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 35092 / DSM 1617 / JCM 11322 / P2;
RX PubMed=11427726; DOI=10.1073/pnas.141222098;
RA She Q., Singh R.K., Confalonieri F., Zivanovic Y., Allard G., Awayez M.J.,
RA Chan-Weiher C.C.-Y., Clausen I.G., Curtis B.A., De Moors A., Erauso G.,
RA Fletcher C., Gordon P.M.K., Heikamp-de Jong I., Jeffries A.C., Kozera C.J.,
RA Medina N., Peng X., Thi-Ngoc H.P., Redder P., Schenk M.E., Theriault C.,
RA Tolstrup N., Charlebois R.L., Doolittle W.F., Duguet M., Gaasterland T.,
RA Garrett R.A., Ragan M.A., Sensen C.W., Van der Oost J.;
RT "The complete genome of the crenarchaeon Sulfolobus solfataricus P2.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:7835-7840(2001).
RN [2]
RP X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS), FUNCTION, CATALYTIC ACTIVITY, AND
RP SUBUNIT.
RC STRAIN=ATCC 35092 / DSM 1617 / JCM 11322 / P2;
RX PubMed=21301086; DOI=10.1107/s1744309110052334;
RA Lauritsen I., Willemoes M., Jensen K.F., Johansson E., Harris P.;
RT "Structure of the dimeric form of CTP synthase from Sulfolobus
RT solfataricus.";
RL Acta Crystallogr. F 67:201-208(2011).
CC -!- FUNCTION: Catalyzes the ATP-dependent amination of UTP to CTP with
CC either L-glutamine or ammonia as the source of nitrogen
CC (PubMed:21301086). Regulates intracellular CTP levels through
CC interactions with the four ribonucleotide triphosphates (By
CC similarity). {ECO:0000255|HAMAP-Rule:MF_01227,
CC ECO:0000269|PubMed:21301086}.
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:0000255|HAMAP-Rule:MF_01227,
CC ECO:0000269|PubMed:21301086};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + L-glutamine = L-glutamate + NH4(+);
CC Xref=Rhea:RHEA:15889, ChEBI:CHEBI:15377, ChEBI:CHEBI:28938,
CC ChEBI:CHEBI:29985, ChEBI:CHEBI:58359; Evidence={ECO:0000255|HAMAP-
CC Rule:MF_01227};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + NH4(+) + UTP = ADP + CTP + 2 H(+) + phosphate;
CC Xref=Rhea:RHEA:16597, ChEBI:CHEBI:15378, ChEBI:CHEBI:28938,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:37563, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:46398, ChEBI:CHEBI:456216; Evidence={ECO:0000255|HAMAP-
CC Rule:MF_01227};
CC -!- ACTIVITY REGULATION: Allosterically activated by GTP, when glutamine is
CC the substrate; GTP has no effect on the reaction when ammonia is the
CC substrate. The allosteric effector GTP functions by stabilizing the
CC protein conformation that binds the tetrahedral intermediate(s) formed
CC during glutamine hydrolysis. Inhibited by the product CTP, via
CC allosteric rather than competitive inhibition. {ECO:0000255|HAMAP-
CC Rule:MF_01227}.
CC -!- PATHWAY: Pyrimidine metabolism; CTP biosynthesis via de novo pathway;
CC CTP from UDP: step 2/2. {ECO:0000255|HAMAP-Rule:MF_01227}.
CC -!- SUBUNIT: Homotetramer in the presence of ATP and UTP. The enzyme
CC dissociates into homodimers in the absence of substrate nucleotides.
CC {ECO:0000269|PubMed:21301086}.
CC -!- MISCELLANEOUS: CTPSs have evolved a hybrid strategy for distinguishing
CC between UTP and CTP. The overlapping regions of the product feedback
CC inhibitory and substrate sites recognize a common feature in both
CC compounds, the triphosphate moiety. To differentiate isosteric
CC substrate and product pyrimidine rings, an additional pocket far from
CC the expected kinase/ligase catalytic site, specifically recognizes the
CC cytosine and ribose portions of the product inhibitor.
CC {ECO:0000255|HAMAP-Rule:MF_01227}.
CC -!- SIMILARITY: Belongs to the CTP synthase family. {ECO:0000255|HAMAP-
CC Rule:MF_01227}.
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DR EMBL; AE006641; AAK40547.1; -; Genomic_DNA.
DR PIR; D90161; D90161.
DR RefSeq; WP_009990444.1; NC_002754.1.
DR PDB; 3NVA; X-ray; 2.50 A; A/B=1-535.
DR PDBsum; 3NVA; -.
DR AlphaFoldDB; Q980S6; -.
DR SMR; Q980S6; -.
DR STRING; 273057.SSO0201; -.
DR EnsemblBacteria; AAK40547; AAK40547; SSO0201.
DR GeneID; 44129171; -.
DR KEGG; sso:SSO0201; -.
DR PATRIC; fig|273057.12.peg.201; -.
DR eggNOG; arCOG00063; Archaea.
DR HOGENOM; CLU_011675_5_0_2; -.
DR InParanoid; Q980S6; -.
DR OMA; EFNNAYR; -.
DR PhylomeDB; Q980S6; -.
DR BRENDA; 6.3.4.2; 6163.
DR UniPathway; UPA00159; UER00277.
DR EvolutionaryTrace; Q980S6; -.
DR Proteomes; UP000001974; Chromosome.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0003883; F:CTP synthase activity; IBA:GO_Central.
DR GO; GO:0004359; F:glutaminase activity; IEA:RHEA.
DR GO; GO:0042802; F:identical protein binding; IBA:GO_Central.
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:0006241; P:CTP biosynthetic process; IBA:GO_Central.
DR GO; GO:0006541; P:glutamine metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0019856; P:pyrimidine nucleobase biosynthetic process; IBA:GO_Central.
DR CDD; cd03113; CTPS_N; 1.
DR CDD; cd01746; GATase1_CTP_Synthase; 1.
DR Gene3D; 3.40.50.300; -; 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 1: Evidence at protein level;
KW 3D-structure; ATP-binding; Glutamine amidotransferase; Ligase; Magnesium;
KW Metal-binding; Nucleotide-binding; Pyrimidine biosynthesis;
KW Reference proteome.
FT CHAIN 1..535
FT /note="CTP synthase"
FT /id="PRO_0000138270"
FT DOMAIN 302..535
FT /note="Glutamine amidotransferase type-1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT REGION 1..268
FT /note="Amidoligase domain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT ACT_SITE 386
FT /note="Nucleophile; for glutamine hydrolysis"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT ACT_SITE 511
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT ACT_SITE 513
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 14
FT /ligand="CTP"
FT /ligand_id="ChEBI:CHEBI:37563"
FT /ligand_note="allosteric inhibitor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 14
FT /ligand="UTP"
FT /ligand_id="ChEBI:CHEBI:46398"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 15..20
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 55
FT /ligand="L-glutamine"
FT /ligand_id="ChEBI:CHEBI:58359"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 72
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 72
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 142
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 149..151
FT /ligand="CTP"
FT /ligand_id="ChEBI:CHEBI:37563"
FT /ligand_note="allosteric inhibitor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 189..194
FT /ligand="CTP"
FT /ligand_id="ChEBI:CHEBI:37563"
FT /ligand_note="allosteric inhibitor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 189..194
FT /ligand="UTP"
FT /ligand_id="ChEBI:CHEBI:46398"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 225
FT /ligand="CTP"
FT /ligand_id="ChEBI:CHEBI:37563"
FT /ligand_note="allosteric inhibitor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 225
FT /ligand="UTP"
FT /ligand_id="ChEBI:CHEBI:46398"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 243
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 359
FT /ligand="L-glutamine"
FT /ligand_id="ChEBI:CHEBI:58359"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 387..390
FT /ligand="L-glutamine"
FT /ligand_id="ChEBI:CHEBI:58359"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 410
FT /ligand="L-glutamine"
FT /ligand_id="ChEBI:CHEBI:58359"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 467
FT /ligand="L-glutamine"
FT /ligand_id="ChEBI:CHEBI:58359"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT STRAND 4..9
FT /evidence="ECO:0007829|PDB:3NVA"
FT TURN 14..17
FT /evidence="ECO:0007829|PDB:3NVA"
FT HELIX 18..31
FT /evidence="ECO:0007829|PDB:3NVA"
FT STRAND 36..42
FT /evidence="ECO:0007829|PDB:3NVA"
FT STRAND 44..49
FT /evidence="ECO:0007829|PDB:3NVA"
FT HELIX 54..57
FT /evidence="ECO:0007829|PDB:3NVA"
FT HELIX 72..80
FT /evidence="ECO:0007829|PDB:3NVA"
FT HELIX 86..88
FT /evidence="ECO:0007829|PDB:3NVA"
FT STRAND 89..91
FT /evidence="ECO:0007829|PDB:3NVA"
FT HELIX 92..104
FT /evidence="ECO:0007829|PDB:3NVA"
FT TURN 105..110
FT /evidence="ECO:0007829|PDB:3NVA"
FT HELIX 115..134
FT /evidence="ECO:0007829|PDB:3NVA"
FT STRAND 137..143
FT /evidence="ECO:0007829|PDB:3NVA"
FT HELIX 150..152
FT /evidence="ECO:0007829|PDB:3NVA"
FT HELIX 153..166
FT /evidence="ECO:0007829|PDB:3NVA"
FT TURN 168..170
FT /evidence="ECO:0007829|PDB:3NVA"
FT STRAND 171..178
FT /evidence="ECO:0007829|PDB:3NVA"
FT TURN 183..185
FT /evidence="ECO:0007829|PDB:3NVA"
FT STRAND 186..188
FT /evidence="ECO:0007829|PDB:3NVA"
FT HELIX 191..203
FT /evidence="ECO:0007829|PDB:3NVA"
FT STRAND 208..216
FT /evidence="ECO:0007829|PDB:3NVA"
FT HELIX 220..229
FT /evidence="ECO:0007829|PDB:3NVA"
FT HELIX 234..236
FT /evidence="ECO:0007829|PDB:3NVA"
FT STRAND 237..241
FT /evidence="ECO:0007829|PDB:3NVA"
FT HELIX 246..248
FT /evidence="ECO:0007829|PDB:3NVA"
FT HELIX 249..256
FT /evidence="ECO:0007829|PDB:3NVA"
FT HELIX 258..265
FT /evidence="ECO:0007829|PDB:3NVA"
FT HELIX 276..286
FT /evidence="ECO:0007829|PDB:3NVA"
FT TURN 287..289
FT /evidence="ECO:0007829|PDB:3NVA"
FT STRAND 293..301
FT /evidence="ECO:0007829|PDB:3NVA"
FT HELIX 306..309
FT /evidence="ECO:0007829|PDB:3NVA"
FT HELIX 310..322
FT /evidence="ECO:0007829|PDB:3NVA"
FT STRAND 326..333
FT /evidence="ECO:0007829|PDB:3NVA"
FT HELIX 334..337
FT /evidence="ECO:0007829|PDB:3NVA"
FT STRAND 340..342
FT /evidence="ECO:0007829|PDB:3NVA"
FT TURN 345..349
FT /evidence="ECO:0007829|PDB:3NVA"
FT STRAND 352..356
FT /evidence="ECO:0007829|PDB:3NVA"
FT HELIX 365..378
FT /evidence="ECO:0007829|PDB:3NVA"
FT STRAND 382..385
FT /evidence="ECO:0007829|PDB:3NVA"
FT HELIX 387..398
FT /evidence="ECO:0007829|PDB:3NVA"
FT TURN 399..401
FT /evidence="ECO:0007829|PDB:3NVA"
FT TURN 409..411
FT /evidence="ECO:0007829|PDB:3NVA"
FT STRAND 418..421
FT /evidence="ECO:0007829|PDB:3NVA"
FT STRAND 425..427
FT /evidence="ECO:0007829|PDB:3NVA"
FT STRAND 437..445
FT /evidence="ECO:0007829|PDB:3NVA"
FT HELIX 450..455
FT /evidence="ECO:0007829|PDB:3NVA"
FT STRAND 457..466
FT /evidence="ECO:0007829|PDB:3NVA"
FT HELIX 472..480
FT /evidence="ECO:0007829|PDB:3NVA"
FT STRAND 484..488
FT /evidence="ECO:0007829|PDB:3NVA"
FT STRAND 494..498
FT /evidence="ECO:0007829|PDB:3NVA"
FT STRAND 505..510
FT /evidence="ECO:0007829|PDB:3NVA"
FT HELIX 512..515
FT /evidence="ECO:0007829|PDB:3NVA"
FT STRAND 518..520
FT /evidence="ECO:0007829|PDB:3NVA"
FT HELIX 523..532
FT /evidence="ECO:0007829|PDB:3NVA"
SQ SEQUENCE 535 AA; 59760 MW; C4E4BDE58B3DADED CRC64;
MPNKYIVVTG GVLSSVGKGT LVASIGMLLK RRGYNVTAVK IDPYINVDAG TMNPYMHGEV
FVTEDGAETD LDLGHYERFM DVNMTKYNNI TAGKVYFEVI KKEREGKYLG QTVQIIPHVT
DQIKDMIRYA SKINNAEITL VEIGGTVGDI ESLPFLEAVR QLKLEEGEDN VIFVHIALVE
YLSVTGELKT KPLQHSVQEL RRIGIQPDFI VGRATLPLDD ETRRKIALFT NVKVDHIVSS
YDVETSYEVP IILESQKLVS KILSRLKLED RQVDLTDWIS FVNNIKGINS KKTINIALVG
KYTKLKDSYI SIKEAIYHAS AYIGVRPKLI WIESTDLESD TKNLNEILGN VNGIIVLPGF
GSRGAEGKIK AIKYAREHNI PFLGICFGFQ LSIVEFARDV LGLSEANSTE INPNTKDPVI
TLLDEQKNVT QLGGTMRLGA QKIILKEGTI AYQLYGKKVV YERHRHRYEV NPKYVDILED
AGLVVSGISE NGLVEIIELP SNKFFVATQA HPEFKSRPTN PSPIYLGFIR AVASL
