UPP_TOXGO
ID UPP_TOXGO Reviewed; 244 AA.
AC Q26998;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 107.
DE RecName: Full=Uracil phosphoribosyltransferase;
DE Short=UPRT;
DE Short=UPRTase;
DE EC=2.4.2.9 {ECO:0000269|PubMed:11773618, ECO:0000269|PubMed:9247925};
DE AltName: Full=UMP pyrophosphorylase;
GN Name=uprt;
OS Toxoplasma gondii.
OC Eukaryota; Sar; Alveolata; Apicomplexa; Conoidasida; Coccidia;
OC Eucoccidiorida; Eimeriorina; Sarcocystidae; Toxoplasma.
OX NCBI_TaxID=5811;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROTEIN SEQUENCE OF 2-6, FUNCTION,
RP SUBUNIT, BIOPHYSICOCHEMICAL PROPERTIES, AND CATALYTIC ACTIVITY.
RC STRAIN=RH / EP;
RX PubMed=9247925; DOI=10.1016/s0166-6851(97)00058-3;
RA Carter D., Donald R.G.K., Roos D., Ullman B.;
RT "Expression, purification, and characterization of uracil
RT phosphoribosyltransferase from Toxoplasma gondii.";
RL Mol. Biochem. Parasitol. 87:137-144(1997).
RN [2]
RP X-RAY CRYSTALLOGRAPHY (1.93 ANGSTROMS) OF MUTANT VAL-128 APOENZYME AND IN
RP COMPLEXES WITH SUBSTRATES AND 5-FLUOROURACIL, AND MUTAGENESIS OF CYS-128.
RX PubMed=9628859; DOI=10.1093/emboj/17.12.3219;
RA Schumacher M.A., Carter D., Scott D.M., Roos D.S., Ullman B., Brennan R.G.;
RT "Crystal structures of Toxoplasma gondii uracil phosphoribosyltransferase
RT reveal the atomic basis of pyrimidine discrimination and prodrug binding.";
RL EMBO J. 17:3219-3232(1998).
RN [3]
RP X-RAY CRYSTALLOGRAPHY (2.45 ANGSTROMS) OF MUTANT VAL-128 IN COMPLEXES WITH
RP URACIL; SUBSTRATE ANALOG AND GTP, COFACTOR, SUBUNIT, BIOPHYSICOCHEMICAL
RP PROPERTIES, ACTIVITY REGULATION, MUTAGENESIS OF LYS-59; ARG-68; LYS-150 AND
RP ASP-235, AND CATALYTIC ACTIVITY.
RX PubMed=11773618; DOI=10.1073/pnas.012399599;
RA Schumacher M.A., Bashor C.J., Song M.H., Otsu K., Zhu S., Parry R.J.,
RA Ullman B., Brennan R.G.;
RT "The structural mechanism of GTP stabilized oligomerization and catalytic
RT activation of the Toxoplasma gondii uracil phosphoribosyltransferase.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:78-83(2002).
CC -!- FUNCTION: Catalyzes the conversion of uracil and 5-phospho-alpha-D-
CC ribose 1-diphosphate (PRPP) to UMP and diphosphate.
CC {ECO:0000269|PubMed:9247925}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=diphosphate + UMP = 5-phospho-alpha-D-ribose 1-diphosphate +
CC uracil; Xref=Rhea:RHEA:13017, ChEBI:CHEBI:17568, ChEBI:CHEBI:33019,
CC ChEBI:CHEBI:57865, ChEBI:CHEBI:58017; EC=2.4.2.9;
CC Evidence={ECO:0000269|PubMed:11773618, ECO:0000269|PubMed:9247925};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:11773618};
CC Note=Binds 1 Mg(2+) ion per subunit. The magnesium is bound as Mg-PRPP.
CC {ECO:0000269|PubMed:11773618};
CC -!- ACTIVITY REGULATION: Allosterically activated by GTP. Binding of GTP
CC leads to 5-time activation of the enzyme.
CC {ECO:0000269|PubMed:11773618}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=3.5 uM for uracil {ECO:0000269|PubMed:11773618,
CC ECO:0000269|PubMed:9247925};
CC KM=216 uM for 5-phospho-alpha-D-ribose 1-diphosphate (in the absence
CC of GTP) {ECO:0000269|PubMed:11773618, ECO:0000269|PubMed:9247925};
CC KM=37.4 uM for 5-phospho-alpha-D-ribose 1-diphosphate (in the
CC presence of GTP) {ECO:0000269|PubMed:11773618,
CC ECO:0000269|PubMed:9247925};
CC Vmax=0.45 umol/min/mg enzyme {ECO:0000269|PubMed:11773618,
CC ECO:0000269|PubMed:9247925};
CC -!- PATHWAY: Pyrimidine metabolism; UMP biosynthesis via salvage pathway;
CC UMP from uracil: step 1/1.
CC -!- SUBUNIT: Monomer. Forms homodimers in presence of substrates and
CC homotetramers in the presence of GTP. {ECO:0000269|PubMed:11773618,
CC ECO:0000269|PubMed:9247925}.
CC -!- SIMILARITY: Belongs to the UPRTase family. {ECO:0000305}.
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DR EMBL; U10246; AAB60213.1; -; Genomic_DNA.
DR PDB; 1BD3; X-ray; 1.93 A; A/B/C/D=2-244.
DR PDB; 1BD4; X-ray; 2.20 A; A/B/C/D=2-244.
DR PDB; 1JLR; X-ray; 2.45 A; A/B/C/D=2-244.
DR PDB; 1JLS; X-ray; 2.50 A; A/B/C/D=2-244.
DR PDB; 1UPF; X-ray; 2.30 A; A/B/C/D=21-244.
DR PDB; 1UPU; X-ray; 2.50 A; A/B/C/D=21-244.
DR PDBsum; 1BD3; -.
DR PDBsum; 1BD4; -.
DR PDBsum; 1JLR; -.
DR PDBsum; 1JLS; -.
DR PDBsum; 1UPF; -.
DR PDBsum; 1UPU; -.
DR AlphaFoldDB; Q26998; -.
DR SMR; Q26998; -.
DR EnsemblProtists; TGME49_312480-t26_1; TGME49_312480-t26_1; TGME49_312480.
DR VEuPathDB; ToxoDB:TGARI_312480; -.
DR VEuPathDB; ToxoDB:TGCAST_312480; -.
DR VEuPathDB; ToxoDB:TGCOUG_312480; -.
DR VEuPathDB; ToxoDB:TGDOM2_312480; -.
DR VEuPathDB; ToxoDB:TGFOU_312480; -.
DR VEuPathDB; ToxoDB:TGGT1_312480; -.
DR VEuPathDB; ToxoDB:TGMAS_312480; -.
DR VEuPathDB; ToxoDB:TGME49_312480; -.
DR VEuPathDB; ToxoDB:TGP89_312480; -.
DR VEuPathDB; ToxoDB:TGPRC2_312480; -.
DR VEuPathDB; ToxoDB:TGRH88_051740; -.
DR VEuPathDB; ToxoDB:TGRUB_312480; -.
DR VEuPathDB; ToxoDB:TGVAND_312480; -.
DR VEuPathDB; ToxoDB:TGVEG_312480; -.
DR OMA; TYATRMP; -.
DR BRENDA; 2.4.2.9; 6411.
DR SABIO-RK; Q26998; -.
DR UniPathway; UPA00574; UER00636.
DR EvolutionaryTrace; Q26998; -.
DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW.
DR GO; GO:0004845; F:uracil phosphoribosyltransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0044206; P:UMP salvage; IEA:UniProtKB-UniPathway.
DR CDD; cd06223; PRTases_typeI; 1.
DR Gene3D; 3.40.50.2020; -; 1.
DR InterPro; IPR000836; PRibTrfase_dom.
DR InterPro; IPR029057; PRTase-like.
DR SUPFAM; SSF53271; SSF53271; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Allosteric enzyme; Direct protein sequencing;
KW Glycosyltransferase; GTP-binding; Nucleotide-binding; Transferase.
FT CHAIN 1..244
FT /note="Uracil phosphoribosyltransferase"
FT /id="PRO_0000120783"
FT BINDING 59
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000269|PubMed:9628859,
FT ECO:0007744|PDB:1BD3, ECO:0007744|PDB:1UPU"
FT BINDING 68
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000269|PubMed:11773618,
FT ECO:0007744|PDB:1JLR"
FT BINDING 102..105
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000269|PubMed:11773618,
FT ECO:0007744|PDB:1JLR"
FT BINDING 112
FT /ligand="5-phospho-alpha-D-ribose 1-diphosphate"
FT /ligand_id="ChEBI:CHEBI:58017"
FT /evidence="ECO:0000269|PubMed:11773618,
FT ECO:0007744|PDB:1JLS"
FT BINDING 129
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000269|PubMed:11773618,
FT ECO:0000269|PubMed:9628859, ECO:0007744|PDB:1BD3,
FT ECO:0007744|PDB:1BD4, ECO:0007744|PDB:1JLR,
FT ECO:0007744|PDB:1JLS, ECO:0007744|PDB:1UPU"
FT BINDING 137
FT /ligand="5-phospho-alpha-D-ribose 1-diphosphate"
FT /ligand_id="ChEBI:CHEBI:58017"
FT /evidence="ECO:0000269|PubMed:11773618,
FT ECO:0000269|PubMed:9628859, ECO:0007744|PDB:1BD3,
FT ECO:0007744|PDB:1BD4, ECO:0007744|PDB:1JLR,
FT ECO:0007744|PDB:1JLS, ECO:0007744|PDB:1UPU"
FT BINDING 158
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000269|PubMed:11773618,
FT ECO:0000269|PubMed:9628859, ECO:0007744|PDB:1BD3,
FT ECO:0007744|PDB:1BD4, ECO:0007744|PDB:1JLR,
FT ECO:0007744|PDB:1JLS, ECO:0007744|PDB:1UPU"
FT BINDING 164..172
FT /ligand="5-phospho-alpha-D-ribose 1-diphosphate"
FT /ligand_id="ChEBI:CHEBI:58017"
FT /evidence="ECO:0000269|PubMed:11773618,
FT ECO:0000269|PubMed:9628859, ECO:0007744|PDB:1BD3,
FT ECO:0007744|PDB:1BD4, ECO:0007744|PDB:1JLR,
FT ECO:0007744|PDB:1JLS"
FT BINDING 164
FT /ligand="5-phospho-alpha-D-ribose 1-diphosphate"
FT /ligand_id="ChEBI:CHEBI:58017"
FT /evidence="ECO:0000269|PubMed:11773618,
FT ECO:0000269|PubMed:9628859, ECO:0007744|PDB:1JLS,
FT ECO:0007744|PDB:1UPU"
FT BINDING 229
FT /ligand="uracil"
FT /ligand_id="ChEBI:CHEBI:17568"
FT /evidence="ECO:0000269|PubMed:9628859,
FT ECO:0007744|PDB:1UPU"
FT BINDING 234..236
FT /ligand="uracil"
FT /ligand_id="ChEBI:CHEBI:17568"
FT /evidence="ECO:0000269|PubMed:9628859,
FT ECO:0007744|PDB:1UPU"
FT BINDING 235
FT /ligand="5-phospho-alpha-D-ribose 1-diphosphate"
FT /ligand_id="ChEBI:CHEBI:58017"
FT /evidence="ECO:0000269|PubMed:11773618,
FT ECO:0007744|PDB:1JLR, ECO:0007744|PDB:1JLS"
FT MUTAGEN 59
FT /note="K->A: GTP-induced enzymatic activation is reduced 4-
FT fold."
FT /evidence="ECO:0000269|PubMed:11773618"
FT MUTAGEN 68
FT /note="R->A: GTP-induced enzymatic activation is reduced 2-
FT fold."
FT /evidence="ECO:0000269|PubMed:11773618"
FT MUTAGEN 128
FT /note="C->V: No effect on activity. Far less oxidation
FT sensitive than wild-type."
FT /evidence="ECO:0000269|PubMed:9628859"
FT MUTAGEN 150
FT /note="K->A: GTP-induced enzymatic activation is reduced 4-
FT fold."
FT /evidence="ECO:0000269|PubMed:11773618"
FT MUTAGEN 235
FT /note="D->A,N: No enzymatic activity."
FT /evidence="ECO:0000269|PubMed:11773618"
FT STRAND 14..16
FT /evidence="ECO:0007829|PDB:1JLR"
FT HELIX 22..32
FT /evidence="ECO:0007829|PDB:1BD3"
FT STRAND 36..38
FT /evidence="ECO:0007829|PDB:1BD3"
FT HELIX 43..53
FT /evidence="ECO:0007829|PDB:1BD3"
FT HELIX 59..78
FT /evidence="ECO:0007829|PDB:1BD3"
FT STRAND 83..89
FT /evidence="ECO:0007829|PDB:1BD3"
FT TURN 91..93
FT /evidence="ECO:0007829|PDB:1JLS"
FT STRAND 95..101
FT /evidence="ECO:0007829|PDB:1BD3"
FT STRAND 105..111
FT /evidence="ECO:0007829|PDB:1BD3"
FT TURN 112..114
FT /evidence="ECO:0007829|PDB:1BD3"
FT HELIX 115..124
FT /evidence="ECO:0007829|PDB:1BD3"
FT STRAND 130..137
FT /evidence="ECO:0007829|PDB:1BD3"
FT STRAND 139..141
FT /evidence="ECO:0007829|PDB:1BD3"
FT STRAND 144..150
FT /evidence="ECO:0007829|PDB:1BD3"
FT HELIX 155..157
FT /evidence="ECO:0007829|PDB:1BD3"
FT STRAND 158..163
FT /evidence="ECO:0007829|PDB:1BD3"
FT STRAND 165..169
FT /evidence="ECO:0007829|PDB:1BD3"
FT HELIX 171..183
FT /evidence="ECO:0007829|PDB:1BD3"
FT HELIX 187..189
FT /evidence="ECO:0007829|PDB:1BD3"
FT STRAND 190..197
FT /evidence="ECO:0007829|PDB:1BD3"
FT HELIX 199..208
FT /evidence="ECO:0007829|PDB:1BD3"
FT STRAND 212..219
FT /evidence="ECO:0007829|PDB:1BD3"
FT STRAND 221..223
FT /evidence="ECO:0007829|PDB:1BD3"
FT STRAND 229..231
FT /evidence="ECO:0007829|PDB:1BD3"
FT HELIX 236..241
FT /evidence="ECO:0007829|PDB:1BD3"
SQ SEQUENCE 244 AA; 27646 MW; 1810CC234B2CE60F CRC64;
MAQVPASGKL LVDPRYSTND QEESILQDII TRFPNVVLMK QTAQLRAMMT IIRDKETPKE
EFVFYADRLI RLLIEEALNE LPFEKKEVTT PLDVSYHGVS FYSKICGVSI VRAGESMESG
LRAVCRGCRI GKILIQRDET TAEPKLIYEK LPADIRDRWV MLLDPMCATA GSVCKAIEVL
LRLGVKEERI IFVNILAAPQ GIERVFKEYP KVRMVTAAVD ICLNSRYYIV PGIGDFGDRY
FGTM
