HGXR_TOXGO
ID HGXR_TOXGO Reviewed; 230 AA.
AC Q26997;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 106.
DE RecName: Full=Hypoxanthine-guanine-xanthine phosphoribosyltransferase;
DE Short=HGPRT;
DE Short=HGXPRT;
DE Short=HGXPRTase;
DE EC=2.4.2.22 {ECO:0000269|PubMed:10545171, ECO:0000269|PubMed:11188695};
DE EC=2.4.2.8 {ECO:0000269|PubMed:10545171, ECO:0000269|PubMed:11188695};
GN Name=HPRT;
OS Toxoplasma gondii.
OC Eukaryota; Sar; Alveolata; Apicomplexa; Conoidasida; Coccidia;
OC Eucoccidiorida; Eimeriorina; Sarcocystidae; Toxoplasma.
OX NCBI_TaxID=5811;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=RH;
RX PubMed=8088544; DOI=10.1016/0378-1119(94)90058-2;
RA Vasanthakumar G., van Ginkel S., Parish G.;
RT "Isolation and sequencing of a cDNA encoding the hypoxanthine-guanine
RT phosphoribosyltransferase from Toxoplasma gondii.";
RL Gene 147:153-154(1994).
RN [2]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS).
RX PubMed=8836106; DOI=10.1038/nsb1096-881;
RA Schumacher M.A., Carter D., Roos D.S., Ullman B., Brennan R.G.;
RT "Crystal structures of Toxoplasma gondii HGXPRTase reveal the catalytic
RT role of a long flexible loop.";
RL Nat. Struct. Biol. 3:881-887(1996).
RN [3]
RP X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS).
RX PubMed=10545170; DOI=10.1021/bi990507q;
RA Heroux A., White E.L., Ross L.J., Borhani D.W.;
RT "Crystal structures of the Toxoplasma gondii hypoxanthine-guanine
RT phosphoribosyltransferase-GMP and -IMP complexes: comparison of purine
RT binding interactions with the XMP complex.";
RL Biochemistry 38:14485-14494(1999).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF MUTANT ALA-150 IN COMPLEX WITH
RP XMP; PYROPHOSPHATE AND MAGNESIUM IONS, COFACTOR, CATALYTIC ACTIVITY,
RP SUBUNIT, ACTIVE SITE, AND MUTAGENESIS OF ASP-150.
RX PubMed=10545171; DOI=10.1021/bi990508i;
RA Heroux A., White E.L., Ross L.J., Davis R.L., Borhani D.W.;
RT "Crystal structure of Toxoplasma gondii hypoxanthine-guanine
RT phosphoribosyltransferase with bound XMP, pyrophosphate and two Mg2+ ions:
RT insights into the catalytic mechanism.";
RL Biochemistry 38:14495-14506(1999).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (1.05 ANGSTROMS) IN COMPLEX WITH MAGNESIUM;
RP PHOSPHORIBOSYLPYROPHOSPHATE AND 9-DEAZAGUANINE, CATALYTIC ACTIVITY, ACTIVE
RP SITE, AND FUNCTION.
RX PubMed=11188695; DOI=10.1016/s0969-2126(00)00546-3;
RA Heroux A., White E.L., Ross L.J., Kuzin A.P., Borhani D.W.;
RT "Substrate deformation in a hypoxanthine-guanine phosphoribosyltransferase
RT ternary complex: the structural basis for catalysis.";
RL Structure 8:1309-1318(2000).
CC -!- FUNCTION: Catalyzes the transfer of a ribosyl phosphate group from 5-
CC phosphoribose 1-diphosphate to the N(9) of hypoxanthine, guanine or
CC xanthine, leading to IMP, GMP and XMP, respectively. Plays a central
CC role in the generation of purine nucleotides through the purine salvage
CC pathway. {ECO:0000269|PubMed:11188695}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=diphosphate + IMP = 5-phospho-alpha-D-ribose 1-diphosphate +
CC hypoxanthine; Xref=Rhea:RHEA:17973, ChEBI:CHEBI:17368,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:58017, ChEBI:CHEBI:58053; EC=2.4.2.8;
CC Evidence={ECO:0000269|PubMed:10545171, ECO:0000269|PubMed:11188695};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:17975;
CC Evidence={ECO:0000269|PubMed:10545171, ECO:0000269|PubMed:11188695};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=diphosphate + GMP = 5-phospho-alpha-D-ribose 1-diphosphate +
CC guanine; Xref=Rhea:RHEA:25424, ChEBI:CHEBI:16235, ChEBI:CHEBI:33019,
CC ChEBI:CHEBI:58017, ChEBI:CHEBI:58115; EC=2.4.2.8;
CC Evidence={ECO:0000269|PubMed:10545171, ECO:0000269|PubMed:11188695};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:25426;
CC Evidence={ECO:0000269|PubMed:10545171, ECO:0000269|PubMed:11188695};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=diphosphate + XMP = 5-phospho-alpha-D-ribose 1-diphosphate +
CC xanthine; Xref=Rhea:RHEA:10800, ChEBI:CHEBI:17712, ChEBI:CHEBI:33019,
CC ChEBI:CHEBI:57464, ChEBI:CHEBI:58017; EC=2.4.2.22;
CC Evidence={ECO:0000269|PubMed:10545171, ECO:0000269|PubMed:11188695};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:10802;
CC Evidence={ECO:0000269|PubMed:10545171, ECO:0000269|PubMed:11188695};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:10545171};
CC Note=Binds 2 magnesium ions per subunit. The magnesium ions are
CC essentially bound to the substrate and have few direct interactions
CC with the protein. {ECO:0000269|PubMed:10545171};
CC -!- PATHWAY: Purine metabolism; GMP biosynthesis via salvage pathway; GMP
CC from guanine: step 1/1.
CC -!- PATHWAY: Purine metabolism; IMP biosynthesis via salvage pathway; IMP
CC from hypoxanthine: step 1/1.
CC -!- PATHWAY: Purine metabolism; XMP biosynthesis via salvage pathway; XMP
CC from xanthine: step 1/1.
CC -!- SUBUNIT: Homodimer at low ionic strength and homotetramer at high ionic
CC strength. {ECO:0000269|PubMed:10545171, ECO:0000269|PubMed:11188695}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- SIMILARITY: Belongs to the purine/pyrimidine phosphoribosyltransferase
CC family. {ECO:0000305}.
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DR EMBL; U09219; AAA57068.1; -; mRNA.
DR PDB; 1DBR; X-ray; 2.40 A; A/B/C/D=1-230.
DR PDB; 1FSG; X-ray; 1.05 A; A/C=1-230.
DR PDB; 1QK3; X-ray; 1.65 A; A/B/C/D=1-230.
DR PDB; 1QK4; X-ray; 1.90 A; A/B/C/D=1-230.
DR PDB; 1QK5; X-ray; 1.60 A; A/B=1-230.
DR PDBsum; 1DBR; -.
DR PDBsum; 1FSG; -.
DR PDBsum; 1QK3; -.
DR PDBsum; 1QK4; -.
DR PDBsum; 1QK5; -.
DR AlphaFoldDB; Q26997; -.
DR SMR; Q26997; -.
DR VEuPathDB; ToxoDB:TGARI_200320; -.
DR VEuPathDB; ToxoDB:TGCAST_200320; -.
DR VEuPathDB; ToxoDB:TGCOUG_200320; -.
DR VEuPathDB; ToxoDB:TGDOM2_200320; -.
DR VEuPathDB; ToxoDB:TGFOU_200320; -.
DR VEuPathDB; ToxoDB:TGGT1_200320; -.
DR VEuPathDB; ToxoDB:TGMAS_200320; -.
DR VEuPathDB; ToxoDB:TGME49_200320; -.
DR VEuPathDB; ToxoDB:TGP89_200320; -.
DR VEuPathDB; ToxoDB:TGPRC2_200320; -.
DR VEuPathDB; ToxoDB:TGRH88_083160; -.
DR VEuPathDB; ToxoDB:TGRUB_200320; -.
DR VEuPathDB; ToxoDB:TGVAND_200320; -.
DR VEuPathDB; ToxoDB:TGVEG_200320; -.
DR BRENDA; 2.4.2.8; 6411.
DR UniPathway; UPA00591; UER00648.
DR UniPathway; UPA00602; UER00658.
DR UniPathway; UPA00909; UER00887.
DR EvolutionaryTrace; Q26997; -.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0052657; F:guanine phosphoribosyltransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0004422; F:hypoxanthine phosphoribosyltransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0000166; F:nucleotide binding; IEA:UniProtKB-KW.
DR GO; GO:0000310; F:xanthine phosphoribosyltransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0032263; P:GMP salvage; IEA:UniProtKB-UniPathway.
DR GO; GO:0032264; P:IMP salvage; IEA:UniProtKB-UniPathway.
DR GO; GO:0006166; P:purine ribonucleoside salvage; IEA:UniProtKB-KW.
DR GO; GO:0032265; P:XMP salvage; IEA:UniProtKB-UniPathway.
DR CDD; cd06223; PRTases_typeI; 1.
DR DisProt; DP02927; -.
DR Gene3D; 3.40.50.2020; -; 1.
DR InterPro; IPR005904; Hxn_phspho_trans.
DR InterPro; IPR000836; PRibTrfase_dom.
DR InterPro; IPR029057; PRTase-like.
DR Pfam; PF00156; Pribosyltran; 1.
DR SUPFAM; SSF53271; SSF53271; 1.
DR TIGRFAMs; TIGR01203; HGPRTase; 1.
DR PROSITE; PS00103; PUR_PYR_PR_TRANSFER; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; Glycosyltransferase; Magnesium; Metal-binding;
KW Nucleotide-binding; Purine salvage; Transferase.
FT CHAIN 1..230
FT /note="Hypoxanthine-guanine-xanthine
FT phosphoribosyltransferase"
FT /id="PRO_0000139599"
FT ACT_SITE 150
FT /note="Proton acceptor"
FT /evidence="ECO:0000269|PubMed:10545171,
FT ECO:0000269|PubMed:11188695"
FT BINDING 79
FT /ligand="GMP"
FT /ligand_id="ChEBI:CHEBI:58115"
FT BINDING 146..154
FT /ligand="GMP"
FT /ligand_id="ChEBI:CHEBI:58115"
FT BINDING 178
FT /ligand="GMP"
FT /ligand_id="ChEBI:CHEBI:58115"
FT BINDING 199..200
FT /ligand="GMP"
FT /ligand_id="ChEBI:CHEBI:58115"
FT BINDING 206
FT /ligand="GMP"
FT /ligand_id="ChEBI:CHEBI:58115"
FT BINDING 206
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000269|PubMed:11188695"
FT MUTAGEN 150
FT /note="D->A: Strongly reduced catalytic activity."
FT /evidence="ECO:0000269|PubMed:10545171"
FT HELIX 6..8
FT /evidence="ECO:0007829|PDB:1FSG"
FT STRAND 9..11
FT /evidence="ECO:0007829|PDB:1DBR"
FT HELIX 29..31
FT /evidence="ECO:0007829|PDB:1FSG"
FT TURN 36..41
FT /evidence="ECO:0007829|PDB:1FSG"
FT STRAND 44..47
FT /evidence="ECO:0007829|PDB:1FSG"
FT HELIX 49..67
FT /evidence="ECO:0007829|PDB:1FSG"
FT STRAND 72..78
FT /evidence="ECO:0007829|PDB:1FSG"
FT TURN 79..81
FT /evidence="ECO:0007829|PDB:1FSG"
FT HELIX 82..98
FT /evidence="ECO:0007829|PDB:1FSG"
FT STRAND 109..119
FT /evidence="ECO:0007829|PDB:1FSG"
FT STRAND 122..130
FT /evidence="ECO:0007829|PDB:1FSG"
FT HELIX 134..137
FT /evidence="ECO:0007829|PDB:1FSG"
FT STRAND 141..152
FT /evidence="ECO:0007829|PDB:1FSG"
FT HELIX 153..163
FT /evidence="ECO:0007829|PDB:1FSG"
FT STRAND 168..178
FT /evidence="ECO:0007829|PDB:1FSG"
FT STRAND 189..195
FT /evidence="ECO:0007829|PDB:1FSG"
FT STRAND 200..202
FT /evidence="ECO:0007829|PDB:1FSG"
FT TURN 208..213
FT /evidence="ECO:0007829|PDB:1QK3"
FT STRAND 215..219
FT /evidence="ECO:0007829|PDB:1FSG"
FT HELIX 222..228
FT /evidence="ECO:0007829|PDB:1FSG"
SQ SEQUENCE 230 AA; 26386 MW; C3784254EF96361D CRC64;
MASKPIEDYG KGKGRIEPMY IPDNTFYNAD DFLVPPHCKP YIDKILLPGG LVKDRVEKLA
YDIHRTYFGE ELHIICILKG SRGFFNLLID YLATIQKYSG RESSVPPFFE HYVRLKSYQN
DNSTGQLTVL SDDLSIFRDK HVLIVEDIVD TGFTLTEFGE RLKAVGPKSM RIATLVEKRT
DRSNSLKGDF VGFSIEDVWI VGCCYDFNEM FRDFDHVAVL SDAARKKFEK
