ID   HPRT_ECOLI              Reviewed;         178 AA.
AC   P0A9M2; P36766;
DT   19-JUL-2005, integrated into UniProtKB/Swiss-Prot.
DT   19-JUL-2005, sequence version 1.
DT   27-MAR-2024, entry version 139.
DE   RecName: Full=Hypoxanthine phosphoribosyltransferase {ECO:0000303|PubMed:12070315};
DE            Short=HPRT {ECO:0000303|PubMed:12070315};
DE            EC=2.4.2.8 {ECO:0000269|PubMed:12070315};
DE   AltName: Full=6-oxopurine phosphoribosyltransferase {ECO:0000303|PubMed:12070315};
DE            Short=6-oxopurine PRTase {ECO:0000303|PubMed:12070315};
GN   Name=hpt; OrderedLocusNames=b0125, JW5009;
OS   Escherichia coli (strain K12).
OC   Bacteria; Pseudomonadota; Gammaproteobacteria; Enterobacterales;
OC   Enterobacteriaceae; Escherichia.
OX   NCBI_TaxID=83333;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
RX   PubMed=8202364; DOI=10.1093/nar/22.9.1637;
RA   Fujita N., Mori H., Yura T., Ishihama A.;
RT   "Systematic sequencing of the Escherichia coli genome: analysis of the 2.4-
RT   4.1 min (110,917-193,643 bp) region.";
RL   Nucleic Acids Res. 22:1637-1639(1994).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=K12 / MG1655 / ATCC 47076;
RX   PubMed=9278503; DOI=10.1126/science.277.5331.1453;
RA   Blattner F.R., Plunkett G. III, Bloch C.A., Perna N.T., Burland V.,
RA   Riley M., Collado-Vides J., Glasner J.D., Rode C.K., Mayhew G.F.,
RA   Gregor J., Davis N.W., Kirkpatrick H.A., Goeden M.A., Rose D.J., Mau B.,
RA   Shao Y.;
RT   "The complete genome sequence of Escherichia coli K-12.";
RL   Science 277:1453-1462(1997).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
RX   PubMed=16738553; DOI=10.1038/msb4100049;
RA   Hayashi K., Morooka N., Yamamoto Y., Fujita K., Isono K., Choi S.,
RA   Ohtsubo E., Baba T., Wanner B.L., Mori H., Horiuchi T.;
RT   "Highly accurate genome sequences of Escherichia coli K-12 strains MG1655
RT   and W3110.";
RL   Mol. Syst. Biol. 2:E1-E5(2006).
RN   [4]
RP   FUNCTION, CATALYTIC ACTIVITY, AND ACTIVITY REGULATION.
RX   PubMed=23927482; DOI=10.1021/jm400779n;
RA   Keough D.T., Hockova D., Rejman D., Spacek P., Vrbkova S., Krecmerova M.,
RA   Eng W.S., Jans H., West N.P., Naesens L.M., de Jersey J., Guddat L.W.;
RT   "Inhibition of the Escherichia coli 6-oxopurine phosphoribosyltransferases
RT   by nucleoside phosphonates: potential for new antibacterial agents.";
RL   J. Med. Chem. 56:6967-6984(2013).
RN   [5] {ECO:0007744|PDB:1G9S, ECO:0007744|PDB:1G9T, ECO:0007744|PDB:1GRV}
RP   X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) IN COMPLEXES WITH IMP; GMP AND
RP   MAGNESIUM, FUNCTION, CATALYTIC ACTIVITY, SUBSTRATE SPECIFICITY,
RP   BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, COFACTOR, ACTIVITY REGULATION,
RP   PATHWAY, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX   PubMed=12070315; DOI=10.1110/ps.0201002;
RA   Guddat L.W., Vos S., Martin J.L., Keough D.T., de Jersey J.;
RT   "Crystal structures of free, IMP-, and GMP-bound Escherichia coli
RT   hypoxanthine phosphoribosyltransferase.";
RL   Protein Sci. 11:1626-1638(2002).
RN   [6] {ECO:0007744|PDB:5KNR, ECO:0007744|PDB:5KNS, ECO:0007744|PDB:5KNT, ECO:0007744|PDB:5KNU, ECO:0007744|PDB:5KNV, ECO:0007744|PDB:5KNX}
RP   X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) IN COMPLEXES WITH NUCLEOSIDE
RP   PHOSPHONATES INHIBITORS, AND ACTIVITY REGULATION.
RX   DOI=10.1002/slct.201601679;
RA   Eng W.S., Hockova D., Spacek P., Baszczynski O., Janeba Z., Naesens L.,
RA   Keough D.T., Guddat L.W.;
RT   "Crystal Structures of Acyclic Nucleoside Phosphonates in Complex with
RT   Escherichia coli Hypoxanthine Phosphoribosyltransferase.";
RL   ChemistrySelect 1:6267-6276(2016).
CC   -!- FUNCTION: Purine salvage pathway enzyme which catalyzes the transfer of
CC       the ribosyl-5-phosphate group from 5-phospho-alpha-D-ribose 1-
CC       diphosphate (PRPP) to the N9 position of hypoxanthine to yield IMP
CC       (inosine 5'-monophosphate). To a lesser extent, can also act on guanine
CC       leading to GMP, but shows a highly less efficient activity with
CC       xanthine. {ECO:0000269|PubMed:12070315}.
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:12070315};
CC       PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:17975;
CC         Evidence={ECO:0000305|PubMed:12070315};
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:12070315};
CC       PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:25426;
CC         Evidence={ECO:0000305|PubMed:12070315};
CC   -!- COFACTOR:
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC         Evidence={ECO:0000305|PubMed:12070315};
CC   -!- ACTIVITY REGULATION: Inhibited by the product IMP (PubMed:12070315).
CC       Highly inhibited by nucleoside phosphonates, which are product analogs
CC       (PubMed:23927482, Ref.6). {ECO:0000269|PubMed:12070315,
CC       ECO:0000269|PubMed:23927482, ECO:0000269|Ref.6}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=12.5 uM for hypoxanthine (at pH 8.5 and 25 degrees Celsius)
CC         {ECO:0000269|PubMed:12070315};
CC         KM=294 uM for guanine (at pH 8.5 and 25 degrees Celsius)
CC         {ECO:0000269|PubMed:12070315};
CC         KM=25 uM for xanthine (at pH 8.5 and 25 degrees Celsius)
CC         {ECO:0000269|PubMed:12070315};
CC         KM=192 uM for 5-phospho-alpha-D-ribose 1-diphosphate (at pH 8.5 and
CC         25 degrees Celsius) {ECO:0000269|PubMed:12070315};
CC         Note=kcat is 59.0 sec(-1) with hypoxanthine as substrate. kcat is
CC         10.2 sec(-1) with guanine as substrate. kcat is 0.008 sec(-1) with
CC         xanthine as substrate (at pH 8.5 and 25 degrees Celsius).
CC         {ECO:0000269|PubMed:12070315};
CC   -!- PATHWAY: Purine metabolism; IMP biosynthesis via salvage pathway; IMP
CC       from hypoxanthine: step 1/1. {ECO:0000305|PubMed:12070315}.
CC   -!- SUBUNIT: Homotetramer. {ECO:0000269|PubMed:12070315}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm.
CC   -!- MISCELLANEOUS: E.coli cells express two distinct 6-oxopurine PRTases,
CC       with very different specificities for hypoxanthine, guanine, and
CC       xanthine. Salvage enzymes allow a more energy efficient synthesis of
CC       purine nucleoside monophosphates compared with the de novo pathway. The
CC       kinetic analysis suggests that E.coli HPRT is mainly responsible for
CC       the synthesis of IMP and that XGPRT primarily salvages guanine and
CC       xanthine. {ECO:0000305|PubMed:12070315}.
CC   -!- SIMILARITY: Belongs to the purine/pyrimidine phosphoribosyltransferase
CC       family. {ECO:0000305}.
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DR   EMBL; U00096; AAC73236.2; -; Genomic_DNA.
DR   EMBL; AP009048; BAB96700.2; -; Genomic_DNA.
DR   RefSeq; NP_414667.4; NC_000913.3.
DR   RefSeq; WP_000683335.1; NZ_STEB01000010.1.
DR   PDB; 1G9S; X-ray; 2.80 A; A/B=1-178.
DR   PDB; 1G9T; X-ray; 2.80 A; A/B=1-178.
DR   PDB; 1GRV; X-ray; 2.90 A; A/B=1-178.
DR   PDB; 5KNR; X-ray; 2.86 A; A/B=1-178.
DR   PDB; 5KNS; X-ray; 2.79 A; A/B=1-178.
DR   PDB; 5KNT; X-ray; 2.55 A; A/B=1-178.
DR   PDB; 5KNU; X-ray; 2.81 A; A/B=1-178.
DR   PDB; 5KNV; X-ray; 2.86 A; A/B=1-178.
DR   PDB; 5KNX; X-ray; 2.40 A; A/B=1-178.
DR   PDB; 8CAG; X-ray; 2.40 A; A/B=1-176.
DR   PDBsum; 1G9S; -.
DR   PDBsum; 1G9T; -.
DR   PDBsum; 1GRV; -.
DR   PDBsum; 5KNR; -.
DR   PDBsum; 5KNS; -.
DR   PDBsum; 5KNT; -.
DR   PDBsum; 5KNU; -.
DR   PDBsum; 5KNV; -.
DR   PDBsum; 5KNX; -.
DR   PDBsum; 8CAG; -.
DR   AlphaFoldDB; P0A9M2; -.
DR   SMR; P0A9M2; -.
DR   BioGRID; 4261679; 26.
DR   BioGRID; 850970; 3.
DR   DIP; DIP-47994N; -.
DR   IntAct; P0A9M2; 5.
DR   STRING; 511145.b0125; -.
DR   DrugBank; DB04566; Inosinic Acid.
DR   jPOST; P0A9M2; -.
DR   PaxDb; 511145-b0125; -.
DR   EnsemblBacteria; AAC73236; AAC73236; b0125.
DR   GeneID; 83577940; -.
DR   GeneID; 946624; -.
DR   KEGG; ecj:JW5009; -.
DR   KEGG; eco:b0125; -.
DR   PATRIC; fig|1411691.4.peg.2157; -.
DR   EchoBASE; EB4143; -.
DR   eggNOG; COG0634; Bacteria.
DR   HOGENOM; CLU_073615_0_0_6; -.
DR   InParanoid; P0A9M2; -.
DR   OMA; MQWRVAP; -.
DR   OrthoDB; 9802824at2; -.
DR   PhylomeDB; P0A9M2; -.
DR   BioCyc; EcoCyc:HYPOXANPRIBOSYLTRAN-MONOMER; -.
DR   BioCyc; MetaCyc:HYPOXANPRIBOSYLTRAN-MONOMER; -.
DR   BRENDA; 2.4.2.8; 2026.
DR   UniPathway; UPA00591; UER00648.
DR   EvolutionaryTrace; P0A9M2; -.
DR   PRO; PR:P0A9M2; -.
DR   Proteomes; UP000000318; Chromosome.
DR   Proteomes; UP000000625; Chromosome.
DR   GO; GO:0005829; C:cytosol; IDA:EcoCyc.
DR   GO; GO:0032991; C:protein-containing complex; IDA:EcoCyc.
DR   GO; GO:0052657; F:guanine phosphoribosyltransferase activity; IDA:EcoCyc.
DR   GO; GO:0097216; F:guanosine tetraphosphate binding; IDA:EcoCyc.
DR   GO; GO:0004422; F:hypoxanthine phosphoribosyltransferase activity; IDA:EcoCyc.
DR   GO; GO:0042802; F:identical protein binding; IPI:EcoCyc.
DR   GO; GO:0000287; F:magnesium ion binding; IDA:EcoCyc.
DR   GO; GO:0032263; P:GMP salvage; IDA:EcoliWiki.
DR   GO; GO:0006178; P:guanine salvage; IBA:GO_Central.
DR   GO; GO:0046100; P:hypoxanthine metabolic process; IBA:GO_Central.
DR   GO; GO:0032264; P:IMP salvage; IDA:EcoliWiki.
DR   GO; GO:0051289; P:protein homotetramerization; IDA:EcoCyc.
DR   GO; GO:0006166; P:purine ribonucleoside salvage; IEA:UniProtKB-KW.
DR   CDD; cd06223; PRTases_typeI; 1.
DR   Gene3D; 3.40.50.2020; -; 1.
DR   InterPro; IPR005904; Hxn_phspho_trans.
DR   InterPro; IPR000836; PRibTrfase_dom.
DR   InterPro; IPR029057; PRTase-like.
DR   NCBIfam; TIGR01203; HGPRTase; 1.
DR   PANTHER; PTHR43340:SF1; HYPOXANTHINE PHOSPHORIBOSYLTRANSFERASE; 1.
DR   PANTHER; PTHR43340; HYPOXANTHINE-GUANINE PHOSPHORIBOSYLTRANSFERASE; 1.
DR   Pfam; PF00156; Pribosyltran; 1.
DR   SUPFAM; SSF53271; PRTase-like; 1.
DR   PROSITE; PS00103; PUR_PYR_PR_TRANSFER; 1.
DR   SWISS-2DPAGE; P0A9M2; -.
PE   1: Evidence at protein level;
KW   3D-structure; Cytoplasm; Glycosyltransferase; Magnesium; Metal-binding;
KW   Nucleotide-binding; Purine salvage; Reference proteome; Transferase.
FT   CHAIN           1..178
FT                   /note="Hypoxanthine phosphoribosyltransferase"
FT                   /id="PRO_0000139632"
FT   ACT_SITE        103
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000305|PubMed:12070315"
FT   BINDING         43
FT                   /ligand="diphosphate"
FT                   /ligand_id="ChEBI:CHEBI:33019"
FT                   /evidence="ECO:0000250|UniProtKB:P9WHQ9"
FT   BINDING         44
FT                   /ligand="diphosphate"
FT                   /ligand_id="ChEBI:CHEBI:33019"
FT                   /evidence="ECO:0000250|UniProtKB:P9WHQ9"
FT   BINDING         99
FT                   /ligand="GMP"
FT                   /ligand_id="ChEBI:CHEBI:58115"
FT                   /evidence="ECO:0000269|PubMed:12070315,
FT                   ECO:0007744|PDB:1G9T"
FT   BINDING         99
FT                   /ligand="IMP"
FT                   /ligand_id="ChEBI:CHEBI:58053"
FT                   /evidence="ECO:0000269|PubMed:12070315,
FT                   ECO:0007744|PDB:1G9S"
FT   BINDING         99
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000269|PubMed:12070315,
FT                   ECO:0007744|PDB:1GRV"
FT   BINDING         100
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000269|PubMed:12070315,
FT                   ECO:0007744|PDB:1GRV"
FT   BINDING         103..108
FT                   /ligand="GMP"
FT                   /ligand_id="ChEBI:CHEBI:58115"
FT                   /evidence="ECO:0000269|PubMed:12070315,
FT                   ECO:0007744|PDB:1G9T"
FT   BINDING         103..108
FT                   /ligand="IMP"
FT                   /ligand_id="ChEBI:CHEBI:58053"
FT                   /evidence="ECO:0000269|PubMed:12070315,
FT                   ECO:0007744|PDB:1G9S"
FT   BINDING         131
FT                   /ligand="GMP"
FT                   /ligand_id="ChEBI:CHEBI:58115"
FT                   /evidence="ECO:0000269|PubMed:12070315,
FT                   ECO:0007744|PDB:1G9T"
FT   BINDING         131
FT                   /ligand="IMP"
FT                   /ligand_id="ChEBI:CHEBI:58053"
FT                   /evidence="ECO:0000269|PubMed:12070315,
FT                   ECO:0007744|PDB:1G9S"
FT   BINDING         159
FT                   /ligand="GMP"
FT                   /ligand_id="ChEBI:CHEBI:58115"
FT                   /evidence="ECO:0000269|PubMed:12070315,
FT                   ECO:0007744|PDB:1G9T"
FT   BINDING         165
FT                   /ligand="diphosphate"
FT                   /ligand_id="ChEBI:CHEBI:33019"
FT                   /evidence="ECO:0000250|UniProtKB:P9WHQ9"
FT   STRAND          3..9
FT                   /evidence="ECO:0007829|PDB:5KNX"
FT   HELIX           11..29
FT                   /evidence="ECO:0007829|PDB:5KNX"
FT   TURN            30..32
FT                   /evidence="ECO:0007829|PDB:1G9T"
FT   STRAND          36..41
FT                   /evidence="ECO:0007829|PDB:5KNX"
FT   TURN            42..45
FT                   /evidence="ECO:0007829|PDB:5KNX"
FT   HELIX           46..54
FT                   /evidence="ECO:0007829|PDB:5KNX"
FT   STRAND          61..67
FT                   /evidence="ECO:0007829|PDB:5KNX"
FT   TURN            73..76
FT                   /evidence="ECO:0007829|PDB:5KNX"
FT   STRAND          82..84
FT                   /evidence="ECO:0007829|PDB:5KNX"
FT   STRAND          93..104
FT                   /evidence="ECO:0007829|PDB:5KNX"
FT   HELIX           106..116
FT                   /evidence="ECO:0007829|PDB:5KNX"
FT   STRAND          121..130
FT                   /evidence="ECO:0007829|PDB:5KNX"
FT   HELIX           132..134
FT                   /evidence="ECO:0007829|PDB:5KNX"
FT   STRAND          142..147
FT                   /evidence="ECO:0007829|PDB:5KNX"
FT   STRAND          153..155
FT                   /evidence="ECO:0007829|PDB:5KNX"
FT   STRAND          160..162
FT                   /evidence="ECO:0007829|PDB:5KNS"
FT   STRAND          168..175
FT                   /evidence="ECO:0007829|PDB:5KNX"
SQ   SEQUENCE   178 AA;  20115 MW;  E1A75EB68231DC32 CRC64;
     MKHTVEVMIP EAEIKARIAE LGRQITERYK DSGSDMVLVG LLRGSFMFMA DLCREVQVSH
     EVDFMTASSY GSGMSTTRDV KILKDLDEDI RGKDVLIVED IIDSGNTLSK VREILSLREP
     KSLAICTLLD KPSRREVNVP VEFIGFSIPD EFVVGYGIDY AQRYRHLPYI GKVILLDE
//