HPRT_ECOLI
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 03-AUG-2022, entry version 130.
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; Proteobacteria; 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 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 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 SWISS-2DPAGE; P0A9M2; -.
DR jPOST; P0A9M2; -.
DR PaxDb; P0A9M2; -.
DR PRIDE; P0A9M2; -.
DR EnsemblBacteria; AAC73236; AAC73236; b0125.
DR EnsemblBacteria; BAB96700; BAB96700; BAB96700.
DR GeneID; 67416197; -.
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; TMDWMAV; -.
DR PhylomeDB; P0A9M2; -.
DR BioCyc; EcoCyc:HYPOXANPRIBOSYLTRAN-MON; -.
DR BioCyc; MetaCyc:HYPOXANPRIBOSYLTRAN-MON; -.
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: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: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 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; Reference proteome; Transferase.
FT CHAIN 1..178
FT /note="Hypoxanthine phosphoribosyltransferase"
FT /id="PRO_0000139632"
FT REGION 43..44
FT /note="Diphosphate"
FT /evidence="ECO:0000250|UniProtKB:P9WHQ9"
FT ACT_SITE 103
FT /note="Proton acceptor"
FT /evidence="ECO:0000305|PubMed:12070315"
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
