HPPK_ECOLI
ID HPPK_ECOLI Reviewed; 159 AA.
AC P26281;
DT 01-MAY-1992, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 182.
DE RecName: Full=2-amino-4-hydroxy-6-hydroxymethyldihydropteridine pyrophosphokinase;
DE EC=2.7.6.3 {ECO:0000269|PubMed:1325970};
DE AltName: Full=6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase;
DE Short=PPPK;
DE AltName: Full=7,8-dihydro-6-hydroxymethylpterin-pyrophosphokinase;
DE Short=HPPK;
GN Name=folK; OrderedLocusNames=b0142, JW0138;
OS Escherichia coli (strain K12).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Escherichia.
OX NCBI_TaxID=83333;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROTEIN SEQUENCE OF 2-20, FUNCTION,
RP CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, AND PATHWAY.
RC STRAIN=K12 / MC4100 / ATCC 35695 / DSM 6574;
RX PubMed=1325970; DOI=10.1128/jb.174.18.5971-5977.1992;
RA Talarico T.L., Ray P.H., Dev I.K., Merrill B.M., Dallas W.S.;
RT "Cloning, sequence analysis, and overexpression of Escherichia coli folK,
RT the gene coding for 7,8-dihydro-6-hydroxymethylpterin-pyrophosphokinase.";
RL J. Bacteriol. 174:5971-5977(1992).
RN [2]
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 [3]
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 [4]
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 [5]
RP PROTEIN SEQUENCE OF 2-29.
RX PubMed=1657875; DOI=10.1128/jb.173.21.7029-7032.1991;
RA Talarico T.L., Dev I.K., Dallas W.S., Ferone R., Ray P.H.;
RT "Purification and partial characterization of 7,8-dihydro-6-
RT hydroxymethylpterin-pyrophosphokinase and 7,8-dihydropteroate synthase from
RT Escherichia coli MC4100.";
RL J. Bacteriol. 173:7029-7032(1991).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-28.
RC STRAIN=K12 / RP437;
RX PubMed=2537812; DOI=10.1128/jb.171.3.1254-1261.1989;
RA Liu J., Parkinson J.S.;
RT "Genetics and sequence analysis of the pcnB locus, an Escherichia coli gene
RT involved in plasmid copy number control.";
RL J. Bacteriol. 171:1254-1261(1989).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS).
RX PubMed=10378268; DOI=10.1016/s0969-2126(99)80065-3;
RA Xiao B., Shi G., Chen X., Yan H., Ji X.;
RT "Crystal structure of 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase,
RT a potential target for the development of novel antimicrobial agents.";
RL Structure 7:489-496(1999).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS).
RX PubMed=10452528; DOI=10.1016/s0014-5793(99)00860-1;
RA Stammers D.K., Achari A., Somers D.O., Bryant P.K., Rosemond J.,
RA Scott D.L., Champness J.N.;
RT "2.0 A X-ray structure of the ternary complex of 7,8-dihydro-6-
RT hydroxymethylpterinpyrophosphokinase from Escherichia coli with ATP and a
RT substrate analogue.";
RL FEBS Lett. 456:49-53(1999).
CC -!- FUNCTION: Catalyzes the transfer of pyrophosphate from adenosine
CC triphosphate (ATP) to 6-hydroxymethyl-7,8-dihydropterin, an enzymatic
CC step in folate biosynthesis pathway. {ECO:0000269|PubMed:1325970}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=6-hydroxymethyl-7,8-dihydropterin + ATP = (7,8-dihydropterin-
CC 6-yl)methyl diphosphate + AMP + H(+); Xref=Rhea:RHEA:11412,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:44841,
CC ChEBI:CHEBI:72950, ChEBI:CHEBI:456215; EC=2.7.6.3;
CC Evidence={ECO:0000269|PubMed:1325970};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:11413;
CC Evidence={ECO:0000269|PubMed:1325970};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Temperature dependence:
CC Thermostable. Retains 75% of its activity after heating 30 minutes at
CC 96 degrees Celsius. {ECO:0000269|PubMed:1325970};
CC -!- PATHWAY: Cofactor biosynthesis; tetrahydrofolate biosynthesis; 2-amino-
CC 4-hydroxy-6-hydroxymethyl-7,8-dihydropteridine diphosphate from 7,8-
CC dihydroneopterin triphosphate: step 4/4. {ECO:0000305|PubMed:1325970}.
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:1325970}.
CC -!- SIMILARITY: Belongs to the HPPK family. {ECO:0000305}.
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DR EMBL; L06495; AAB53446.1; -; Genomic_DNA.
DR EMBL; M20574; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; U00096; AAC73253.1; -; Genomic_DNA.
DR EMBL; AP009048; BAB96719.1; -; Genomic_DNA.
DR PIR; A43325; A43325.
DR RefSeq; NP_414684.1; NC_000913.3.
DR RefSeq; WP_000215139.1; NZ_STEB01000010.1.
DR PDB; 1DY3; X-ray; 2.00 A; A=2-159.
DR PDB; 1EQ0; NMR; -; A=2-159.
DR PDB; 1EQM; X-ray; 1.50 A; A=2-159.
DR PDB; 1EX8; X-ray; 1.85 A; A=2-159.
DR PDB; 1F9H; X-ray; 1.50 A; A=2-159.
DR PDB; 1G4C; X-ray; 1.65 A; A/B=2-159.
DR PDB; 1HKA; X-ray; 1.50 A; A=2-159.
DR PDB; 1HQ2; X-ray; 1.25 A; A=2-159.
DR PDB; 1IM6; X-ray; 1.74 A; A=2-159.
DR PDB; 1KBR; X-ray; 1.55 A; A=2-159.
DR PDB; 1Q0N; X-ray; 1.25 A; A=2-159.
DR PDB; 1RAO; X-ray; 1.56 A; A=2-159.
DR PDB; 1RB0; X-ray; 1.35 A; A=2-159.
DR PDB; 1RTZ; X-ray; 1.33 A; A=2-159.
DR PDB; 1RU1; X-ray; 1.40 A; A/B=2-159.
DR PDB; 1RU2; X-ray; 1.48 A; A=2-159.
DR PDB; 1TMJ; X-ray; 1.45 A; A=2-159.
DR PDB; 1TMM; X-ray; 1.25 A; A/B=2-159.
DR PDB; 2F63; NMR; -; A=2-159.
DR PDB; 2F65; NMR; -; A=2-159.
DR PDB; 3HCX; X-ray; 1.75 A; A=2-159.
DR PDB; 3HD1; X-ray; 1.30 A; A=2-159.
DR PDB; 3HD2; X-ray; 1.10 A; A=2-159.
DR PDB; 3HSD; X-ray; 1.65 A; A/B=2-159.
DR PDB; 3HSG; X-ray; 1.14 A; A=2-159.
DR PDB; 3HSJ; X-ray; 1.18 A; A=2-159.
DR PDB; 3HSZ; X-ray; 1.40 A; A=2-159.
DR PDB; 3HT0; X-ray; 1.40 A; A=2-159.
DR PDB; 3ILI; X-ray; 1.45 A; A=2-159.
DR PDB; 3ILJ; X-ray; 1.65 A; A=2-159.
DR PDB; 3ILL; X-ray; 1.73 A; A=2-159.
DR PDB; 3ILO; X-ray; 1.10 A; A=2-159.
DR PDB; 3IP0; X-ray; 0.89 A; A=2-159.
DR PDB; 3KUE; X-ray; 1.54 A; A=2-159.
DR PDB; 3KUG; X-ray; 2.00 A; A=2-159.
DR PDB; 3KUH; X-ray; 1.35 A; A=2-159.
DR PDB; 3UD5; X-ray; 2.00 A; A=2-159.
DR PDB; 3UDE; X-ray; 1.88 A; A=2-159.
DR PDB; 3UDV; X-ray; 1.88 A; A=2-159.
DR PDB; 4F7V; X-ray; 1.73 A; A=2-159.
DR PDB; 4M5G; X-ray; 1.31 A; A=1-159.
DR PDB; 4M5H; X-ray; 1.11 A; A=1-159.
DR PDB; 4M5I; X-ray; 1.08 A; A=1-159.
DR PDB; 4M5J; X-ray; 1.70 A; A=1-159.
DR PDB; 4M5K; X-ray; 1.30 A; A=1-159.
DR PDB; 4M5L; X-ray; 1.09 A; A=1-159.
DR PDB; 4M5M; X-ray; 1.12 A; A=1-159.
DR PDB; 4M5N; X-ray; 2.00 A; A/B=1-159.
DR PDB; 5ETK; X-ray; 1.09 A; A=1-159.
DR PDB; 5ETL; X-ray; 1.82 A; A/B/C/D=1-159.
DR PDB; 5ETM; X-ray; 1.46 A; A=1-159.
DR PDB; 5ETN; X-ray; 1.40 A; A=1-159.
DR PDB; 5ETO; X-ray; 1.07 A; A=1-159.
DR PDB; 5ETP; X-ray; 1.05 A; A=1-159.
DR PDB; 6AN4; X-ray; 1.47 A; A=2-159.
DR PDB; 6AN6; X-ray; 2.30 A; A/B=2-159.
DR PDB; 7KDO; X-ray; 1.60 A; A=2-159.
DR PDB; 7KDR; X-ray; 1.49 A; A=2-159.
DR PDBsum; 1DY3; -.
DR PDBsum; 1EQ0; -.
DR PDBsum; 1EQM; -.
DR PDBsum; 1EX8; -.
DR PDBsum; 1F9H; -.
DR PDBsum; 1G4C; -.
DR PDBsum; 1HKA; -.
DR PDBsum; 1HQ2; -.
DR PDBsum; 1IM6; -.
DR PDBsum; 1KBR; -.
DR PDBsum; 1Q0N; -.
DR PDBsum; 1RAO; -.
DR PDBsum; 1RB0; -.
DR PDBsum; 1RTZ; -.
DR PDBsum; 1RU1; -.
DR PDBsum; 1RU2; -.
DR PDBsum; 1TMJ; -.
DR PDBsum; 1TMM; -.
DR PDBsum; 2F63; -.
DR PDBsum; 2F65; -.
DR PDBsum; 3HCX; -.
DR PDBsum; 3HD1; -.
DR PDBsum; 3HD2; -.
DR PDBsum; 3HSD; -.
DR PDBsum; 3HSG; -.
DR PDBsum; 3HSJ; -.
DR PDBsum; 3HSZ; -.
DR PDBsum; 3HT0; -.
DR PDBsum; 3ILI; -.
DR PDBsum; 3ILJ; -.
DR PDBsum; 3ILL; -.
DR PDBsum; 3ILO; -.
DR PDBsum; 3IP0; -.
DR PDBsum; 3KUE; -.
DR PDBsum; 3KUG; -.
DR PDBsum; 3KUH; -.
DR PDBsum; 3UD5; -.
DR PDBsum; 3UDE; -.
DR PDBsum; 3UDV; -.
DR PDBsum; 4F7V; -.
DR PDBsum; 4M5G; -.
DR PDBsum; 4M5H; -.
DR PDBsum; 4M5I; -.
DR PDBsum; 4M5J; -.
DR PDBsum; 4M5K; -.
DR PDBsum; 4M5L; -.
DR PDBsum; 4M5M; -.
DR PDBsum; 4M5N; -.
DR PDBsum; 5ETK; -.
DR PDBsum; 5ETL; -.
DR PDBsum; 5ETM; -.
DR PDBsum; 5ETN; -.
DR PDBsum; 5ETO; -.
DR PDBsum; 5ETP; -.
DR PDBsum; 6AN4; -.
DR PDBsum; 6AN6; -.
DR PDBsum; 7KDO; -.
DR PDBsum; 7KDR; -.
DR AlphaFoldDB; P26281; -.
DR BMRB; P26281; -.
DR SMR; P26281; -.
DR IntAct; P26281; 2.
DR STRING; 511145.b0142; -.
DR BindingDB; P26281; -.
DR ChEMBL; CHEMBL3217379; -.
DR DrugBank; DB04158; 6-(adenosine tetraphosphate-methyl)-7,8-dihydropterin.
DR DrugBank; DB02119; 6-Hydroxymethyl-7,8-Dihydropterin.
DR DrugBank; DB03197; 6-Hydroxymethylpterin.
DR DrugBank; DB04047; 6-hydroxymethylpterin diphosphate.
DR DrugBank; DB04610; 7,8-dihydro-6-hydroxymethyl-7-methyl-7-[2-phenylethyl]-pterin.
DR DrugBank; DB02596; alpha,beta-Methyleneadenosine 5'-triphosphate.
DR jPOST; P26281; -.
DR PaxDb; P26281; -.
DR PRIDE; P26281; -.
DR EnsemblBacteria; AAC73253; AAC73253; b0142.
DR EnsemblBacteria; BAB96719; BAB96719; BAB96719.
DR GeneID; 948792; -.
DR KEGG; ecj:JW0138; -.
DR KEGG; eco:b0142; -.
DR PATRIC; fig|1411691.4.peg.2139; -.
DR EchoBASE; EB1348; -.
DR eggNOG; COG0801; Bacteria.
DR HOGENOM; CLU_097916_0_1_6; -.
DR InParanoid; P26281; -.
DR OMA; QVILRQN; -.
DR PhylomeDB; P26281; -.
DR BioCyc; EcoCyc:H2PTERIDINEPYROPHOSPHOKIN-MON; -.
DR BioCyc; MetaCyc:H2PTERIDINEPYROPHOSPHOKIN-MON; -.
DR BRENDA; 2.7.6.3; 2026.
DR SABIO-RK; P26281; -.
DR UniPathway; UPA00077; UER00155.
DR EvolutionaryTrace; P26281; -.
DR PRO; PR:P26281; -.
DR Proteomes; UP000000318; Chromosome.
DR Proteomes; UP000000625; Chromosome.
DR GO; GO:0003848; F:2-amino-4-hydroxy-6-hydroxymethyldihydropteridine diphosphokinase activity; IDA:EcoliWiki.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016301; F:kinase activity; IEA:UniProtKB-KW.
DR GO; GO:0000287; F:magnesium ion binding; IDA:EcoCyc.
DR GO; GO:0046656; P:folic acid biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR GO; GO:0046654; P:tetrahydrofolate biosynthetic process; IEA:UniProtKB-UniPathway.
DR CDD; cd00483; HPPK; 1.
DR Gene3D; 3.30.70.560; -; 1.
DR InterPro; IPR000550; Hppk.
DR InterPro; IPR035907; Hppk_sf.
DR Pfam; PF01288; HPPK; 1.
DR SUPFAM; SSF55083; SSF55083; 1.
DR TIGRFAMs; TIGR01498; folK; 1.
DR PROSITE; PS00794; HPPK; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ATP-binding; Direct protein sequencing; Folate biosynthesis;
KW Kinase; Nucleotide-binding; Reference proteome; Transferase.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:1325970,
FT ECO:0000269|PubMed:1657875"
FT CHAIN 2..159
FT /note="2-amino-4-hydroxy-6-hydroxymethyldihydropteridine
FT pyrophosphokinase"
FT /id="PRO_0000168249"
FT STRAND 3..10
FT /evidence="ECO:0007829|PDB:3IP0"
FT STRAND 12..14
FT /evidence="ECO:0007829|PDB:1RU1"
FT HELIX 15..27
FT /evidence="ECO:0007829|PDB:3IP0"
FT STRAND 32..37
FT /evidence="ECO:0007829|PDB:3IP0"
FT STRAND 41..43
FT /evidence="ECO:0007829|PDB:3IP0"
FT STRAND 46..48
FT /evidence="ECO:0007829|PDB:5ETO"
FT STRAND 49..51
FT /evidence="ECO:0007829|PDB:3IP0"
FT STRAND 54..63
FT /evidence="ECO:0007829|PDB:3IP0"
FT HELIX 67..80
FT /evidence="ECO:0007829|PDB:3IP0"
FT STRAND 81..83
FT /evidence="ECO:0007829|PDB:7KDR"
FT TURN 84..86
FT /evidence="ECO:0007829|PDB:1IM6"
FT STRAND 87..90
FT /evidence="ECO:0007829|PDB:3HD2"
FT HELIX 91..93
FT /evidence="ECO:0007829|PDB:1RU2"
FT STRAND 96..102
FT /evidence="ECO:0007829|PDB:3IP0"
FT STRAND 107..111
FT /evidence="ECO:0007829|PDB:5ETP"
FT STRAND 113..115
FT /evidence="ECO:0007829|PDB:3IP0"
FT HELIX 119..121
FT /evidence="ECO:0007829|PDB:3IP0"
FT HELIX 123..132
FT /evidence="ECO:0007829|PDB:3IP0"
FT STRAND 139..141
FT /evidence="ECO:0007829|PDB:2F63"
FT HELIX 144..151
FT /evidence="ECO:0007829|PDB:3IP0"
SQ SEQUENCE 159 AA; 18079 MW; 67301CD634D0A174 CRC64;
MTVAYIAIGS NLASPLEQVN AALKALGDIP ESHILTVSSF YRTPPLGPQD QPDYLNAAVA
LETSLAPEEL LNHTQRIELQ QGRVRKAERW GPRTLDLDIM LFGNEVINTE RLTVPHYDMK
NRGFMLWPLF EIAPELVFPD GEMLRQILHT RAFDKLNKW
