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 24-JAN-2024, entry version 188. 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; Pseudomonadota; 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 511145-b0142; -. DR EnsemblBacteria; AAC73253; AAC73253; b0142. 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 OrthoDB; 9808041at2; -. DR PhylomeDB; P26281; -. DR BioCyc; EcoCyc:H2PTERIDINEPYROPHOSPHOKIN-MONOMER; -. DR BioCyc; MetaCyc:H2PTERIDINEPYROPHOSPHOKIN-MONOMER; -. 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; 7,8-Dihydro-6-hydroxymethylpterin-pyrophosphokinase HPPK; 1. DR InterPro; IPR000550; Hppk. DR InterPro; IPR035907; Hppk_sf. DR NCBIfam; TIGR01498; folK; 1. DR PANTHER; PTHR43071; 2-AMINO-4-HYDROXY-6-HYDROXYMETHYLDIHYDROPTERIDINE PYROPHOSPHOKINASE; 1. DR PANTHER; PTHR43071:SF1; 2-AMINO-4-HYDROXY-6-HYDROXYMETHYLDIHYDROPTERIDINE PYROPHOSPHOKINASE; 1. DR Pfam; PF01288; HPPK; 1. DR SUPFAM; SSF55083; 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase, HPPK; 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 //