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73  structures 17811  species 3  interactions 20195  sequences 45  architectures

Family: HPPK (PF01288)

Summary: 7,8-dihydro-6-hydroxymethylpterin-pyrophosphokinase (HPPK)

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This is the Wikipedia entry entitled "2-amino-4-hydroxy-6-hydroxymethyldihydropteridine diphosphokinase". More...

2-amino-4-hydroxy-6-hydroxymethyldihydropteridine diphosphokinase Edit Wikipedia article

2-amino-4-hydroxy-6-hydroxymethyldihydropteridine diphosphokinase
EC number
CAS number 37278-23-2
IntEnz IntEnz view
ExPASy NiceZyme view
MetaCyc metabolic pathway
PRIAM profile
PDB structures RCSB PDB PDBe PDBsum
Gene Ontology AmiGO / EGO
7,8-dihydro-6-hydroxymethylpterin-pyrophosphokinase (HPPK)
PDB 1cbk EBI.jpg
7,8-dihydro-6-hydroxymethylpterin-pyrophosphokinase from haemophilus influenzae
Symbol HPPK
Pfam PF01288
InterPro IPR000550
SCOP 1hka
CDD cd00483

In enzymology, a 2-amino-4-hydroxy-6-hydroxymethyldihydropteridine diphosphokinase (EC is an enzyme that catalyzes the chemical reaction

ATP + 2-amino-4-hydroxy-6-hydroxymethyl-7,8-dihydropteridine \rightleftharpoons AMP + (2-amino-4-hydroxy-7,8-dihydropteridin-6-yl)methyl diphosphate

Thus, the two substrates of this enzyme are ATP and 2-amino-4-hydroxy-6-hydroxymethyl-7,8-dihydropteridine, whereas its two products are AMP and (2-amino-4-hydroxy-7,8-dihydropteridin-6-yl)methyl diphosphate.

This enzyme belongs to the family of transferases, specifically those transferring two phosphorus-containing groups (diphosphotransferases). The systematic name of this enzyme class is ATP:2-amino-4-hydroxy-6-hydroxymethyl-7,8-dihydropteridine 6'-diphosphotransferase. Other names in common use include 2-amino-4-hydroxy-6-hydroxymethyldihydropteridine pyrophosphokinase, H2-pteridine-CH2OH pyrophosphokinase, 7,8-dihydroxymethylpterin-pyrophosphokinase, HPPK, 7,8-dihydro-6-hydroxymethylpterin pyrophosphokinase, and hydroxymethyldihydropteridine pyrophosphokinase. This enzyme participates in folate biosynthesis.

This enzyme catalyses the first step in a three-step pathway leading to 7,8 dihydrofolate. Bacterial HPPK (gene folK or sulD) is a protein of 160 to 270 amino acids.[1] In the lower eukaryote Pneumocystis carinii, HPPK is the central domain of a multifunctional folate synthesis enzyme (gene fas).[2]

Structural studies

As of late 2007, 23 structures have been solved for this class of enzymes, with PDB accession codes 1DY3, 1EQ0, 1EQM, 1EX8, 1F9H, 1F9Y, 1G4C, 1HKA, 1HQ2, 1IM6, 1KBR, 1Q0N, 1RAO, 1RB0, 1RTZ, 1RU1, 1RU2, 1TMJ, 1TMM, 2BMB, 2CG8, 2F63, and 2F65.


  1. ^ Talarico TL, Ray PH, Dev IK, Merrill BM, Dallas WS (September 1992). "Cloning, sequence analysis, and overexpression of Escherichia coli folK, the gene coding for 7,8-dihydro-6-hydroxymethylpterin-pyrophosphokinase". J. Bacteriol. 174 (18): 5971–7. PMC 207135. PMID 1325970. 
  2. ^ Volpe F, Dyer M, Scaife JG, Darby G, Stammers DK, Delves CJ (March 1992). "The multifunctional folic acid synthesis fas gene of Pneumocystis carinii appears to encode dihydropteroate synthase and hydroxymethyldihydropterin pyrophosphokinase". Gene 112 (2): 213–8. doi:10.1016/0378-1119(92)90378-3. PMID 1313386. 

Further reading

  • Richey DP, Brown GM (1969). "The biosynthesis of folic acid. IX. Purification and properties of the enzymes required for the formation of dihydropteroic acid". J. Biol. Chem. 244 (6): 1582–92. PMID 4304228. 
  • Richey DP and Brown GM (1971). "Hydroxymethyldihydropteridine pyrophosphokinase and dihydropteroate synthetase from Escherichia coli". Methods Enzymol. 18B: 765–771. doi:10.1016/s0076-6879(71)18150-5. 
  • Shiota T, Baugh CM, Jackson R, Dillard R (1969). "The enzymatic synthesis of hydroxymethyldihydropteridine pyrophosphate and dihydrofolate". Biochemistry. 8 (12): 5022–8. doi:10.1021/bi00840a052. PMID 4312465. 

This article incorporates text from the public domain Pfam and InterPro IPR000550

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7,8-dihydro-6-hydroxymethylpterin-pyrophosphokinase (HPPK) Provide feedback

No Pfam abstract.

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR000550

All organisms require reduced folate cofactors for the synthesis of a variety of metabolites. Most microorganisms must synthesise folate de novo because they lack the active transport system of higher vertebrate cells which allows these organisms to use dietary folates. Enzymes involved in folate biosynthesis are therefore targets for a variety of antimicrobial agents such as trimethoprim or sulphonamides. 7,8-dihydro-6-hydroxymethylpterin-pyrophosphokinase (EC) (HPPK) catalyses the attachment of pyrophosphate to 6-hydroxymethyl-7,8-dihydropterin to form 6-hydroxymethyl-7,8-dihydropteridine pyrophosphate. This is the first step in a three-step pathway leading to 7,8 dihydrofolate. Bacterial HPPK (gene folK or sulD) [PUBMED:1325970] is a protein of 160 to 270 amino acids. In the lower eukaryote Pneumocystis carinii, HPPK is the central domain of a multifunctional folate synthesis enzyme (gene fas) [PUBMED:1313386].

Gene Ontology

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Domain organisation

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We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the NCBI sequence database, and our metagenomics sequence database. More...

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Seed source: Prosite
Previous IDs: none
Type: Domain
Author: Finn RD, Bateman A
Number in seed: 1134
Number in full: 20195
Average length of the domain: 126.60 aa
Average identity of full alignment: 41 %
Average coverage of the sequence by the domain: 69.15 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 80369284 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 21.5 21.5
Trusted cut-off 21.7 21.6
Noise cut-off 20.6 20.5
Model length: 114
Family (HMM) version: 16
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Species distribution

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Archea Archea Eukaryota Eukaryota
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Viroids Viroids Unclassified sequence Unclassified sequence


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There are 3 interactions for this family. More...

FolB Pterin_bind HPPK


For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the HPPK domain has been found. There are 73 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.

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