Summary: 7,8-dihydro-6-hydroxymethylpterin-pyrophosphokinase (HPPK)
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2-amino-4-hydroxy-6-hydroxymethyldihydropteridine diphosphokinase Edit Wikipedia article
|PDB structures||RCSB PDB PDBe PDBsum|
|Gene Ontology||AmiGO / QuickGO|
7,8-dihydro-6-hydroxymethylpterin-pyrophosphokinase from haemophilus influenzae
|SCOPe||1hka / SUPFAM|
- ATP + 2-amino-4-hydroxy-6-hydroxymethyl-7,8-dihydropteridine 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. In the lower eukaryote Pneumocystis carinii, HPPK is the central domain of a multifunctional folate synthesis enzyme (gene fas).
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.
- 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): 5971â€“7. PMC 207135. PMID 1325970.
- 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): 213â€“8. doi:10.1016/0378-1119(92)90378-3. PMID 1313386.
- 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): 1582â€“92. PMID 4304228.
- Richey DP, Brown GM (1971). "Hydroxymethyldihydropteridine pyrophosphokinase and dihydropteroate synthetase from Escherichia coli". Methods Enzymol. 18B: 765â€“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): 5022â€“8. doi:10.1021/bi00840a052. PMID 4312465.
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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 ].
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
|Molecular function||2-amino-4-hydroxy-6-hydroxymethyldihydropteridine diphosphokinase activity (GO:0003848)|
|Biological process||folic acid-containing compound biosynthetic process (GO:0009396)|
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|Author:||Finn RD , Bateman A|
|Number in seed:||854|
|Number in full:||9204|
|Average length of the domain:||129.40 aa|
|Average identity of full alignment:||37 %|
|Average coverage of the sequence by the domain:||53.26 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||23|
|Download:||download the raw HMM for this family|
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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 122 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 sequence.
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AlphaFold Structure Predictions
The list of proteins below match this family and have AlphaFold predicted structures. Click on the protein accession to view the predicted structure.