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60  structures 4045  species 2  interactions 4673  sequences 34  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
Identifiers
EC number 2.7.6.3
CAS number 37278-23-2
Databases
IntEnz IntEnz view
BRENDA BRENDA entry
ExPASy NiceZyme view
KEGG KEGG entry
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
Identifiers
Symbol HPPK
Pfam PF01288
InterPro IPR000550
PROSITE PDOC00631
SCOP 1hka
SUPERFAMILY 1hka

In enzymology, a 2-amino-4-hydroxy-6-hydroxymethyldihydropteridine diphosphokinase (EC 2.7.6.3) 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.

References

  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

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

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

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Alignments

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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We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

  Seed
(115)
Full
(4673)
Representative proteomes NCBI
(3316)
Meta
(2284)
RP15
(368)
RP35
(712)
RP55
(952)
RP75
(1118)
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1Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: ✓ available, x not generated, not available.

Format an alignment

  Seed
(115)
Full
(4673)
Representative proteomes NCBI
(3316)
Meta
(2284)
RP15
(368)
RP35
(712)
RP55
(952)
RP75
(1118)
Alignment:
Format:
Order:
Sequence:
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  Seed
(115)
Full
(4673)
Representative proteomes NCBI
(3316)
Meta
(2284)
RP15
(368)
RP35
(712)
RP55
(952)
RP75
(1118)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   Download   Download   Download   Download   Download   Download   Download  

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

External links

MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.

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Trees

This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

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Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

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Seed source: Prosite
Previous IDs: none
Type: Domain
Author: Finn RD, Bateman A
Number in seed: 115
Number in full: 4673
Average length of the domain: 125.90 aa
Average identity of full alignment: 37 %
Average coverage of the sequence by the domain: 60.63 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 21.5 21.5
Trusted cut-off 22.7 22.3
Noise cut-off 21.0 21.0
Model length: 127
Family (HMM) version: 15
Download: download the raw HMM for this family

Species distribution

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Interactions

There are 2 interactions for this family. More...

Pterin_bind HPPK

Structures

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 60 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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