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

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

2-amino-4-hydroxy-6-hydroxymethyldihydropteridine diphosphokinase

Identifiers

Databases

PDB structures

AmiGO / EGO

Search
PMC	articles
PubMed	articles

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

7,8-dihydro-6-hydroxymethylpterin-pyrophosphokinase from haemophilus influenzae

Identifiers

Symbol

HPPK

Available protein structures:
Pfam	structures
PDB	RCSB PDB; PDBe
PDBsum	structure summary

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]

[edit] 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.

[edit] References

^ 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): 59717. PMC 207135. PMID 1325970. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=207135.
^ 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): 2138. doi:10.1016/0378-1119(92)90378-3. PMID 1313386.

[edit] 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): 158292. PMID 4304228.
Richey DP and Brown GM (1971). "Hydroxymethyldihydropteridine pyrophosphokinase and dihydropteroate synthetase from Escherichia coli". Methods Enzymol. 18B: 765771.
Shiota T, Baugh CM, Jackson R, Dillard R (1969). "The enzymatic synthesis of hydroxymethyldihydropteridine pyrophosphate and dihydrofolate". Biochemistry. 8 (12): 50228. 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

HOMSTRAD:	HPPK
PANDIT:	PF01288
PROSITE:	PDOC00631
Pseudofam:	PF01288
SCOP:	1hka
SYSTERS:	HPPK

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.

Molecular function	2-amino-4-hydroxy-6-hydroxymethyldihydropteridine diphosphokinase activity (GO:0003848)
Biological process	folic acid-containing compound biosynthetic process (GO:0009396)

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...

There are various ways to view or download the sequence alignments that we store. We provide several sequence viewers and a plain-text Stockholm-format file for download.

Alignment types

We make a range of alignments for each Pfam-A family:

seed: the curated alignment from which the HMM for the family is built
full: the alignment generated by searching the sequence database using the HMM
RP15/RP35/RP55/RP75: Representative Proteomes (RPs) at 15%, 35%, 55% and 75% co-membership thresholds
NCBI: alignment generated by searching the NCBI sequence database using the family HMM
meta: alignment generated by searching the metagenomics sequence database using the family HMM

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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)
	Seed (115)	Full (4673)	RP15 (368)	RP35 (712)	RP55 (952)	RP75 (1118)	NCBI (3316)	Meta (2284)
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HTML	View	View	View	View	View	View
PP/heatmap	₁	View	View	View	View	View
Pfam viewer	View	View

¹Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: available, not generated, — not available.

Format an alignment

	Seed (115)	Full (4673)	Representative proteomes				NCBI (3316)	Meta (2284)
	Seed (115)	Full (4673)	RP15 (368)	RP35 (712)	RP55 (952)	RP75 (1118)	NCBI (3316)	Meta (2284)
Alignment:
Format:
Order:	Tree Alphabetical
Sequence:	Inserts lower case All upper case
Gaps:
Download/view:	Download View

Download options

We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

	Seed (115)	Full (4673)	Representative proteomes				NCBI (3316)	Meta (2284)
	Seed (115)	Full (4673)	RP15 (368)	RP35 (712)	RP55 (952)	RP75 (1118)	NCBI (3316)	Meta (2284)
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.

Note: You can also download the data file for the tree.

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.

Curation

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

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:

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Species distribution

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How the sunburst is generated

The tree is built by considering the taxonomic lineage of each sequence that has a match to this family. For each node in the resulting tree, we draw an arc in the sunburst. The radius of the arc, its distance from the root node at the centre of the sunburst, shows the taxonomic level ("superkingdom", "kingdom", etc). The length of the arc represents either the number of sequences represented at a given level, or the number of species that are found beneath the node in the tree. The weighting scheme can be changed using the sunburst controls.

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Unmapped species names

The tree is built by looking at each sequence in the full alignment for the family. We take the name of the species given by UniProt and try to map that to the full taxonomic tree from NCBI. In some cases, the name chosen by UniProt does not map to any node in the NCBI tree, perhaps because the chosen name is listed as a synonym or a misspelling in the NCBI taxonomy.

So that these nodes are not simply omitted from the sunburst tree, we group them together in a separate branch (or segment of the sunburst tree). Since we cannot determine the lineage for these unmapped species, we show all levels between the superkingdom and the species as "uncategorised".

Sub-species

Since we reduce the species tree to only the eight main taxonomic levels, sequences that are mapped to the sub-species level in the tree would not normally be shown. Rather than leave out these species, we map them instead to their parent species. So, for example, for sequences belonging to one of the Vibrio cholerae sub-species in the NCBI taxonomy, we show them instead as belonging to the species Vibrio cholerae.

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For large species trees, you may see blank regions in the outer layers of the sunburst. These occur when there are large numbers of arcs to be drawn in a small space. If an arc is less than approximately one pixel wide, it will not be drawn and the space will be left blank. You may still be able to get some information about the species in that region by moving your mouse across the area, but since each arc will be very small, it will be difficult to accurately locate a particular species.

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Species trees

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Unfortunately we have found that there are problems viewing the interactive tree when the it becomes larger than a certain limit. Furthermore, we have found that Internet Explorer can become unresponsive when viewing some trees, regardless of their size. We therefore show a text representation of the species tree when the size is above a certain limit or if you are using Internet Explorer to view the site.

If you are using IE you can still load the interactive tree by clicking the "Generate interactive tree" button, but please be aware of the potential problems that the interactive species tree can cause.

Interactive tree

For all of the domain matches in a full alignment, we count the number that are found on all sequences in the alignment. This total is shown in the purple box.

We also count the number of unique sequences on which each domain is found, which is shown in green. Note that a domain may appear multiple times on the same sequence, leading to the difference between these two numbers.

Finally, we group sequences from the same organism according to the NCBI code that is assigned by UniProt, allowing us to count the number of distinct sequences on which the domain is found. This value is shown in the pink boxes.

We use the NCBI species tree to group organisms according to their taxonomy and this forms the structure of the displayed tree. Note that in some cases the trees are too large (have too many nodes) to allow us to build an interactive tree, but in most cases you can still view the tree in a plain text, non-interactive representation. Those species which are represented in the seed alignment for this domain are highlighted.

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Interactions

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

HPPK Pterin_bind

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.

Loading structure mapping...

Archea	Eukaryota
Bacteria	Other sequences
Viruses	Unclassified
Viroids	Unclassified sequence

Family: HPPK (PF01288)

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

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

[edit] Structural studies

[edit] References

[edit] Further reading

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

External database links

InterPro entry IPR000550

Gene Ontology

Domain organisation

Alignments

Alignment types

Viewing

Reformatting

Downloading

View options

Format an alignment

Download options

External links

HMM logo

Trees

Curation and family details

Curation

HMM information

Species distribution

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How the sunburst is generated

Colouring and labels

Anomalies in the taxonomy tree

Missing taxonomic levels

Unmapped species names

Sub-species

Too many species/sequences

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Species trees

Interactive tree

Interactions

Structures