Summary: DAHP synthetase I family
Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.
This is the Wikipedia entry entitled "DAHP synthase". More...
DAHP synthase Edit Wikipedia article
| 3-deoxy-7-phosphoheptulonate synthase | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||
| EC number | 2.5.1.54 | ||||||||
| CAS number | 9026-94-2 | ||||||||
| 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 | ||||||||
|
|||||||||
| DAHP synthetase I domain | |||||||||
|---|---|---|---|---|---|---|---|---|---|
Structure of Aquifex aeolicus kdo8ps in complex with z-methyl-pep 2-dehydro-3-deoxyphosphooctonate aldolase.[1]
|
|||||||||
| Identifiers | |||||||||
| Symbol | DAHP_synth_1 | ||||||||
| Pfam | PF00793 | ||||||||
| Pfam clan | CL0036 | ||||||||
| InterPro | IPR006218 | ||||||||
| SCOP | 51569 | ||||||||
| SUPERFAMILY | 51569 | ||||||||
|
|||||||||
3-Deoxy-D-arabinoheptulosonate 7-phosphate (DAHP) synthase (EC 2.5.1.54) is the first enzyme in a series of metabolic reactions known as the shikimate pathway, which is responsible for the biosynthesis of the amino acids phenylalanine, tyrosine, and tryptophan. Since it is the first enzyme in the shikimate pathway, it controls the amount of carbon entering the pathway. Enzyme inhibition is the primary method of regulating the amount of carbon entering the pathway.[2] Forms of this enzyme differ between organisms, but can be considered DAHP synthase based upon the reaction that is catalyzed by this enzyme.
In enzymology, a DAHP synthase (EC 2.5.1.54) is an enzyme that catalyzes the chemical reaction
- phosphoenolpyruvate + D-erythrose 4-phosphate + H2O 3-deoxy-D-arabino-hept-2-ulosonate 7-phosphate + phosphate
The three substrates of this enzyme are phosphoenolpyruvate, D-erythrose 4-phosphate, and H2O, whereas its two products are 3-deoxy-D-arabino-hept-2-ulosonate 7-phosphate and phosphate.
Contents
Nomenclature
This enzyme belongs to the family of transferases, to be specific those transferring aryl or alkyl groups other than methyl groups. The systematic name of this enzyme class is phosphoenolpyruvate:D-erythrose-4-phosphate C-(1-carboxyvinyl)transferase (phosphate-hydrolysing, 2-carboxy-2-oxoethyl-forming). Other names in common use include 2-dehydro-3-deoxy-phosphoheptonate aldolase, 2-keto-3-deoxy-D-arabino-heptonic acid 7-phosphate synthetase, 3-deoxy-D-arabino-2-heptulosonic acid 7-phosphate synthetase, 3-deoxy-D-arabino-heptolosonate-7-phosphate synthetase, 3-deoxy-D-arabino-heptulosonate 7-phosphate synthetase, 7-phospho-2-keto-3-deoxy-D-arabino-heptonate D-erythrose-4-phosphate, lyase (pyruvate-phosphorylating), 7-phospho-2-dehydro-3-deoxy-D-arabino-heptonate, D-erythrose-4-phosphate lyase (pyruvate-phosphorylating), D-erythrose-4-phosphate-lyase, D-erythrose-4-phosphate-lyase (pyruvate-phosphorylating), DAH7-P synthase, DAHP synthase, DS-Co, DS-Mn, KDPH synthase, KDPH synthetase, deoxy-D-arabino-heptulosonate-7-phosphate synthetase, phospho-2-dehydro-3-deoxyheptonate aldolase, phospho-2-keto-3-deoxyheptanoate aldolase, phospho-2-keto-3-deoxyheptonate aldolase, phospho-2-keto-3-deoxyheptonic aldolase, and phospho-2-oxo-3-deoxyheptonate aldolase.
Biological function
The primary function of DAHP synthase is to catalyze the reaction of phosphoenolpyruvate and D-erythrose 4-phosphate to DAHP and phosphate. However, another biological function of the enzyme is to regulate the amount of carbon that enters the shikimate pathway. This is accomplished primarily through two different methods, feedback inhibition and transcriptional control.[2] Feedback inhibition and transcriptional control are both mechanisms of regulating carbon in bacteria, but the only mechanism of regulation found in DAHP synthase found in plants is transcriptional control.[2]
In Escherichia coli, a species of bacteria, DAHP synthase is found as three isoenzymes, each of which sensitive to one of the amino acids produced in the shikimate pathway.[3] In a study of DAHP synthase sensitive to tyrosine in E. coli, it was determined that the enzyme is inhibited by tyrosine through noncompetitive inhibition with respect to phosphoenolpyruvate, the first substrate of the reaction catalyzed by DAHP synthase, while the enzyme is inhibited by tyrosine through competitive inhibition with respect to D-erythrose 4-phosphate, the second substrate of the reaction catalyzed by DAHP synthase when the concentration of tyrosine is above 10 μM.[3] It was also determined that the enzyme is inhibited by inorganic phosphate through noncompetitive inhibition with respect to both substrates and inhibited by DAHP through competitive inhibition with respect to phosphoenolpyruvate and noncompetitive inhibition with respect to D-erythrose 4-phosphate.[3] Studies of product inhibition have shown that phosphoenolpyruvate is the first substrate to bind to the enzyme complex, inorganic phosphate is the first product to dissociate from the enzyme complex.[3] Thus the amount of carbon entering the shikimate pathway can be controlled by inhibiting DAHP synthase from catalyzing the reaction that forms DAHP.
Carbon flow into the shikimate pathway in plants is regulated by transcriptional control.[3] This method is also found in bacteria, but feedback inhibition is more prevalent.[2] In plants, as the plants progressed through the growth cycle, the activity of DAHP synthase changed.[2]
Catalytic activity
Metal ions are required in order for DAHP synthase to catalyze reactions.[2] In DAHP synthase, it has been shown that binding site contains patterns of cysteine and histidine residues bound to metal ions in a Cys-X-X-His fashion.[2]
It has been shown that, in general, DAHP synthases require a bivalent metal ion cofactor in order for the enzyme to function properly.[4] Metal ions that can function as cofactors include Mn2+, Fe2+, Co2+, Zn2+, Cu2+, and Ca2+.[4] Studies have suggested that one metal ion bonds to each monomer of DAHP synthase.[4]
The reaction catalyzed by DAHP synthase is shown below.
Structure
The quaternary structure of DAHP synthase consists of two tightly bound dimers, which means that DAHP synthase is a tetramer.[5]
To the right is an image of DAHP synthase that shows the quaternary structure of DAHP synthase. This image shows that DAHP synthase consists of two tightly bound dimers. Each of the monomer chains is colored differently.
Below the first image to the right is an image of DAHP synthase that also shows quaternary structure, however this image is in a cartoon view. This view also shows each of the four monomers colored differently. In addition, this view can also be used to show secondary and tertiary structures. As shown, two of the monomers have beta sheets that interact on one side of the enzyme, while the other two monomers have beta sheets that interact on the opposite side.
Structural studies
As of late 2007, four structures have been solved for this class of enzymes, with PDB accession codes 1RZM, 1VR6, 1VS1, and 2B7O.
| Class-II DAHP synthetase family | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||
| Symbol | DAHP_synth_2 | ||||||||
| Pfam | PF01474 | ||||||||
| Pfam clan | CL0036 | ||||||||
| InterPro | IPR002480 | ||||||||
|
|||||||||
References
- ^ Xu X; Wang J; Grison C; Petek S; Coutrot P; Birck MR; et al. (2003). "Structure-based design of novel inhibitors of 3-deoxy-D-manno-octulosonate 8-phosphate synthase.". Drug Des Discov. 18 (2-3): 91–9. PMID 14675946. doi:10.3109/10559610290271787.
- ^ a b c d e f g Herrmann, K.; Entus, R. (2001). "Shikimate Pathway: Aromatic Amino Acids and Beyond". Encyclopedia of Life Sciences. ISBN 0470016175. doi:10.1038/npg.els.0001315.
- ^ a b c d e Schoner, R.; Herrmann, K. M. (1976). "3-Deoxy-D-arabino-heptulosonate 7-phosphate synthase. Purification, properties, and kinetics of the tyrosine-sensitive isoenzyme from Escherichia coli". The Journal of Biological Chemistry. 251 (18): 5440–5447. PMID 9387.
- ^ a b c Stephens, C. M.; Bauerle, R. (1991). "Analysis of the metal requirement of 3-deoxy-D-arabino-heptulosonate-7-phosphate synthase from Escherichia coli". The Journal of Biological Chemistry. 266 (31): 20810–20817. PMID 1682314.
- ^ Shumilin, I. A.; Kretsinger, R. H.; Bauerle, R. H. (1999). "Crystal structure of phenylalanine-regulated 3-deoxy-D-arabino-heptulosonate-7-phosphate synthase from Escherichia coli". Structure. 7 (7): 865–875. PMID 10425687. doi:10.1016/S0969-2126(99)80109-9.
Further reading
- Srinivasan PR & Sprinson DB (1959). "2-Keto-3-deoxy-D-arabo-heptonic acid 7-phosphate synthetase". J. Biol. Chem. 234 (4): 716–722. PMID 13654249.
- Jossek R; Bongaerts J; Sprenger GA (2001). "Characterization of a new feedback-resistant 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase AroF of Escherichia coli". FEMS Microbiol. Lett. 202 (1): 145–8. PMID 11506923. doi:10.1111/j.1574-6968.2001.tb10795.x.
- Schneider TR; Hartmann M; Braus GH (September 1999). "Crystallization and preliminary X-ray analysis of 3-deoxy-D-arabino-heptulosonate-7-phosphate synthase (tyrosine inhibitable) from Saccharomyces cerevisiae". Acta Crystallogr. D. 55 (Pt 9): 1586–8. PMID 10489454. doi:10.1107/S0907444999007830.
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.
DAHP synthetase I family Provide feedback
Members of this family catalyse the first step in aromatic amino acid biosynthesis from chorismate. E-coli has three related synthetases, which are inhibited by different aromatic amino acids. This family also includes KDSA which has very similar catalytic activity but is involved in the first step of liposaccharide biosynthesis. The enzyme is also part of the shikimate pathway, EC:2.5.1.54.
Literature references
-
Shumilin IA, Kretsinger RH, Bauerle RH; , Structure Fold Des 1999;7:865-875.: Crystal structure of phenylalanine-regulated 3-deoxy-D-arabino-heptulosonate-7-phosphate synthase from Escherichia coli. PUBMED:10425687 EPMC:10425687
Internal database links
| SCOOP: | NeuB |
External database links
| HOMSTRAD: | DAHP_synth_1 |
| SCOP: | 1qr7 |
This tab holds annotation information from the InterPro database.
InterPro entry IPR006218
Members of the 3-deoxy-D-arabino-heptulosonate 7-phosphate (DAHP) synthetase family catalyse the first step in aromatic amino acid biosynthesis from chorismate. Class I includes bacterial and yeast enzymes; class II includes higher plants and various microorganisms (see INTERPRO) [PUBMED:8760910].The first step in the common pathway leading to the biosynthesis of aromatic compounds is the stereospecific condensation of phosphoenolpyruvate (PEP) and D-erythrose-4-phosphate (E4P) giving rise to 3-deoxy-D-arabino-heptulosonate-7-phosphate (DAHP). This reaction is catalyzed by DAHP synthase, a metal-activated enzyme, which in microorganisms is the target for negative-feedback regulation by pathway intermediates or by end products. In Escherichia coli there are three DAHP synthetase isoforms, each specifically inhibited by one of the three aromatic amino acids. The crystal structure of the phenylalanine-regulated form of DAHP synthetase shows the fold as is a (beta/alpha)8 barrel with several additional beta strands and alpha helices [PUBMED:10425687].
Gene Ontology
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
| Biological process | biosynthetic process (GO:0009058) |
Domain organisation
Below is a listing of the unique domain organisations or architectures in which this domain is found. More...
Loading domain graphics...
Pfam Clan
This family is a member of clan TIM_barrel (CL0036), which has the following description:
This large superfamily of TIM barrel enzymes all contain a common phosphate binding site. The phosphate is found in a variety of cofactors and ligands such as FMN [1,2].
The clan contains the following 59 members:
4HFCP_synth Ala_racemase_N ALAD Aldolase AP_endonuc_2 BtpA CdhD ComA CutC DAHP_synth_1 DAHP_synth_2 DeoC DHDPS DHO_dh DHquinase_I DUF2090 DUF561 DUF692 DUF993 Dus F_bP_aldolase FMN_dh G3P_antiterm Glu_syn_central Glu_synthase His_biosynth HMGL-like IGPS IMPDH KDGP_aldolase Lys-AminoMut_A MtrH NanE NAPRTase NeuB NMO OAM_alpha OMPdecase Orn_Arg_deC_N Oxidored_FMN PcrB PdxJ PRAI PRMT5_TIM Pterin_bind QRPTase_C Radical_SAM RhaA Ribul_P_3_epim SOR_SNZ Tagatose_6_P_K TAL_FSA ThiC_Rad_SAM ThiG TIM TMP-TENI Trp_syntA UvdE UxuAAlignments
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 (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the UniProtKB sequence database, the NCBI sequence database, and our metagenomics sequence database. More...
View options
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 (20) |
Full (7270) |
Representative proteomes | UniProt (22927) |
NCBI (32921) |
Meta (4253) |
||||
|---|---|---|---|---|---|---|---|---|---|
| RP15 (1446) |
RP35 (4132) |
RP55 (7100) |
RP75 (11607) |
||||||
| Jalview | |||||||||
| HTML | |||||||||
| PP/heatmap | 1 | ||||||||
1Cannot generate PP/Heatmap alignments for seeds; no PP data available
Key:
available,
not generated,
— not available.
Format an alignment
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 (20) |
Full (7270) |
Representative proteomes | UniProt (22927) |
NCBI (32921) |
Meta (4253) |
||||
|---|---|---|---|---|---|---|---|---|---|
| RP15 (1446) |
RP35 (4132) |
RP55 (7100) |
RP75 (11607) |
||||||
| Raw Stockholm | |||||||||
| Gzipped | |||||||||
You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.
HMM logo
HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...
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: | Pfam-B_1032 (release 2.1) |
| Previous IDs: | DAHP_synthetase; |
| Type: | Domain |
| Author: | Bateman A, Griffiths-Jones SR |
| Number in seed: | 20 |
| Number in full: | 7270 |
| Average length of the domain: | 279.70 aa |
| Average identity of full alignment: | 28 % |
| Average coverage of the sequence by the domain: | 84.86 % |
HMM information
| HMM build commands: |
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 26740544 -E 1000 --cpu 4 HMM pfamseq
|
||||||||||||
| Model details: |
|
||||||||||||
| Model length: | 275 | ||||||||||||
| Family (HMM) version: | 19 | ||||||||||||
| Download: | download the raw HMM for this family |
Species distribution
Sunburst controls
HideWeight segments by...
Change the size of the sunburst
Colour assignments
Archea
|
Eukaryota
|
Bacteria
|
Other sequences
|
Viruses
|
Unclassified
|
Viroids
|
Unclassified sequence
|
Selections
Align selected sequences to HMM
Generate a FASTA-format file
Clear selection
This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the adjacent tab. More...
Tree controls
HideThe tree shows the occurrence of this domain across different species. More...
Loading...
Please note: for large trees this can take some time. While the tree is loading, you can safely switch away from this tab but if you browse away from the family page entirely, the tree will not be loaded.
Interactions
There is 1 interaction for this family. More...
DAHP_synth_1Structures
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 DAHP_synth_1 domain has been found. There are 417 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...