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. (wikipedia.org)
Since it is the first enzyme in the shikimate pathway, it controls the amount of carbon entering the pathway. (wikipedia.org)
However, another biological function of the enzyme is to regulate the amount of carbon that enters the shikimate pathway. (wikipedia.org)
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. (wikipedia.org)
Thus the amount of carbon entering the shikimate pathway can be controlled by inhibiting DAHP synthase from catalyzing the reaction that forms DAHP. (wikipedia.org)
Carbon flow into the shikimate pathway in plants is regulated by transcriptional control. (wikipedia.org)
Since it catalyzes the second key step in the shikimate pathway, which is crucial for the aromatic amino acid metabolism in bacteria, fungi, and plants, but not in mammals, DHQS is a potential target for new antimicrobial agents, anti-parasitic agents and herbicides. (nih.gov)
The first common step in biosynthesis for these amino acids follows the shikimate pathway and the initial reaction, the condensation of erythrose-4-phosphate (E4P) and phosphoenolpyruvate (PEP) is catalyzed by the enzyme family of 3-Deoxy-arabino-heptulosonate-7-phosphate synthases (DAHP synthases). (uni-goettingen.de)
Biosynthesis2
When the cells were stimulated in the presence of 2,4-diamino-6-hydroxypyrimidine (DAHP), an inhibitor of BH4 biosynthesis, biopterin levels decreased by 90% within 6 hr, whereas nitrite production was essentially unaffected. (aspetjournals.org)
For the typical bacterium that can make all 20 amino acids, there are 1-2 gaps in amino acid biosynthesis pathways. (lbl.gov)
1.541
In enzymology, a DAHP synthase (EC 2.5.1.54) is an enzyme that catalyzes the chemical reaction phosphoenolpyruvate + D-erythrose 4-phosphate + H2O ⇌ {\displaystyle \rightleftharpoons } 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. (wikipedia.org)
Isoenzymes1
These isoenzymes require a divalent metal ion and most of them are feedback regulated by the respective end product.This thesis describes studies on crystal structures of the tyrosine regulated DAHP synthase from Saccharomyces cerevisiae and a variety of its complexes. (uni-goettingen.de)
Tyrosine2
A complex of DAHP synthase, manganese(II) and tyrosine reveals the effector binding pocket of this enzyme family. (uni-goettingen.de)
By comparing the active and the inhibited structures of the enzyme the inhibition mechanism of the tyrosine sensitive DAHP synthase could be understood. (uni-goettingen.de)
Bacteria2
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. (wikipedia.org)
For diverse bacteria and archaea that can utilize a carbon source, there is a complete high-confidence catabolic pathway (including a transporter) just 38% of the time, and there is a complete medium-confidence pathway 63% of the time. (lbl.gov)
Inhibition4
Enzyme inhibition is the primary method of regulating the amount of carbon entering the pathway. (wikipedia.org)
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. (wikipedia.org)
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. (wikipedia.org)
This inhibition could be reversed by loading the cells with dihydrobiopterin, a precursor of BH4 via the dihydrofolate reductase salvage pathway. (aspetjournals.org)
Organisms1
Forms of this enzyme differ between organisms, but can be considered DAHP synthase based upon the reaction that is catalyzed by this enzyme. (wikipedia.org)
Reaction2
The primary function of DAHP synthase is to catalyze the reaction of phosphoenolpyruvate and D-erythrose 4-phosphate to DAHP and phosphate. (wikipedia.org)
The reaction catalyzed by DAHP synthase is shown below. (wikipedia.org)
Metal ion2
It has been shown that, in general, DAHP synthases require a bivalent metal ion cofactor in order for the enzyme to function properly. (wikipedia.org)
Studies have suggested that one metal ion bonds to each monomer of DAHP synthase. (wikipedia.org)
Phosphoenolpyruvate1
The systematic name of this enzyme class is phosphoenolpyruvate:D-erythrose-4-phosphate C-(1-carboxyvinyl)transferase (phosphate-hydrolysing, 2-carboxy-2-oxoethyl-forming). (wikipedia.org)
Structures1
As of late 2007, four structures have been solved for this class of enzymes, with PDB accession codes 1RZM, 1VR6, 1VS1, and 2B7O. (wikipedia.org)
Complex1
The binding pockets for both substrates could be determined on the basis of the double complex of the DAHP synthase with manganese, PEP and the E4P analogue glyceraldehyde-3-phosphate (G3P). (uni-goettingen.de)
Plants1
In plants, as the plants progressed through the growth cycle, the activity of DAHP synthase changed. (wikipedia.org)
Active1
The results presented here support previous suggestions, based on experiments with isolated enzymes, that BH4 is absolutely required for cytokine-stimulated nitric oxide production in macrophages and they suggest that only a small fraction of the total intracellular BH4 pool in macrophages is utilized in the production of fully active nitric oxide synthase. (aspetjournals.org)
Family1
This enzyme belongs to the family of transferases, to be specific those transferring aryl or alkyl groups other than methyl groups. (wikipedia.org)
Step1
Candidates for each step are identified by using ublast (a fast alternative to protein BLAST) against a database of manually-curated proteins (most of which are experimentally characterized) or by using HMMer with enzyme models (usually from TIGRFam ). (lbl.gov)
Shikimate pathway7
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. (wikipedia.org)
Since it is the first enzyme in the shikimate pathway, it controls the amount of carbon entering the pathway. (wikipedia.org)
However, another biological function of the enzyme is to regulate the amount of carbon that enters the shikimate pathway. (wikipedia.org)
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. (wikipedia.org)
Thus the amount of carbon entering the shikimate pathway can be controlled by inhibiting DAHP synthase from catalyzing the reaction that forms DAHP. (wikipedia.org)
Carbon flow into the shikimate pathway in plants is regulated by transcriptional control. (wikipedia.org)
Chorismate Is Synthesized from PEP and Erythrose-4-P. Chorismate biosynthesis occurs via the shikimate pathway (Figure 25.36). (catsboard.com)
Metabolic2
The DAHP synthases are possible targets for fungicides and represent a model system for feedback regulation in metabolic pathways. (rcsb.org)
The precursors for this pathway are the common metabolic intermediates phosphoenolpyruvate and erythrose-4-phosphate. (catsboard.com)
As a model system, Arabidopsis has helped to elucidate many details of the phenylpropanoid pathway, its enzymes and intermediates, and the interconnectedness of the pathway with plant metabolism as a whole. (bioone.org)
Metal ions are required in order for DAHP synthase to catalyze reactions. (wikipedia.org)
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. (wikipedia.org)
To gain further insight into the role of the metal ion and the catalytic mechanism in general, the crystal structures of several complexes between the tyrosine-regulated form of DAHP synthase from Saccharomyces cerevisiae and different metal ions and ligands have been determined. (rcsb.org)
Regulation1
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. (wikipedia.org)
Crystal structure1
The site and binding mode of E4P was derived from the 1.5A resolution crystal structure of DAHP synthase in complex with PEP, Co2+, and the E4P analogue glyceraldehyde 3-phosphate. (rcsb.org)