3-Deoxy-D-arabinoheptulosonate 7-phosphate (DAHP) synthase (EC2.5.1.54) is the first enzyme in a series of metabolicreactions known as the shikimate pathway, which is responsible for the biosynthesis of the amino acidsphenylalanine, 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.
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.
This is the reaction catalyzed by DAHP synthase.
Structure
This image shows the quaternary structure of DAHP synthase.This image shows the quaternary structure of DAHP synthase, with the secondary and tertiary structures illustrated in cartoon form.
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.
Shikimic acid, more commonly known as its anionic form shikimate, is a cyclohexene, a cyclitol and a cyclohexanecarboxylic acid. It is an important biochemical metabolite in plants and microorganisms. Its name comes from the Japanese flower shikimi, from which it was first isolated in 1885 by Johan Fredrik Eykman. The elucidation of its structure was made nearly 50 years later.
Phosphoenolpyruvate is the ester derived from the enol of pyruvate and phosphate. It exists as an anion. PEP is an important intermediate in biochemistry. It has the highest-energy phosphate bond found in organisms, and is involved in glycolysis and gluconeogenesis. In plants, it is also involved in the biosynthesis of various aromatic compounds, and in carbon fixation; in bacteria, it is also used as the source of energy for the phosphotransferase system.
Amino acid synthesis is the set of biochemical processes by which the amino acids are produced. The substrates for these processes are various compounds in the organism's diet or growth media. Not all organisms are able to synthesize all amino acids. For example, humans can synthesize 11 of the 20 standard amino acids. These 11 are called the non-essential amino acids).
Erythrose 4-phosphate is a phosphate of the simple sugar erythrose. It is an intermediate in the pentose phosphate pathway and the Calvin cycle.
In enzymology, a phosphoribosylanthranilate isomerase (PRAI) is an enzyme that catalyzes the third step of the synthesis of the amino acid tryptophan.
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The enzyme chorismate synthase catalyzes the chemical reaction
The enzyme methylglyoxal synthase catalyzes the chemical reaction
In enzymology, a 3-deoxy-8-phosphooctulonate synthase (EC 2.5.1.55) is an enzyme that catalyzes the chemical reaction
Shikimate kinase (EC 2.7.1.71) is an enzyme that catalyzes the ATP-dependent phosphorylation of shikimate to form shikimate 3-phosphate. This reaction is the fifth step of the shikimate pathway, which is used by plants and bacteria to synthesize the common precursor of aromatic amino acids and secondary metabolites. The systematic name of this enzyme class is ATP:shikimate 3-phosphotransferase. Other names in common use include shikimate kinase (phosphorylating), and shikimate kinase II.
The Aminoshikimate pathway is a biochemical pathway present in some plants, which has been studied by biologists, biochemists and especially those interested in manufacture of novel antibiotic drugs. The pathway is a novel variation of the shikimate pathway. The aminoshikimate pathway was first discovered and studied in the rifamycin B producer Amycolatopsis mediterranei. Its end product, 3-amino-5-hydroxybenzoate, serves as an initiator for polyketide synthases in the biosynthesis of ansamycins.
In enzymology, the committed step is an effectively irreversible enzymatic reaction that occurs at a branch point during the biosynthesis of some molecules. As the name implies, after this step, the molecules are "committed" to the pathway and will ultimately end up in the pathway's final product. The first committed step should not be confused with the rate-determining step, which is the slowest step in a reaction or pathway. However, it is sometimes the case that the first committed step is in fact the rate-determining step as well.
5-enolpyruvylshikimate-3-phosphate (EPSP) synthase is an enzyme produced by plants and microorganisms. EPSPS catalyzes the chemical reaction:
3-Deoxy-D-arabino-heptulosonic acid 7-phosphate (DAHP) is a 7-carbon ulonic acid. This compound is found in the shikimic acid biosynthesis pathway and is an intermediate in the production of aromatic amino acids.
1 2 3 4 5 Schoner R, Herrmann KM (September 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): 5440–7. PMID9387.
1 2 3 Stephens CM, Bauerle R (November 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): 20810–7. PMID1682314.
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