3-Deoxy-D-arabinoheptulosonate 7-phosphate (DAHP) synthase () is the first enzyme in a series of

metabolic Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cel ...

reactions known as the shikimate pathway, which is responsible for the biosynthesis of the amino acids

phenylalanine Phenylalanine (symbol Phe or F) is an essential α-amino acid with the formula . It can be viewed as a benzyl group substituted for the methyl group of alanine, or a phenyl group in place of a terminal hydrogen of alanine. This essential amino a ...

tyrosine -Tyrosine or tyrosine (symbol Tyr or Y) or 4-hydroxyphenylalanine is one of the 20 standard amino acids that are used by cells to synthesize proteins. It is a non-essential amino acid with a polar side group. The word "tyrosine" is from the Gr ...

, and

tryptophan Tryptophan (symbol Trp or W) is an α-amino acid that is used in the biosynthesis of proteins. Tryptophan contains an α-amino group, an α-carboxylic acid group, and a side chain indole, making it a polar molecule with a non-polar aromati ...

. 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. 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 () is an

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different molecule ...

that catalyzes the

chemical reaction A chemical reaction is a process that leads to the chemical transformation of one set of chemical substances to another. Classically, chemical reactions encompass changes that only involve the positions of electrons in the forming and break ...

:phosphoenolpyruvate + D-erythrose 4-phosphate + H₂O

\rightleftharpoons

3-deoxy-D-arabino-hept-2-ulosonate 7-phosphate + phosphate The three substrates of this enzyme are

phosphoenolpyruvate Phosphoenolpyruvate (2-phosphoenolpyruvate, PEP) 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 (−61.9 kJ/ ...

D-erythrose 4-phosphate 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 addition, it serves as a precursor in the biosynthesis of the aromatic amino acids tyrosine, p ...

, and H₂O, whereas its two products are 3-deoxy-D-arabino-hept-2-ulosonate 7-phosphate and

phosphate In chemistry, a phosphate is an anion, salt, functional group or ester derived from a phosphoric acid. It most commonly means orthophosphate, a derivative of orthophosphoric acid . The phosphate or orthophosphate ion is derived from phosph ...

Nomenclature

This enzyme belongs to the family of

transferase A transferase is any one of a class of enzymes that catalyse the transfer of specific functional groups (e.g. a methyl or glycosyl group) from one molecule (called the donor) to another (called the acceptor). They are involved in hundreds of ...

s, to be specific those transferring aryl or alkyl groups other than methyl groups. The

systematic name A systematic name is a name given in a systematic way to one unique group, organism, object or chemical substance, out of a specific population or collection. Systematic names are usually part of a nomenclature. A semisystematic name or semitrivial ...

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

and D-erythrose 4-phosphate to DAHP and

. 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. 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. In ''

Escherichia coli ''Escherichia coli'' (),Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. also known as ''E. coli'' (), is a Gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus '' Esc ...

'', a species of bacteria, DAHP synthase is found as three

isoenzymes In biochemistry, isozymes (also known as isoenzymes or more generally as multiple forms of enzymes) are enzymes that differ in amino acid sequence but catalyze the same chemical reaction. Isozymes usually have different kinetic parameters (e.g. dif ...

, each of which sensitive to one of the amino acids produced in the shikimate pathway. 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

, 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. 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

and noncompetitive inhibition with respect to D-erythrose 4-phosphate. Studies of product inhibition have shown that

is the first substrate to bind to the enzyme complex, inorganic

is the first product to dissociate from the enzyme complex. 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. This method is also found in bacteria, but feedback inhibition is more prevalent. In plants, as the plants progressed through the growth cycle, the activity of DAHP synthase changed.

Catalytic activity

Metal ions are required in order for DAHP synthase to catalyze reactions. In DAHP synthase, it has been shown that binding site contains patterns of

cysteine Cysteine (symbol Cys or C; ) is a semiessential proteinogenic amino acid with the formula . The thiol side chain in cysteine often participates in enzymatic reactions as a nucleophile. When present as a deprotonated catalytic residue, s ...

and

histidine Histidine (symbol His or H) is an essential amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated –NH3+ form under biological conditions), a carboxylic acid group (which is in the ...

residues bound to metal ions in a Cys-X-X-His fashion. It has been shown that, in general, DAHP synthases require a bivalent metal ion cofactor in order for the enzyme to function properly. Metal ions that can function as cofactors include Mn²⁺, Fe²⁺, Co²⁺, Zn²⁺, Cu²⁺, and Ca²⁺. Studies have suggested that one metal ion bonds to each monomer of DAHP synthase. 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 A tetramer () (''tetra-'', "four" + '' -mer'', "parts") is an oligomer formed from four monomers or subunits. The associated property is called ''tetramery''. An example from inorganic chemistry is titanium methoxide with the empirical formula T ...

. 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 , , , and .

Nomenclature

Biological function

Catalytic activity

Structure

Structural studies

References

Further reading