EPSP synthase

Thus, the two substrates of this enzyme are phosphoenolpyruvate and 3-phospho-shikimate, whereas its two products are phosphate and 5-enolpyruvylshikimate-3-phosphate.

Nomenclature

The 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:3-phosphoshikimate 5-O-(1-carboxyvinyl)-transferase. Other names in common use include:

5-enolpyruvylshikimate-3-phosphate synthase,
3-enolpyruvylshikimate 5-phosphate synthase,
3-enolpyruvylshikimic acid-5-phosphate synthetase,
5'-enolpyruvylshikimate-3-phosphate synthase,
5-enolpyruvyl-3-phosphoshikimate synthase,
5-enolpyruvylshikimate-3-phosphate synthetase,
5-enolpyruvylshikimate-3-phosphoric acid synthase,
enolpyruvylshikimate phosphate synthase, and
3-phosphoshikimate 1-carboxyvinyl transferase.

Function

The enzyme participates in biosynthesis of the aromatic amino acids phenylalanine, tyrosine and tryptophan. The enzyme is a target for herbicides as these amino acids are only synthesized in plants and microorganisms. Glyphosate acts as a competitive inhibitor for phosphoenolpyruvate and is used as a broad-spectrum systemic herbicide.^[2]^[3]

Shikimate pathway

The shikimate pathway is a seven step metabolic route used by bacteria, fungi, and plants for the biosythesis of aromatic amino acids (phenylalanine, tyrosine, and tryptophan). The fourth aromatic amino acid tyrosine can be synthesized from phenylalanine. This pathway is not found in animals, hence the products of this pathway represent essential amino acids that must be obtained from the animal's diet.

Structure

EPSP synthase is a monomeric enzyme. It is composed of two domains, which are joined by protein strands. This strand acts as a hinge, and can bring the two protein domains closer together. When a substrate binds to the enzyme, ligand bonding causes the two parts of the enzyme to clamp down around the substrate in the active site.

Reaction

EPSP synthase catalyzes the reaction which converts shikimate-3-phosphate plus phosphoenolpyruvate to 5-enolpyruvylshikimate-3-phosphate (EPSP).

Applications

Herbicides

Glyphosate is a chemical herbicide which kills plants by inhbiting the shikimate pathway. It targets EPSP synthase, the enzyme that catalyzes the conversion of shikimate-3-phosphate and phosphoenolpyruvate into EPSP. Glyphosate is a competitive inhibitor of the enzyme. Glyphosate resembles the transition state that transforms the reactants into products in the reaction that is catalyzed by EPSP synthase. Hence glyphosate (as a transition state analog) binds more tightly to EPSP synthase than its natural substrate and thereby prevents binding of substrate to the enzyme.^[2]

This binding leads to the inhibition of the enzyme, and consequently shuts down the entire pathway. Since plants require the shikimate pathway to produce aromatic amino acids, this kills the plant. This also means that glyphosate is generally harmless to animals and humans, since they are not dependent on the shikimate pathway for the synthesis of Phe, Trp, and Tyr and instead obtain these amino acids from their diet.

References

↑ Priestman MA, Healy ML, Funke T, Becker A, Schönbrunn E (October 2005). "Molecular basis for the glyphosate-insensitivity of the reaction of 5-enolpyruvylshikimate 3-phosphate synthase with shikimate". FEBS Lett. 579 (25): 5773–80. doi:10.1016/j.febslet.2005.09.066. PMID 16225867.
↑ 2.0 2.1 Schönbrunn E, Eschenburg S, Shuttleworth WA, Schloss JV, Amrhein N, Evans JN, Kabsch W (February 2001). "Interaction of the herbicide glyphosate with its target enzyme 5-enolpyruvylshikimate 3-phosphate synthase in atomic detail". Proc. Natl. Acad. Sci. U.S.A. 98 (4): 1376–80. doi:10.1073/pnas.98.4.1376. PMC 29264. PMID 11171958.
↑ Pollegioni L, Schonbrunn E, Siehl D (August 2011). "Molecular basis of glyphosate resistance-different approaches through protein engineering". FEBS J. 278 (16): 2753–66. doi:10.1111/j.1742-4658.2011.08214.x. PMID 21668647.