This entry represents 5-enolpyruvylshikimate-3-phosphate (EPSP) synthase (also known as 3-phosphoshikimate 1-carboxyvinyltransferase), catalyses the sixth step in the biosynthesis from chorismate of the aromatic amino acids (the shikimate pathway) in bacteria (gene aroA), plants and fungi (where it is part of a multifunctional enzyme which catalyses five consecutive steps in this pathway) [1]. The sixth step is the formation of EPSP and inorganic phosphate from shikimate-3-phosphate (S3P) and phosphoenolpyruvate (PEP).

EPSP can use shikimate or shikimate-3-phosphate as a substrate. By binding shikimate, the backbone of the active site is changed, which affects the binding of glyphosate and renders the reaction insensitive to inhibition by glyphosate [2]. On isolation of the discontinuous C-terminal domain, it was found that it binds neither its substrate nor its inhibitor but maintains structural integrity [3].

Earlier studies suggested that the active site of the enzyme is in the cleft between its two globular domains. When the enzyme binds S3P, there is a conformational change in the isolated N-terminal domain [4]. The sequence of EPSP from various biological sources shows that the structure of the enzyme has been well conserved throughout evolution. Two strongly conserved regions are well defined. The first one corresponds to a region that is part of the active site and which is also important for the resistance to glyphosate [5]. The second second one is located in the C-terminal part of the protein and contains a conserved lysine which seems to be important for the activity of the enzyme.

Since the shikimate pathway is not present in vertebrates but is essential for the life of plants, fungi and bacteria, it is commonly viewed as a target for antimicrobial drug development.

1. Structure and topological symmetry of the glyphosate target 5-enolpyruvylshikimate-3-phosphate synthase: a distinctive protein fold. Proc. Natl. Acad. Sci. U.S.A. 88, 5046-50
2. Molecular basis for the glyphosate-insensitivity of the reaction of 5-enolpyruvylshikimate 3-phosphate synthase with shikimate. FEBS Lett. 579, 5773-80
3. Engineering and characterization of the isolated C-terminal domain of 5-enolpyruvylshikimate-3-phosphate (EPSP) synthase. J. Microbiol. Biotechnol. 17, 1385-9
4. Shikimate-3-phosphate binds to the isolated N-terminal domain of 5-enolpyruvylshikimate-3-phosphate synthase. Biochemistry 40, 3951-7
5. Site-directed mutagenesis of a conserved region of the 5-enolpyruvylshikimate-3-phosphate synthase active site. J. Biol. Chem. 266, 22364-9

This entry represents 5-enolpyruvylshikimate-3-phosphate (EPSP) synthase (also known as 3-phospho
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