EPSP synthase

Function

5-enolpyruvylshikimate 3-phosphate (EPSP) synthase is a key enzyme for the biosynthesis of aromatic amino acids in plants and many microbes. EPSP synthase catalyzes the addition of phosphoenol pyruvate (PEP) to shikimate-3-phosphate (S3P), generating 5-enolpyruvylshikimate-3-phosphate, which is a precursor for phenylalanine and tyrosine^[1]. EPSP synthase is a target for herbicides like Roundup, which contain glyphosate, an inhibitor of EPSP synthase. Herbicide resistant plants contain an glyphosate insensitive version of EPSP synthase derived from Agrobacterium sp strain CP4, so it is called CP4 EPSP synthase. ^[2],

Structural insights

The enzyme has two domains, with the active site found in the interdomain cleft . There is a substantial structural change upon substrate binding, resulting in a conformation. . Glyphosate (also known as Roundup) occupies the of the second substrate, phosphoenol pyruvate ^[3]. Interestingly CP4 EPSP synthase still binds glyphosate in the absence of PEP, but a conformational change in glyphosate to accommodate a steric clash with shortens the length of glyphosate, from 7.3 angstroms to 6.67 angstroms, and changes the IC50 by a factor of over 4,000, from 2.5 micromolar to 11 millimolar.

3D structures of EPSP synthase

EPSP synthase 3D structures

Structure of E. coli EPSP synthase complex with shikimate-3-phosphate, the herbicide glyphosate and formic acid (PDB entry 1g6s)

Drag the structure with the mouse to rotate

ReferencesReferences

↑ Priestman MA, Healy ML, Funke T, Becker A, Schonbrunn E. Molecular basis for the glyphosate-insensitivity of the reaction of 5-enolpyruvylshikimate 3-phosphate synthase with shikimate. FEBS Lett. 2005 Oct 24;579(25):5773-80. PMID:16225867 doi:10.1016/j.febslet.2005.09.066
↑ Funke T, Han H, Healy-Fried ML, Fischer M, Schonbrunn E. Molecular basis for the herbicide resistance of Roundup Ready crops. Proc Natl Acad Sci U S A. 2006 Aug 29;103(35):13010-5. Epub 2006 Aug 17. PMID:16916934
↑ Schonbrunn E, Eschenburg S, Shuttleworth WA, Schloss JV, Amrhein N, Evans JN, Kabsch W. Interaction of the herbicide glyphosate with its target enzyme 5-enolpyruvylshikimate 3-phosphate synthase in atomic detail. Proc Natl Acad Sci U S A. 2001 Feb 13;98(4):1376-80. PMID:11171958 doi:http://dx.doi.org/10.1073/pnas.98.4.1376

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[1] Priestman MA, Healy ML, Funke T, Becker A, Schonbrunn E. Molecular basis for the glyphosate-insensitivity of the reaction of 5-enolpyruvylshikimate 3-phosphate synthase with shikimate. FEBS Lett. 2005 Oct 24;579(25):5773-80. PMID:16225867 doi:10.1016/j.febslet.2005.09.066

[2] Funke T, Han H, Healy-Fried ML, Fischer M, Schonbrunn E. Molecular basis for the herbicide resistance of Roundup Ready crops. Proc Natl Acad Sci U S A. 2006 Aug 29;103(35):13010-5. Epub 2006 Aug 17. PMID:16916934

[3] Schonbrunn E, Eschenburg S, Shuttleworth WA, Schloss JV, Amrhein N, Evans JN, Kabsch W. Interaction of the herbicide glyphosate with its target enzyme 5-enolpyruvylshikimate 3-phosphate synthase in atomic detail. Proc Natl Acad Sci U S A. 2001 Feb 13;98(4):1376-80. PMID:11171958 doi:http://dx.doi.org/10.1073/pnas.98.4.1376

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