| Function
5-enolpyruvylshikimate 3-phosphate (EPSP) synthase is a key enzyme for the biosynthesis of aromatic amino acids in plants and many microbes. Consequently. 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].
Relevance
EPSP synthase is a target for drugs and herbicides like Roundup.
Structural insights
The enzyme has two domains, with the active site found in the interdomain cleft (open conformation). There is a substantial structural change upon substrate binding, resulting in a closed conformation. See animation of this process. Glyphosate (also known as Roundup) occupies the binding site of the second substrate, phosphoenol pyruvate [2].
- ↑ 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
- ↑ 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:https://dx.doi.org/10.1073/pnas.98.4.1376
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3D structures of EPSP synthase
Updated on 20-October-2017
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- 5-enolpyruvylshikimate 3-phosphate (EPSP) synthase
- 1eps – EcEPSP – Escherichia coli
- 1p88, 1p89 - EcEPSP N terminal - NMR
- 1rf5 - SpEPSP – Streptococcus pneumoniae
- 2bjb, 2o15 – MtEPSP – Mycobacterium tuberculosis
- 2gg4 – AgEPSP – Agrobacterium
- 3roi, 3tr1, 4gfp – CbEPSP – Coxiella burnetii
- 3ti2 - VcEPSP N terminal – Vibrio cholerae
- 3rmt – EPSP – Bacillus halodurans
- EPSP synthase binary complex
- EPSP synthase ternary complex
- 1g6s - EcEPSP + S3P + glyphosate
- 2qft, 2qfu, 3fjz, 3fk1 - EcEPSP (mutant) + S3P + glyphosate
- 2aay - EcEPSP + shikimate + glyphosate
- 1rf6 - SpEPSP + S3P + glyphosate
- 2gga - AgEPSP + S3P + glyphosate
- 2ggd - AgEPSP (mutant) + S3P + glyphosate
- 2o0e - MtEPSP + S3P + phosphoenolpyruvate
- 3nvs - VcEPSP + S3P + glyphosate
- 3slh - CbEPSP + S3P + glyphosate
References
