EPSP synthase

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== Structural insights ==
== Structural insights ==
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The enzyme has two domains, with the active site found in the interdomain cleft <scene name='57/570585/Two_domains/2'>(open conformation)</scene>. There is a substantial structural change upon substrate binding, resulting in a <scene name='57/570585/Closed_formation/2'>closed</scene> conformation. <scene name='57/570585/Cv/3'>See animation of this process</scene>. '''Glyphosate''' (also known as '''Roundup''') occupies the of the second substrate, phosphoenol pyruvate <ref>PMID:11171958</ref>. Interestingly CP4 EPSP synthase still binds glyphosate in the absence of PEP, but a conformational change in glyphosate to accomodate a steric clash with <scene name='57/570585/Glyphosate_s3p_distance/2'>Glu 354</scene> changes the IC50 by a factor of over 4,000, from 2.5 micromolar to 11 millimolar.
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The enzyme has two domains, with the active site found in the interdomain cleft <scene name='57/570585/Two_domains/2'>(open conformation)</scene>. There is a substantial structural change upon substrate binding, resulting in a <scene name='57/570585/Closed_formation/2'>closed</scene> conformation. <scene name='57/570585/Cv/3'>See animation of this process</scene>. '''Glyphosate''' (also known as '''Roundup''') occupies the of the second substrate, phosphoenol pyruvate <ref>PMID:11171958</ref>. Interestingly CP4 EPSP synthase still binds glyphosate in the absence of PEP, but a conformational change in glyphosate to accomodate a steric clash with <scene name='57/570585/Glyphosate_s3p_distance/2'>Glu 354</scene> 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.
</StructureSection>
</StructureSection>

Revision as of 15:18, 14 August 2018

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

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3D structures of EPSP synthase

Updated on 14-August-2018

References

  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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