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<StructureSection load='1eps' size='350' side='right' caption='Structure of EPSP synthase (PDB entry [[1eps]])' scene=''>
<StructureSection load='' size='350' side='right' caption='Structure of E. coli EPSP synthase complex with shikimate-3-phosphate, the herbicide glyphosate and formic acid (PDB entry [[1g6s]])' scene='57/570585/Cv/1'>
 
__TOC__
== Function ==
== 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<ref>PMID:16225867</ref>.  
'''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<ref>PMID:16225867</ref>. 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. <ref>PMID:16916934</ref>,


== Relevance ==
== Structural insights ==


EPSP synthase is a target for drugs and herbicides.
The enzyme has two domains, with the active site found in the interdomain cleft <scene name='57/570585/Two_domains/5'>(open conformation)</scene>.  There is a substantial structural change upon substrate binding, resulting in a <scene name='57/570585/Closed_formation/3'>closed</scene> conformation. <scene name='57/570585/Cv/9'>See animation of this process</scene>. '''Glyphosate''' (also known as '''Roundup''') occupies the <scene name='57/570585/Glyphosate_s3p/1'>binding site</scene> 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 accommodate 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.


== Structural insights ==
==3D structures of EPSP synthase ==


The enzyme has <scene name='57/570585/Two_domains/1'>two domains</scene>, with the active site found in the interdomain cleft.  There is a substantial structural change upon substrate binding, resulting in a <scene name='57/570585/Closed_formation/1'>closed formation</scene>.  '''Glyphosate''' (also known as '''Roundup''') occupies the binding site of the second substrate, phosphoenol pyruvate. 
[[EPSP synthase 3D structures]]
</StructureSection>
</StructureSection>


===3D structures of EPSP synthase ===
Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
{{#tree:id=OrganizedByTopic|openlevels=0|
*5-enolpyruvylshikimate 3-phosphate (EPSP) synthase
**[[1eps]] – EcEPSP – ''Escherichia coli''<br />
**[[1p88]], [[1p89]] - EcEPSP N terminal - NMR<br />
**[[1rf5]] - SpEPSP – ''Streptococcus pneumoniae''<br />
**[[2bjb]], [[2o15]] – MtEPSP – ''Mycobacterium tuberculosis''<br />
**[[2gg4]] – AgEPSP – ''Agrobacterium''<br />
**[[3roi]], [[3tr1]], [[4gfp]] – CbEPSP – ''Coxiella burnetii''<br />
**[[3ti2]] - VcEPSP N terminal – ''Vibrio cholerae''<br />
**[[3rmt]] – EPSP – ''Bacillus halodurans''<br />
*EPSP synthase binary complex
**[[1g6t]] - EcEPSP + S3P <br />
**[[1mi4]], [[2qfq]], [[2qfs]], [[3fjx]], [[3fk0]] - EcEPSP (mutant) + S3P <br />
**[[1q36]] - EcEPSP (mutant) + S3P derivative<br />
**[[1x8r]], [[1x8t]] - EcEPSP + intermediate <br />
**[[2aa9]] – EcEPSP + shikimate<br />
**[[2pq9]] - EcEPSP + intermediate <br />
**[[1rf4]] - SpEPSP + intermediate <br />
**[[2o0b]], [[2o0d]] - MtEPSP + S3P <br />
**[[2gg6]] - AgEPSP + S3P <br />
**[[2pqb]], [[2pqc]], [[2pqd]] - AgEPSP + intermediate <br />
**[[2o0x]] - MtEPSP + intermediate <br />
**[[2o0z]] - MtEPSP + EPS <br />
**[[4egr]] - CbEPSP + phosphoenolpyruvate<br />
*EPSP synthase ternary complex
**[[1g6s]] - EcEPSP + S3P + glyphosate<br />
**[[2qft]], [[2qfu]], [[3fjz]], [[3fk1]] - EcEPSP (mutant) + S3P + glyphosate<br />
**[[2aay]] - EcEPSP + shikimate + glyphosate<br />
**[[1rf6]] - SpEPSP + S3P + glyphosate<br />
**[[2gga]] - AgEPSP + S3P + glyphosate<br />
**[[2ggd]] - AgEPSP (mutant) + S3P + glyphosate<br />
**[[2o0e]] - MtEPSP + S3P + phosphoenolpyruvate<br />
**[[3nvs]] - VcEPSP + S3P + glyphosate <br />
**[[3slh]] - CbEPSP + S3P + glyphosate<br />
}}
== References ==
== References ==
<references/>
<references/>


[[Category:Topic Page]]
[[Category:Topic Page]]

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

Ann Taylor, Michal Harel, Alexander Berchansky, Joel L. Sussman
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