EPSP synthase: Difference between revisions

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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-== Structure of EPSP Synthase ==
+<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'>
-<StructureSection load='1eps' size='350' side='right' caption='Structure of EPSP synthase (PDB entry [[1eps]])' scene=''>
--enolpyruvylshikimate 3-phosphate (EPSP) synthase is a key enzyme for the biosynthesis of aromatic amino acids in plants and many microbes.  Consequently, it is a target for drugs and herbicides. EPSP synthase catalyzes the addition of phosphoenol pyruvate (PEP) to shikimate-3-phosphate, generating 5-enolpyruvylshikimate-3-phosphate, which is a precursor for phenylalanine and tyrosine.
+__TOC__
+== Function ==
-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 closed formation.  Glyphosate (also known as Roundup) occupies the binding site of the second substrate, phosphoenol pyruvate.
+'''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>,
+== Structural insights ==
+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.
+==3D structures of EPSP synthase ==
-</StructureSection>
+[[EPSP synthase 3D structures]]
-==References==
+</StructureSection>
-</ref>
+== References ==
+<references/>
+[[Category:Topic Page]]