EPSP synthase

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EPSP Synthase (3-phosphoshikimate 1-carboxyvinyltransferase)
EPSP synthase.PNG
EPSP synthase liganded with shikimate.[1]
Identifiers
EC number 2.5.1.19
CAS number 9068-73-9
Databases
IntEnz IntEnz view
BRENDA BRENDA entry
ExPASy NiceZyme view
KEGG KEGG entry
MetaCyc metabolic pathway
PRIAM profile
PDB structures RCSB PDB PDBe PDBsum
Gene Ontology AmiGO / EGO
EPSP synthase (3-phosphoshikimate 1-carboxyvinyltransferase)
EPSP synthase cartoon.PNG
Ribbon diagram of EPSP synthase
Identifiers
Symbol EPSP_synthase
Pfam PF00275
InterPro IPR001986
PROSITE PDOC00097
SCOP 1eps
SUPERFAMILY 1eps

5-enolpyruvylshikimate-3-phosphate (EPSP) synthase is an enzyme that catalyzes the chemical reaction:

phosphoenolpyruvate + 3-phosphoshikimate \rightleftharpoons phosphate + 5-enolpyruvylshikimate-3-phosphate (EPSP)

Thus, the two substrates of this enzyme are phosphoenolpyruvate and 3-phospho-shikimate, whereas its two products are phosphate and 5-enolpyruvylshikimate-3-phosphate.

It is the biological target of the herbicide, glyphosate and a glyphosate-resistant version of this gene has been used in genetically modified crops.

Nomenclature[edit]

The enzyme belongs to the family of transferases, to be specific those transferring aryl or alkyl groups other than methyl groups. The systematic name of this enzyme class is phosphoenolpyruvate:3-phosphoshikimate 5-O-(1-carboxyvinyl)-transferase. Other names in common use include:

  • 5-enolpyruvylshikimate-3-phosphate synthase,
  • 3-enolpyruvylshikimate 5-phosphate synthase,
  • 3-enolpyruvylshikimic acid-5-phosphate synthetase,
  • 5'-enolpyruvylshikimate-3-phosphate synthase,
  • 5-enolpyruvyl-3-phosphoshikimate synthase,
  • 5-enolpyruvylshikimate-3-phosphate synthetase,
  • 5-enolpyruvylshikimate-3-phosphoric acid synthase,
  • enolpyruvylshikimate phosphate synthase, and
  • 3-phosphoshikimate 1-carboxyvinyl transferase.

Structure[edit]

EPSP synthase is a monomeric enzyme with a molecular mass of about 46,000.[2][3][4] It is composed of two domains, which are joined by protein strands. This strand acts as a hinge, and can bring the two protein domains closer together. When a substrate binds to the enzyme, ligand bonding causes the two parts of the enzyme to clamp down around the substrate in the active site.

EPSP synthase has been divided into two groups according to glyphosate sensitivity. Class I enzyme, contained in plants and in some bacteria, is inhibited at low micromolar glyphosate concentrations, whereas class II enzyme, found in other bacteria, is resistant to inhibition by glyphosate.[5]

Shikimate pathway[edit]

EPSP synthase participates in the biosynthesis of the aromatic amino acids phenylalanine, tyrosine and tryptophan via the shikimate pathway in bacteria, fungi, and plants. EPSP synthase is produced only by plants and micro-organisms; the gene coding for it is not in the mammalian genome.[6][7] Gut flora of some animals contain EPSPS.[8]

Reaction[edit]

EPSP synthase catalyzes the reaction which converts shikimate-3-phosphate plus phosphoenolpyruvate to 5-enolpyruvylshikimate-3-phosphate (EPSP).

EPSPreactionII.tif

Herbicide target[edit]

ESPS synthase is the biological target for the herbicide, glyphosate. Glyphosate is a competitive inhibitor of PEP, acting as a transition state analog that binds more tightly to the EPSPS-S3P complex than PEP and inhibits the shikimate pathway. This binding leads to inhibition of the enzyme's catalysis and shuts down the pathway. Eventually this results in organism death from lack of aromatic amino acids the organism requires to survive.[9][5]

A version of the enzyme that both was resistant to glyphosate and that was still efficient enough to drive adequate plant growth was identified by Monsanto scientists after much trial and error in an Agrobacterium strain called CP4, which was found surviving in a waste-fed column at a glyphosate production facility; this version of enzyme, CP4 EPSPS, is the one that has been engineered into several genetically modified crops.[5][10]

References[edit]

  1. ^ Priestman MA, Healy ML, Funke T, Becker A, Schönbrunn E (October 2005). "Molecular basis for the glyphosate-insensitivity of the reaction of 5-enolpyruvylshikimate 3-phosphate synthase with shikimate". FEBS Lett. 579 (25): 5773–80. doi:10.1016/j.febslet.2005.09.066. PMID 16225867. 
  2. ^ Goldsbrough, Peter (1990). "Goldsbrough, Peter B., et al. "Gene amplification in glyphosate tolerant tobacco cells." Plant science 72.1 (1990): 53-62.". Plant Science. 72 (1): 53–62. 
  3. ^ Abdel-Meguid SS, Smith WW, Bild GS (Dec 1985). "Crystallization of 5-enolpyruvylshikimate 3-phosphate synthase from Escherichia coli". Journal of Molecular Biology 186 (3): 673. PMID 3912512. 
  4. ^ Ream JE, Steinrücken HC, Porter CA, Sikorski JA (May 1988). "Purification and Properties of 5-Enolpyruvylshikimate-3-Phosphate Synthase from Dark-Grown Seedlings of Sorghum bicolor". Plant Physiology 87 (1): 232–8. PMC 1054731. PMID 16666109. 
  5. ^ a b c Pollegioni L, Schonbrunn E, Siehl D (Aug 2011). "Molecular basis of glyphosate resistance-different approaches through protein engineering". The FEBS Journal 278 (16): 2753–66. doi:10.1111/j.1742-4658.2011.08214.x. PMID 21668647. 
  6. ^ Funke T, Han H, Healy-Fried ML, Fischer M, Schönbrunn E (Aug 2006). "Molecular basis for the herbicide resistance of Roundup Ready crops". Proceedings of the National Academy of Sciences of the United States of America 103 (35): 13010–5. Bibcode:2006PNAS..10313010. doi:10.1073/pnas.0603638103. JSTOR 30050705. PMC 1559744. PMID 16916934. 
  7. ^ Maeda H, Dudareva N (2012). "The shikimate pathway and aromatic amino Acid biosynthesis in plants". Annual Review of Plant Biology 63 (1): 73–105. doi:10.1146/annurev-arplant-042811-105439. PMID 22554242. The AAA pathways consist of the shikimate pathway (the prechorismate pathway) and individual postchorismate pathways leading to Trp, Phe, and Tyr.... These pathways are found in bacteria, fungi, plants, and some protists but are absent in animals. Therefore, AAAs and some of their derivatives (vitamins) are essential nutrients in the human diet, although in animals Tyr can be synthesized from Phe by Phe hydroxylase....The absence of the AAA pathways in animals also makes these pathways attractive targets for antimicrobial agents and herbicides. 
  8. ^ Cerdeira AL, Duke SO (2006). "The current status and environmental impacts of glyphosate-resistant crops: a review". Journal of Environmental Quality 35 (5): 1633–58. doi:10.2134/jeq2005.0378. PMID 16899736. 
  9. ^ Schönbrunn E, Eschenburg S, Shuttleworth WA, Schloss JV, Amrhein N, Evans JN, Kabsch W (Feb 2001). "Interaction of the herbicide glyphosate with its target enzyme 5-enolpyruvylshikimate 3-phosphate synthase in atomic detail". Proceedings of the National Academy of Sciences of the United States of America 98 (4): 1376–80. doi:10.1073/pnas.98.4.1376. PMC 29264. PMID 11171958. 
  10. ^ Green JM, Owen MD (Jun 2011). "Herbicide-resistant crops: utilities and limitations for herbicide-resistant weed management". Journal of Agricultural and Food Chemistry 59 (11): 5819–29. doi:10.1021/jf101286h. PMID 20586458. 

Further reading[edit]