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242  structures 8103  species 0  interactions 19761  sequences 106  architectures

Family: EPSP_synthase (PF00275)

Summary: EPSP synthase (3-phosphoshikimate 1-carboxyvinyltransferase)

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EPSP synthase Edit Wikipedia article

EPSP Synthase (3-phosphoshikimate 1-carboxyvinyltransferase)
EPSP synthase.PNG
EPSP synthase liganded with shikimate.[1]
EC number2.5.1.19
CAS number9068-73-9
IntEnzIntEnz view
ExPASyNiceZyme view
MetaCycmetabolic pathway
PDB structuresRCSB PDB PDBe PDBsum
Gene OntologyAmiGO / QuickGO
EPSP synthase (3-phosphoshikimate 1-carboxyvinyltransferase)
EPSP synthase cartoon.PNG
Ribbon diagram of EPSP synthase

5-enolpyruvylshikimate-3-phosphate (EPSP) synthase is an enzyme produced by plants and microorganisms. EPSPS catalyzes the chemical reaction:

phosphoenolpyruvate (PEP) + 3-phosphoshikimate (S3P) ⇌ phosphate + 5-enolpyruvylshikimate-3-phosphate (EPSP)

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

This enzyme is not present in animals, so it presents an attractive biological target for herbicides, such as glyphosate. A glyphosate-resistant version of this gene has been used in genetically modified crops.


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.


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

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]


EPSP synthase catalyzes the reaction which converts shikimate-3-phosphate plus phosphoenolpyruvate to 5-enolpyruvylshikimate-3-phosphate (EPSP) by way of an acetal-like tetrahedral intermediate.[9][10] Basic and amino acids in the active site are involved in deprotonation of the hydroxyl group of PEP and in the proton-exchange steps related to the tetrahedral intermediate itself, respectively.[11]


Studies of the enzyme kinetics for this reaction have determined the specific sequence and energetics of each step of the process.[12]

Herbicide target

EPSP 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.[5][13]

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][14]


  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). "Gene amplification in glyphosate tolerant tobacco cells". Plant Science. 72 (1): 53–62. doi:10.1016/0168-9452(90)90186-r.
  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. doi:10.1016/0022-2836(85)90140-8. 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. doi:10.1104/pp.87.1.232. 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. PMC 3145815. 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..10313010F. 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. ^ " EPSP synthase: A tetrahedral ketal phosphate enzyme intermediate". Comprehensive Natural Products II. Chemistry and Biology. Reference Module in Chemistry, Molecular Sciences and Chemical Engineering. 8. 2010. pp. 663–688.
  10. ^ Anderson, Karen S.; Sammons, R. Douglas; Leo, Gregory C.; Sikorski, James A.; Benesi, Alan J.; Johnson, Kenneth A. (1990). "Observation by carbon-13 NMR of the EPSP synthase tetrahedral intermediate bound to the enzyme active site". Biochemistry. 29 (6): 1460–1465. doi:10.1021/bi00458a017. PMID 2334707.
  11. ^ Park, HaJeung; Hilsenbeck, Jacqueline L.; Kim, Hak Jun; Shuttleworth, Wendy A.; Park, Yong Ho; Evans, Jeremy N.; Kang, ChulHee (2004). "Structural studies of Streptococcus pneumoniae EPSP synthase in unliganded state, tetrahedral intermediate‐bound state and S3P‐GLP‐bound state". Molecular Microbiology. 51 (4): 963–971. doi:10.1046/j.1365-2958.2003.03885.x.
  12. ^ Anderson, Karen S.; Sikorski, James A.; Johnson, Kenneth A. (1988). "A tetrahedral intermediate in the EPSP synthase reaction observed by rapid quench kinetics". Biochemistry. 27 (19): 7395–7406. doi:10.1021/bi00419a034.
  13. ^ 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. Bibcode:2001PNAS...98.1376S. doi:10.1073/pnas.98.4.1376. PMC 29264. PMID 11171958.
  14. ^ 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. PMC 3105486. PMID 20586458.

Further reading

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EPSP synthase (3-phosphoshikimate 1-carboxyvinyltransferase) Provide feedback

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This tab holds annotation information from the InterPro database.

InterPro entry IPR001986

This entry represents the core domain of 3-phosphoshikimate 1-carboxyvinyltransferase and UDP-N-acetylglucosamine 1-carboxyvinyltransferase. It transfers enolpryruvate from phosphoenolpyruvate to 3-phosphoshikimate and UDP-N-acetyl-alpha-D-glucosamine respectively.

Gene Ontology

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Pfam Clan

This family is a member of clan EPT_RTPC (CL0290), which has the following description:

This superfamily includes Enolpyruvate transferase (EPT) and RNA 3'-terminal phosphate cyclase (RTPC).

The clan contains the following 2 members:

EPSP_synthase RTC


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Seed source: Prosite
Previous IDs: EPSP_syntase;
Type: Family
Sequence Ontology: SO:0100021
Author: Finn RD
Number in seed: 19
Number in full: 19761
Average length of the domain: 392.60 aa
Average identity of full alignment: 25 %
Average coverage of the sequence by the domain: 82.89 %

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HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 57096847 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 22.8 22.8
Trusted cut-off 23.0 22.9
Noise cut-off 22.7 22.7
Model length: 416
Family (HMM) version: 22
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For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the EPSP_synthase domain has been found. There are 242 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.

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