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EPSP synthase

January 01, 1970

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

EPSP Synthase (3-phosphoshikimate 1-carboxyvinyltransferase)
EPSP synthase liganded with shikimate.[1]
Identifiers
EC no.2.5.1.19
CAS no.9068-73-9
Databases
IntEnzIntEnz view
BRENDABRENDA entry
ExPASyNiceZyme view
KEGGKEGG entry
MetaCycmetabolic pathway
PRIAMprofile
PDB structuresRCSB PDB PDBe PDBsum
Gene OntologyAmiGO / QuickGO
Search
PMCarticles
PubMedarticles
NCBIproteins
EPSP synthase (3-phosphoshikimate 1-carboxyvinyltransferase)
Ribbon diagram of EPSP synthase
Identifiers
SymbolEPSP_synthase
PfamPF00275
InterProIPR001986
PROSITEPDOC00097
SCOP21eps / SCOPe / SUPFAM
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary
phosphoenolpyruvate (PEP) + 3-phospho shikimate (S3P) ⇌ phosphate + 5-enolpyruvylshikimate-3-phosphate (EPSP)

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

This enzyme is not present in the genomes of animals. 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.

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) 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] A deprotonated lysine22 acts as a general base, deprotonating the hydroxyl of S3P such that the resulting oxyanion can attack the most electrophilic carbon of PEP. Glutamate341 acts as a general acid by donating a H+. The deprotonated glutamate341 then acts as a base, taking back its proton, and the S3P group is kicked off and protonated by the protonated lysine.

Herbicide target edit

EPSP synthase is the biological target for the herbicide glyphosate.[13] Glyphosate is a competitive inhibitor of EPSP synthase, 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][14]

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 (Q9R4E4). The strain CP4 was found surviving in a waste-fed column at a glyphosate production facility. The CP4 EPSP synthase enzyme has been engineered into several genetically modified crops.[5][15]

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. S2CID 26614581.
  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. ^ "8.18.4.1.1. EPSP synthase: A tetrahedral ketal phosphate enzyme intermediate". Comprehensive Natural Products II. Chemistry and Biology. Reference Module in Chemistry, Molecular Sciences and Chemical Engineering. Vol. 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. PMID 14763973. S2CID 45549442.
  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. PMID 3061457.
  13. ^ Fonseca, Emily C. M.; da Costa, Kauê S.; Lameira, Jerônimo; Alves, Cláudio Nahum; Lima, Anderson H. (2020). "Investigation of the target-site resistance of EPSP synthase mutants P106T and T102I/P106S against glyphosate". RSC Advances. 10 (72): 44352–44360. doi:10.1039/D0RA09061A. ISSN 2046-2069. PMC 9058485.
  14. ^ 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.
  15. ^ 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 edit

  • Morell H, Clark MJ, Knowles PF, Sprinson DB (Jan 1967). "The enzymic synthesis of chorismic and prephenic acids from 3-enolpyruvylshikimic acid 5-phosphate". The Journal of Biological Chemistry. 242 (1): 82–90. doi:10.1016/S0021-9258(18)96321-0. PMID 4289188.

January 01, 1970
epsp, synthase, enolpyruvylshikimate, phosphate, epsp, synthase, enzyme, produced, plants, microorganisms, epsps, catalyzes, chemical, reaction, epsp, synthase, phosphoshikimate, carboxyvinyltransferase, liganded, with, shikimate, identifiersec, 19cas, 9068, 9. 5 enolpyruvylshikimate 3 phosphate EPSP synthase is an enzyme produced by plants and microorganisms EPSPS catalyzes the chemical reaction EPSP Synthase 3 phosphoshikimate 1 carboxyvinyltransferase EPSP synthase liganded with shikimate 1 IdentifiersEC no 2 5 1 19CAS no 9068 73 9DatabasesIntEnzIntEnz viewBRENDABRENDA entryExPASyNiceZyme viewKEGGKEGG entryMetaCycmetabolic pathwayPRIAMprofilePDB structuresRCSB PDB PDBe PDBsumGene OntologyAmiGO QuickGOSearchPMCarticlesPubMedarticlesNCBIproteins EPSP synthase 3 phosphoshikimate 1 carboxyvinyltransferase Ribbon diagram of EPSP synthaseIdentifiersSymbolEPSP synthasePfamPF00275InterProIPR001986PROSITEPDOC00097SCOP21eps SCOPe SUPFAMAvailable protein structures Pfam structures ECOD PDBRCSB PDB PDBe PDBjPDBsumstructure summary phosphoenolpyruvate PEP 3 phospho shikimate S3P phosphate 5 enolpyruvylshikimate 3 phosphate EPSP Thus the two substrates of this enzyme are phosphoenolpyruvate PEP and 3 phosphoshikimate whereas its two products are phosphate and 5 enolpyruvylshikimate 3 phosphate This enzyme is not present in the genomes of animals 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 Contents 1 Nomenclature 2 Structure 3 Shikimate pathway 3 1 Reaction 4 Herbicide target 5 References 6 Further readingNomenclature editThe 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 editEPSP 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 editEPSP 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 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 nbsp Studies of the enzyme kinetics for this reaction have determined the specific sequence and energetics of each step of the process 12 A deprotonated lysine22 acts as a general base deprotonating the hydroxyl of S3P such that the resulting oxyanion can attack the most electrophilic carbon of PEP Glutamate341 acts as a general acid by donating a H The deprotonated glutamate341 then acts as a base taking back its proton and the S3P group is kicked off and protonated by the protonated lysine Herbicide target editEPSP synthase is the biological target for the herbicide glyphosate 13 Glyphosate is a competitive inhibitor of EPSP synthase 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 14 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 Q9R4E4 The strain CP4 was found surviving in a waste fed column at a glyphosate production facility The CP4 EPSP synthase enzyme has been engineered into several genetically modified crops 5 15 References edit Priestman MA Healy ML Funke T Becker A Schonbrunn 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 S2CID 26614581 Goldsbrough Peter 1990 Gene amplification in glyphosate tolerant tobacco cells Plant Science 72 1 53 62 doi 10 1016 0168 9452 90 90186 r 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 Ream JE Steinrucken 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 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 Funke T Han H Healy Fried ML Fischer M Schonbrunn 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 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 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 8 18 4 1 1 EPSP synthase A tetrahedral ketal phosphate enzyme intermediate Comprehensive Natural Products II Chemistry and Biology Reference Module in Chemistry Molecular Sciences and Chemical Engineering Vol 8 2010 pp 663 688 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 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 PMID 14763973 S2CID 45549442 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 PMID 3061457 Fonseca Emily C M da Costa Kaue S Lameira Jeronimo Alves Claudio Nahum Lima Anderson H 2020 Investigation of the target site resistance of EPSP synthase mutants P106T and T102I P106S against glyphosate RSC Advances 10 72 44352 44360 doi 10 1039 D0RA09061A ISSN 2046 2069 PMC 9058485 Schonbrunn 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 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 editMorell H Clark MJ Knowles PF Sprinson DB Jan 1967 The enzymic synthesis of chorismic and prephenic acids from 3 enolpyruvylshikimic acid 5 phosphate The Journal of Biological Chemistry 242 1 82 90 doi 10 1016 S0021 9258 18 96321 0 PMID 4289188 Portal nbsp Biology Retrieved from https en wikipedia org w index php title EPSP synthase amp oldid 1201727831 Herbicide target, wikipedia, wiki, book, books, library,

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