5-enolpyruvylshikimate-3-phosphate (EPSP) synthase is an
enzyme produced by plants and
microorganisms. EPSPS
catalyzes
Catalysis () is the process of increasing the rate of a chemical reaction by adding a substance known as a catalyst (). Catalysts are not consumed in the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recyc ...
the
chemical reaction
A chemical reaction is a process that leads to the chemical transformation of one set of chemical substances to another. Classically, chemical reactions encompass changes that only involve the positions of electrons in the forming and breakin ...
:
:
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 animals. It presents an attractive
biological target
A biological target is anything within a living organism to which some other entity (like an endogenous ligand or a drug) is directed and/or binds, resulting in a change in its behavior or function. Examples of common classes of biological targets ...
for
herbicides, such as
glyphosate. A glyphosate-resistant version of this gene has been used in
genetically modified crops.
Nomenclature
The enzyme belongs to the family of
transferases, to be specific those transferring
aryl
In organic chemistry, an aryl is any functional group or substituent derived from an aromatic ring, usually an aromatic hydrocarbon, such as phenyl and naphthyl. "Aryl" is used for the sake of abbreviation or generalization, and "Ar" is used as ...
or
alkyl
In organic chemistry, an alkyl group is an alkane missing one hydrogen.
The term ''alkyl'' is intentionally unspecific to include many possible substitutions.
An acyclic alkyl has the general formula of . A cycloalkyl is derived from a cycloal ...
groups other than
methyl
In organic chemistry, a methyl group is an alkyl derived from methane, containing one carbon atom bonded to three hydrogen atoms, having chemical formula . In formulas, the group is often abbreviated as Me. This hydrocarbon group occurs in man ...
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
EPSP synthase is a monomeric enzyme with a molecular mass of about 46,000. 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.
Shikimate pathway
EPSP synthase participates in the biosynthesis of the
aromatic
In chemistry, aromaticity is a chemical property of cyclic ( ring-shaped), ''typically'' planar (flat) molecular structures with pi bonds in resonance (those containing delocalized electrons) that gives increased stability compared to satu ...
amino acids
phenylalanine,
tyrosine, and
tryptophan
Tryptophan (symbol Trp or W)
is an α-amino acid that is used in the biosynthesis of proteins. Tryptophan contains an α-amino group, an α-carboxylic acid group, and a side chain indole, making it a polar molecule with a non-polar aromatic ...
via the
shikimate pathway
The shikimate pathway (shikimic acid pathway) is a seven-step metabolic pathway used by bacteria, archaea, fungi, algae, some protozoans, and plants for the biosynthesis of folates and aromatic amino acids (tryptophan, phenylalanine, and tyrosine) ...
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.
Gut flora
Gut microbiota, gut microbiome, or gut flora, are the microorganisms, including bacteria, archaea, fungi, and viruses that live in the digestive tracts of animals. The gastrointestinal metagenome is the aggregate of all the genomes of the gut m ...
of some animals contain EPSPS.
Reaction
EPSP synthase catalyzes the reaction which converts shikimate-3-phosphate plus phosphoenolpyruvate to 5-enolpyruvylshikimate-3-phosphate (EPSP) by way of an
acetal
In organic chemistry, an acetal is a functional group with the connectivity . Here, the R groups can be organic fragments (a carbon atom, with arbitrary other atoms attached to that) or hydrogen, while the R' groups must be organic fragments n ...
-like
tetrahedral intermediate. Basic and
amino acid
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...
s in the
active site
In biology and biochemistry, the active site is the region of an enzyme where substrate molecules bind and undergo a chemical reaction. The active site consists of amino acid residues that form temporary bonds with the substrate (binding site) ...
are involved in
deprotonation of the
hydroxyl group of PEP and in the proton-exchange steps related to the tetrahedral intermediate itself, respectively.
Studies of the
enzyme kinetics
Enzyme kinetics is the study of the rates of enzyme-catalysed chemical reactions. In enzyme kinetics, the reaction rate is measured and the effects of varying the conditions of the reaction are investigated. Studying an enzyme's kinetics in th ...
for this reaction have determined the specific sequence and energetics of each step of the process.
Herbicide target
EPSP synthase is the biological target for the herbicide glyphosate.
Glyphosate is a
competitive inhibitor
Competitive inhibition is interruption of a chemical pathway owing to one chemical substance inhibiting the effect of another by competing with it for binding or bonding. Any metabolic or chemical messenger system can potentially be affected ...
of EPSP synthase, acting as a
transition state analog Transition state analogs (transition state analogues), are chemical compounds with a chemical structure that resembles the transition state of a substrate molecule in an enzyme-catalyzed chemical reaction. Enzymes interact with a substrate by m ...
that binds more tightly to the EPSPS-S3P complex than PEP and inhibits the
shikimate pathway
The shikimate pathway (shikimic acid pathway) is a seven-step metabolic pathway used by bacteria, archaea, fungi, algae, some protozoans, and plants for the biosynthesis of folates and aromatic amino acids (tryptophan, phenylalanine, and tyrosine) ...
. 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.
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 (). 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.
References
Further reading
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EC 2.5.1
Enzymes of known structure