The

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different molecule ...

chorismate synthase (EC 4.2.3.5)

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 break ...

:5-''O''-(1-carboxyvinyl)-3-phosphoshikimate

\rightleftharpoons

chorismate + phosphate This enzyme belongs to the family of

lyase In biochemistry, a lyase is an enzyme that catalyzes the breaking (an elimination reaction) of various chemical bond A chemical bond is a lasting attraction between atoms or ions that enables the formation of molecules and crystals. The bon ...

s, specifically those carbon-oxygen lyases acting on phosphates. The

systematic name A systematic name is a name given in a systematic way to one unique group, organism, object or chemical substance, out of a specific population or collection. Systematic names are usually part of a nomenclature. A semisystematic name or semitrivial ...

of this enzyme class is 5-''O''-(1-carboxyvinyl)-3-phosphoshikimate phosphate-lyase (chorismate-forming). This enzyme is also called 5-''O''-(1-carboxyvinyl)-3-phosphoshikimate phosphate-lyase. This enzyme participates in

phenylalanine Phenylalanine (symbol Phe or F) is an essential α-amino acid with the formula . It can be viewed as a benzyl group substituted for the methyl group of alanine, or a phenyl group in place of a terminal hydrogen of alanine. This essential amino a ...

tyrosine -Tyrosine or tyrosine (symbol Tyr or Y) or 4-hydroxyphenylalanine is one of the 20 standard amino acids that are used by cells to synthesize proteins. It is a non-essential amino acid with a polar side group. The word "tyrosine" is from the Gr ...

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 aromati ...

biosynthesis. Chorismate synthase catalyzes the last of the seven steps in the

shikimate Shikimic acid, more commonly known as its anionic form shikimate, is a cyclohexene, a cyclitol and a cyclohexanecarboxylic acid. It is an important biochemical metabolite in plants and microorganisms. Its name comes from the Japanese flower ''sh ...

pathway which is used in prokaryotes, fungi and plants for the biosynthesis of

aromatic amino acids An aromatic amino acid is an amino acid that includes an aromaticity, aromatic ring. Among the 20 standard amino acids, the following are classically considered aromatic: phenylalanine, tryptophan and tyrosine. Although histidine contains an ar ...

. It catalyzes the 1,4-trans elimination of the

phosphate group In chemistry, a phosphate is an anion, salt, functional group or ester derived from a phosphoric acid. It most commonly means orthophosphate, a derivative of orthophosphoric acid . The phosphate or orthophosphate ion is derived from phosph ...

from

5-enolpyruvylshikimate-3-phosphate 5-enolpyruvylshikimate-3-phosphate (EPSP) synthase is an enzyme produced by plants and microorganisms. EPSPS catalyzes the chemical reaction: : phosphoenolpyruvate (PEP) + 3-phospho shikimate (S3P) phosphate + 5-enolpyruvylshikimate-3-phospha ...

(EPSP) to form chorismate which can then be used in phenylalanine, tyrosine or tryptophan biosynthesis. Chorismate synthase requires the presence of a reduced

flavin mononucleotide Flavin mononucleotide (FMN), or riboflavin-5′-phosphate, is a biomolecule produced from riboflavin (vitamin B2) by the enzyme riboflavin kinase and functions as the prosthetic group of various oxidoreductases, including NADH dehydrogenase, a ...

(FMNH2 or FADH2) for its activity. Chorismate synthase from various sources shows a high degree of sequence conservation. It is a protein of about 360 to 400 amino-acid residues.

Biological and practical function

The shikimate pathway synthesises aromatic amino acids as well as other aromatic compounds that have various involvement with processes such as "UV protection, electron transport, signaling, communication, plant defense, and the wound response". Moreover, the enzymes catalysing the Shikimate pathway may be potentially useful in the development of new herbicides and antibiotics. This is due to the fact that the shikimate pathway is not present in humans. It is, therefore, an ideal target for herbicides because chemicals used to inhibit the shikimate pathway should not have an effect on humans. Also, the products created by the shikimate pathway are essential to plant life, so, if the function of the pathway is inhibited, this has a fatal effect on the plant. The enzymes in the shikimate pathway, and chorismate synthase specifically,are also considered to be potential targets for new

antimicrobial An antimicrobial is an agent that kills microorganisms or stops their growth. Antimicrobial medicines can be grouped according to the microorganisms they act primarily against. For example, antibiotics are used against bacteria, and antifungals ...

chemotherapy treatments for Mycobacterium tuberculosis. This is important since drugs resistant strains of M. tuberculosis continue to emerge. Studies have shown that the "shikimate pathway is essential for M. tuberculosis viability" making it an attractive target for new antimycobacterial agents.

Structural studies

As of late 2007, 9 structures have been solved for this class of enzymes, with PDB accession codes , , , , , , , , and . The crystal structure of chorismate synthase is a

homotetramer A tetrameric protein is a protein with a quaternary structure of four subunits (tetrameric). Homotetramers have four identical subunits (such as glutathione S-transferase), and heterotetramers are complexes of different subunits. A tetramer ca ...

with one FMN molecule non-covalently bound to each of the four

monomers In chemistry, a monomer ( ; ''mono-'', "one" + '' -mer'', "part") is a molecule that can react together with other monomer molecules to form a larger polymer chain or three-dimensional network in a process called polymerization. Classification ...

. Each monomer is made up of 9 alpha helices and 18 beta strands and the core is assembled in a unique beta-alpha-beta sandwich fold. The active sites for FMN-binding are made up of clusters of flexible loops and the area around these regions have highly positive electromagnetic potential. There are two

histidine Histidine (symbol His or H) is an essential amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated –NH3+ form under biological conditions), a carboxylic acid group (which is in the ...

residues located at the active site which are thought to protonate the reduced flavin molecule and the leaving phosphate group of the substrate.

Mechanism

Reduced flavin (FMN) transfers an electron to the substrate resulting in cleavage of the C--O bond. How this flavin is obtained differs from one organism to another and the process is not completely understood. Following the binding of EPSP, the flavin reaction intermediate is formed, but this process is completed prior to EPSP consumption. After EPSP has been converted to chorismate, and after the phosphate has been released from the enzyme,then the flavin intermediate will decay. The chorismate synthase enzyme can be divided into two categories based on how reduced FMN is obtained.

Bifunctional In organic chemistry, when a single organic molecule has two different functional groups, it is called a bifunctional molecule . A bifunctional molecule has the properties of two different types of functional groups, such as an alcohol (), amide ( ...

chorismate synthase is present in fungi and require a "second enzymatic activity, an NAD(P)H-dependent flavin reductase"." Monofunctional chorismate synthase is found in plants and E.coli and is only active in an anaerobic environment with "chemically or enzymatically reduced flavin". There is no net

redox Redox (reduction–oxidation, , ) is a type of chemical reaction in which the oxidation states of substrate (chemistry), substrate change. Oxidation is the loss of Electron, electrons or an increase in the oxidation state, while reduction ...

change in the reaction. The flavin molecule is not consumed during the reaction and merely acts as a

catalyst 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 ...

References

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External links

* {{Portal bar, Biology, border=no EC 4.2.3 Enzymes of known structure