The
enzyme
Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...
3-dehydroquinate synthase (EC 4.2.3.4)
catalyzes the
chemical reaction
A chemical reaction is a process that leads to the IUPAC nomenclature for organic transformations, chemical transformation of one set of chemical substances to another. Classically, chemical reactions encompass changes that only involve the pos ...
:
D-''arabino''-hept-2-ulosonate 7-phosphate">3-deoxy-D-''arabino''-hept-2-ulosonate 7-phosphate 3-dehydroquinate + phosphate
The protein uses
NAD+ to catalyze the reaction.
This reaction is part of 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) ...
which is involved in the biosynthesis of aromatic amino acids.
3-Dehydroquinate synthase belongs to the family of
lyase
In biochemistry, a lyase is an enzyme that catalyzes the breaking (an elimination reaction) of various chemical bonds by means other than hydrolysis (a substitution reaction) and oxidation, often forming a new double bond or a new ring structure. ...
s, to be specific those carbon-oxygen lyases acting on phosphates. 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 aromatic ...
biosynthesis. It employs one
cofactor,
cobalt
Cobalt is a chemical element with the symbol Co and atomic number 27. As with nickel, cobalt is found in the Earth's crust only in a chemically combined form, save for small deposits found in alloys of natural meteoric iron. The free element, pr ...
(Co
2+).
Background
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) ...
is composed of seven steps, each catalyzed by an
enzyme
Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...
. The shikimate pathway is responsible for producing the precursors for
aromatic amino acids
An aromatic amino acid is an amino acid that includes an aromatic ring.
Among the 20 standard amino acids, the following are classically considered aromatic: phenylalanine, tryptophan and tyrosine. Although histidine contains an aromatic ring, ...
, which are essential to our diets because we cannot synthesize them in our bodies. Only plants, bacteria, and microbial eukaryotes are capable of producing aromatic amino acids. The pathway ultimately converts
phosphoenolpyruvate
Phosphoenolpyruvate (2-phosphoenolpyruvate, PEP) is the ester derived from the enol of pyruvate and phosphate. It exists as an anion. PEP is an important intermediate in biochemistry. It has the highest-energy phosphate bond found (−61.9 kJ/ ...
and 4-erythrose phosphate into
chorismate
Chorismic acid, more commonly known as its anionic form chorismate, is an important biochemical intermediate in plants and microorganisms. It is a precursor for:
* The aromatic amino acids phenylalanine, tryptophan, and tyrosine
* Indole, indole d ...
, the precursor to aromatic amino acids. 3-Dehydroquinate synthase is the enzyme that catalyzes reaction in the second step of this pathway. This second step of the reaction eliminates a phosphate from 3-deoxy-D-arabino-heptulosonate 7-phosphate, which results in 3-dehydroquinate. 3-Dehydroquinate synthase is a
monomeric
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
Mo ...
enzyme, and has a molecular weight of 39,000.
3-dehydroquinate synthase is activated by inorganic phosphate, and requires
NAD+ for activity, although the reaction in total is neutral when catalyzed by an enzyme.
Function
3-Dehydroquinate synthase utilizes a complex multi-step mechanism that includes alcohol oxidation, phosphate β-elimination, carbonyl reduction, ring opening, and intramolecular aldol condensation.
Dehydroquinate synthase requires
NAD+ and a cobalt
cofactor to catalyze the conversion of 3-deoxy-D-arabino-heptulosonate 7-phosphate into 3-dehydroquinate. Dehydroquinate synthase is of particular interest because of its complicated activity relative to its small size.
In most bacteria, this enzyme has only one function. However, in fungi and protists, it is part of the pentafunctional
AROM complex that comprises steps two, three, four, five and six of the shikimate pathway. Together with
3-dehydroquinate dehydratase, 3-dehydroquinate synthase forms the core of this complex.
Applications
3-Dehydroquinate synthase catalyzes the second step in the shikimate pathway, which is essential for the production of aromatic amino acids in bacteria, plants, and fungi, but not mammals. This makes it an ideal target for new antimicrobial agents, anti-parasitic agents, and herbicides.
Other enzymes in the shikimate pathway have already been targeted and put to use as herbicides. Roundup, a common herbicide made by
Monsanto
The Monsanto Company () was an American agrochemical and agricultural biotechnology corporation founded in 1901 and headquartered in Creve Coeur, Missouri. Monsanto's best known product is Roundup, a glyphosate-based herbicide, developed in th ...
, works by inhibiting another enzyme in 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) ...
. The shikimate pathway is an ideal choice for
herbicides
Herbicides (, ), also commonly known as weedkillers, are substances used to control undesired plants, also known as weeds.EPA. February 201Pesticides Industry. Sales and Usage 2006 and 2007: Market Estimates. Summary in press releasMain page fo ...
because this pathway does not exist in animals or people so people are not directly affected. Roundup uses an
enzyme inhibitor
An enzyme inhibitor is a molecule that binds to an enzyme and blocks its activity. Enzymes are proteins that speed up chemical reactions necessary for life, in which substrate molecules are converted into products. An enzyme facilitates a sp ...
,
glyphosate
Glyphosate (IUPAC name: ''N''-(phosphonomethyl)glycine) is a broad-spectrum Herbicide, systemic herbicide and Crop desiccation, crop desiccant. It is an organophosphorus compound, specifically a phosphonate, which acts by inhibiting the plan ...
, to block one of the steps of the shikimate pathway. Glyphosate inhibits 5-enolpyruvylshikimate-3-phosphate synthase (EPSP synthase), which ultimately blocks the production of
aromatic amino acids
An aromatic amino acid is an amino acid that includes an aromatic ring.
Among the 20 standard amino acids, the following are classically considered aromatic: phenylalanine, tryptophan and tyrosine. Although histidine contains an aromatic ring, ...
, and, without
aromatic amino acids
An aromatic amino acid is an amino acid that includes an aromatic ring.
Among the 20 standard amino acids, the following are classically considered aromatic: phenylalanine, tryptophan and tyrosine. Although histidine contains an aromatic ring, ...
, plants cannot survive. However,
Monsanto
The Monsanto Company () was an American agrochemical and agricultural biotechnology corporation founded in 1901 and headquartered in Creve Coeur, Missouri. Monsanto's best known product is Roundup, a glyphosate-based herbicide, developed in th ...
developed a bacterial form of EPSP synthase that was not inhibited by Roundup. Monsanto introduced this gene into plants using
agrobacterium
''Agrobacterium'' is a genus of Gram-negative bacteria established by H. J. Conn that uses horizontal gene transfer to cause tumors in plants. '' Agrobacterium tumefaciens'' is the most commonly studied species in this genus. ''Agrobacterium'' i ...
and the result was a plant that was resistant to Roundup. This meant that all plants without the bacterial gene would die, leading a much higher degree of weed control.
Nomenclature
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 3-deoxy-
D-''arabino''-hept-2-ulosonate-7-phosphate phosphate-lyase (cyclizing; 3-dehydroquinate-forming). Other names in common use include 5-dehydroquinate synthase, 5-dehydroquinic acid synthetase, dehydroquinate synthase, 3-dehydroquinate synthetase, 3-deoxy-arabino-heptulosonate-7-phosphate phosphate-lyase, (cyclizing), and 3-deoxy-arabino-heptulonate-7-phosphate phosphate-lyase (cyclizing).
References
Further reading
*
*
*
*
{{Portal bar, Biology, border=no
EC 4.2.3
Cobalt enzymes
Enzymes of known structure