User:Ericksoe/sandbox

In enzymology, a 3-dehydroquinate synthase is an enzyme that catalyzes the chemical reaction


 * 3-deoxy-arabino-heptulosonate 7-phosphate $$\rightleftharpoons$$ 3-dehydroquinate + phosphate

Hence, this enzyme has one substrate, 3-deoxy-arabino-heptulosonate 7-phosphate, and two products, 3-dehydroquinate and phosphate. The protein uses NAD+ to catalyze the reaction. This reaction is part of the shikimate pathway which is involved in the biosynthesis of aromatic amino acids.

This enzyme belongs to the family of lyases, specifically those carbon-oxygen lyases acting on phosphates. This enzyme participates in phenylalanine, tyrosine and tryptophan biosynthesis. It employs one cofactor, cobalt.

Background
The shikimate pathway is composed of seven steps, each catalyzed by an enzyme. The shikimate pathway is responsible for producing the precursors for aromatic amino acids, 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 and 4-erythrose phosphate into chorismate, 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 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 which includes alcohol oxidation, phosphate b-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. In most bacteria, this enzyme has only one function. However, in some organisms, it forms a complex with other enzymes. This complex is known as the AROM complex. The AROM complex is a pentafunctional polypeptide, which contains enzymes that catalyze steps two, three, four, and five of the shikimate pathway. In addition, dehydroquinate synthase is of particular interest because of its complicated activity relative to its small size.

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, works by inhibiting another enzyme in the shikimate pathway. The shikimate pathway is an ideal choice for herbicides because this pathway does not exist in animals or people so people are not directly affected. Roundup uses an enzyme inhibitor, glyphosphate, 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, and without aromatic amino acids, plants cannot survive. However, Monsanto developed a bacterial form of EPSP synthase which was not inhibited by Roundup. Monsanto introduced this gene into plants using agrobacterium 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 of this enzyme class is 3-deoxy-arabino-heptulonate-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).