3-dehydroquinate synthase

{{infobox enzyme

| Name = 3-dehydroquinate synthase

| EC_number = 4.2.3.4

| CAS_number = 37211-77-1

| GO_code = 0003856

| image = 3-dehydroquinate synthase 3CLH.png

| width =

| caption = Ribbon representation of the Helicobacter pylori 3-dehydroquinate synthase.{{PDB|3CLH}}; {{cite journal | vauthors = Liu JS, Cheng WC, Wang HJ, Chen YC, Wang WC | title = Structure-based inhibitor discovery of Helicobacter pylori dehydroquinate synthase | journal = Biochemical and Biophysical Research Communications | volume = 373 | issue = 1 | pages = 1–7 | date = August 2008 | pmid = 18503755 | doi = 10.1016/j.bbrc.2008.05.070 }}; rendered with [http://www.pymol.org MacPyMOL]

}}

{{Pfam_box

| Symbol = DHQ_synthase

| Name = 3-dehydroquinate synthase

| image = 1nrx.jpg

| width = 270

| caption = 3-Dehydroquinate synthase homodimer, Aspergillus nidulans

| Pfam= PF01761

| InterPro= IPR002658

| SMART=

| Prosite =

| SCOP = 1dqs

| TCDB =

| OPM family=

| OPM protein=

| PDB=

}}

The enzyme 3-dehydroquinate synthase (EC 4.2.3.4) catalyzes the chemical reaction

:3-deoxy-D-arabino-hept-2-ulosonate 7-phosphate $\rightleftharpoons$ 3-dehydroquinate + phosphate

The protein uses NAD⁺ to catalyze the reaction.{{cite journal | vauthors = Hawkins AR, Lamb HK | title = The molecular biology of multidomain proteins. Selected examples | journal = European Journal of Biochemistry | volume = 232 | issue = 1 | pages = 7–18 | date = August 1995 | pmid = 7556173 | doi = 10.1111/j.1432-1033.1995.tb20775.x }}{{cite journal | vauthors = Barten R, Meyer TF | s2cid = 26380973 | title = Cloning and characterisation of the Neisseria gonorrhoeae aroB gene | journal = Molecular & General Genetics | volume = 258 | issue = 1–2 | pages = 34–44 | date = April 1998 | pmid = 9613570 | doi = 10.1007/s004380050704 }} This reaction is part of the shikimate pathway which is involved in the biosynthesis of aromatic amino acids.

3-Dehydroquinate synthase belongs to the family of lyases, to be specific those carbon-oxygen lyases acting on phosphates. This enzyme participates in phenylalanine, tyrosine, and tryptophan biosynthesis. It employs one cofactor, cobalt (Co²⁺).

File:Reaction catalyzed by 3-dehydroquinate synthase.svg

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.{{cite journal | vauthors = Herrmann KM, Weaver LM | title = The Shikimate Pathway | journal = Annual Review of Plant Physiology and Plant Molecular Biology | volume = 50 | pages = 473–503 | date = June 1999 | pmid = 15012217 | doi = 10.1146/annurev.arplant.50.1.473 }} 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.{{cite journal | vauthors = Negron L, Patchett ML, Parker EJ | title = Expression, Purification, and Characterisation of Dehydroquinate Synthase from Pyrococcus furiosus | journal = Enzyme Research | volume = 2011 | pages = 134893 | year = 2011 | pmid = 21603259 | pmc = 3092513 | doi = 10.4061/2011/134893 | doi-access = free }}

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.{{cite journal |last1=Arora Verasztó |first1=H |last2=Logotheti |first2=M |last3=Albrecht |first3=R |last4=Leitner |first4=A |last5=Zhu |first5=H |last6=Hartmann |first6=MD |s2cid=220375879 |title=Architecture and functional dynamics of the pentafunctional AROM complex. |journal=Nature Chemical Biology |date=6 July 2020 |volume=16 |issue=9 |pages=973–978 |doi=10.1038/s41589-020-0587-9 |pmid=32632294}}

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.

File:Cartoon Representation of 3-dehydroquinate synthase.png

File:3-dehydroquinate synthase and its substrates.png

File:Surface representation of 3-dehydroquinate synthase.png

Nomenclature

The systematic name 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).

3-dehydroquinate synthase

Background

Function

Applications

Nomenclature

References

Further reading