Cofactors

There are no Cofactors for this Enzyme

Reaction Mechanisms

3-dehydroquinate dehydratase (type I) By Reference

3-dehydroquinate dehydratase catalyses the third step in the biosynthesis of chorismate within the Shikimate pathway which synthesises aromatic compounds as well as in the degradative quinate pathway. It is a type I dehydroquinase which catalyses a cis-dehydration of the hexane ring of 3-dehydroquinate via a covalent imine intermediate (unlike the type II dehydroquinase which catalyses a trans-dehydration via an enolate intermediate). Type I dehydroquinases use a Schiff base mechanism. The pathway is essential in microorganisms and plants for the biosynthesis of compounds such as folate, ubiquinone and aromatic amino acids. The absence of this pathway in animals makes it an attractive target for antimicrobial agents.




• Summary
• Step 1
• Step 2
• Step 3
• Step 4
• Step 5
• Step 6
• Step 7
• Step 8
• Step 9
• Products

His143 is thought to play a part as a general acid in the formation of a Schiff base: a covalent adduct between the substrate and Lys170 of the enzyme. The role of the Schiff base is to act as an electron sink . It may also play a role in distorting the carbocyclic ring of dehydroquinate to render it more reactive. His143 is then thought to play a role in proton abstraction. Glu86 is positioned to interact with His143 and orientate it in a manner reminiscent of the serine proteases to allow it to act as a general base and abstract the C2 proton. However it is worth noting that recent research has put some doubt on this role. Any attack on the substrate from below is prevented by a beta-hairpin so only cis-elimination is possible.

Catalytic Residues

AA	Uniprot	Uniprot Resid	PDB	PDB Resid
His	P24670	143	1qfe	143
Lys	P24670	170	1qfe	170
Glu	P24670	86	1qfe	86

Step Components

overall reactant used, proton transfer, unimolecular elimination by the conjugate base, overall product formed, enzyme-substrate complex formation, bimolecular nucleophilic addition, intramolecular elimination, assisted tautomerisation (not keto-enol), intermediate formation, dehydration, schiff base formed, intermediate terminated, native state of enzyme regenerated, inferred reaction step, proton relay, intermediate collapse, enzyme-substrate complex cleavage



Step 1.

Glu86 deprotonates His143, which deprotonates Lys170, activating it.



Step 2.

Lys170 attacks the carbonyl carbon of the substrate in a nucleophilic addition.



Step 3.

A proton is transferred from the covalently attached lysine to the newly formed hydroxide.



Step 4.

Lys170 initiates an elimination of water (which obtains its proton from His143, which deprotonates Glu86) forming the Schiff base intermediate.



Step 5.

Glu86 deprotonates His143, which deprotonates the intermediate at the carbon adjacent to the covalently bound lysine which acts as an electron sink.



Step 6.

Lys170 donates its lone pair of electrons back into the ring, initiating a double bond rearrangement and elimination of water, which obtains its proton from His143, which deprotonates Glu86.



Step 7.

Glu86 deprotonates His143, which deprotonates water, which then attacks the carbon to which Lys170 is covalently attached.



Step 8.

Lys170 deprotonates the hydroxide, which causes Lys170 to be eliminated and the product to be formed.



Step 9.

Lys170 deprotonates His143, which deprotonates Glu86 in an inferred step that returns the enzyme to its starting state.



Products.

The products of the reaction.

View All 2 Reaction Mechanisms in M-CSA

Reaction Parameters

There are no kinetic parameters information for this Enzyme

Associated Proteins

Citations

• in Silico Docking and Molecular Dynamic Simulation of 3-Dehydroquinate Dehydratase from Mycobacterium Tuberculosis Through Virtual Screening and Pharmacokinetics Studies
• Functional Analysis of 3-Dehydroquinate Dehydratase/Shikimate Dehydrogenases Involved in Shikimate Pathway in Camellia sinensis.
• Development of machine learning models to predict inhibition of 3-dehydroquinate dehydratase.
• Prioritization of natural compounds against mycobacterium tuberculosis 3-dehydroquinate dehydratase: A combined in-silico and in-vitro study.
• Binding studies and structure determination of the recombinantly produced type-II 3-dehydroquinate dehydratase from Acinetobacter baumannii.
• Identification of polyketide inhibitors targeting 3-dehydroquinate dehydratase in the shikimate pathway of Enterococcus faecalis.
• Structure-based virtual screening as a tool for the identification of novel inhibitors against Mycobacterium tuberculosis 3-dehydroquinate dehydratase.
• Discovery of Potential Noncovalent Inhibitors of Dehydroquinate Dehydratase from Methicillin-Resistant Staphylococcus aureus through Computational-Driven Drug Design.
• Overexpression of a type II 3-dehydroquinate dehydratase enhances the biotransformation of quinate to 3-dehydroshikimate in Gluconobacter oxydans.
• The MADS-box protein SlTAGL1 regulates a ripening-associated SlDQD/SDH2 involved in flavonoid biosynthesis and resistance against Botrytis cinerea in post-harvest tomato fruit.
• In-silico identification of phytocompounds as inhibitors to two key enzymes of Shikimate pathway of Mycobacterium tuberculosis for discovery of new lead molecule(s) for treatment of Tuberculosis.