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Entry M0055    4.2.1.10    3-dehydroquinate dehydratase (type II)

Next Step

Step 01

Tyr28 deprotonates the substrate, forming a double bond and causing the ketone group to reduce and deprotonate water, which in turn deprotonates Asn16.

GIF of Reaction Step M0055.stg01


Comment: The only residue in the correct orientation to perform the proton abstraction is the Tyr28. The hydroxyl of free tyrosine has a pKa of 10.0. However, it is expected that the close proximity of Arg113 and Arg23 sufficiently lowers the pKa of Tyr28 for it to be unprotonated at physiological pH. This behaviour has been seen in other proteins, e.g. human aldose reductase [2]. Asn16, main chain carbonyl of Pro15 and main chain amide of Ala82 hold a conserved water molecule in the correct orientation and position (2.8 Angstroms away) for it to provide the necessary stabilisation of the intermediate formed at the end of this step [2]. Kinetic isotope effects in combination with the structural data suggest that the end product of this step must be the enol, rather than the enolate [2].



Mechanisms

Proton Transfer
Assisted Keto-Enol Tautomerisation

Mechanism Components

Bond Formation
Bond Cleavage
Bond Order Change
Intermediate Formation
Overall Reactant Used
Proton Relay

Amino acids involved in the reaction step.

Amino Acid Location of Function Activity Function
Asn79 Side Chain spectator Hydrogen Bond Acceptor
Arg113 Side Chain spectator Attractive Charge Charge Interaction
Electrostatic Stabiliser
His106 Side Chain spectator Hydrogen Bond Acceptor
Hydrogen Bond Donor
Pro15 Main Chain Carbonyl spectator Hydrogen Bond Acceptor
Activator
Steric Role
Asn16 Side Chain reactant Proton Donor
Hydrogen Bond Donor
Arg23 Side Chain spectator Attractive Charge Charge Interaction
Electrostatic Stabiliser
Tyr28 Side Chain reactant Hydrogen Bond Acceptor
Proton Acceptor
Ala82 Main Chain Amide spectator Hydrogen Bond Donor
Activator
Steric Role
Glu104 Side Chain spectator Hydrogen Bond Donor

Reactive Centre

Bonds Formed Bonds Cleaved Bonds Changed in Order Atom Types Involved
O-H
O-H
O-H
C-H
N-H
O-H
The C-C bond changes from a single to double bond
The C-N bond changes from a single to double bond
The C-O bond changes from a double to single bond
The C-O bond changes from a double to single bond
C
H
N
O

View similar reactions in MACiE.


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