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Entry M0326    2.7.1.40    pyruvate kinase

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Step 02

Thr237 and the Mn(II) cation increase the acidity of water through hydrogen bonding and charge stabilisation, respectively, generating a specific acid to act towards the enolate intermediate.

GIF of Reaction Step M0326.stg02


Comment: A solvent molecule at the active site stereospecifically protonates the enolate at the 2-si face of the double bond to form keto pyruvate. The Thr237 residue has been shown to influence the pKa of the specific acid, and is positioned within the active site to influence the stereo-selectivity of the protonation, although kinetic and pH studies have shown the proton to originate from a solvent molecule [2]. The divalent cation is thought to enhance the acidity of the solvent molecule, rather than the monovalent cation [5].



Mechanisms

Proton Transfer

Mechanism Components

Bond Cleavage
Bond Formation
Bond Order Change
Intermediate Collapse
Overall Product Formed
Intermediate Formation

Amino acids involved in the reaction step.

Amino Acid Location of Function Activity Function
Arg72 Side Chain spectator Attractive Charge Charge Interaction
Electrostatic Stabiliser
Steric Role
Lys269 Side Chain spectator Attractive Charge Charge Interaction
Electrostatic Stabiliser
Steric Role
Arg119 Side Chain spectator Attractive Charge Charge Interaction
Electrostatic Stabiliser
Steric Role
Thr327 Side Chain spectator Hydrogen Bond Donor
Increase Acidity
Electrostatic Stabiliser

Metal Cofactors involved in Step 02

Metal Type Metal Identity Chain Activity Function
potassium K 3532 E spectator Not Active
manganese MG 3534 E spectator Increase Nucleophilicity
Activator
Substrate Binding
none MG 3536 E spectator Not Present

Reactive Centre

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

View similar reactions in MACiE.


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