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Entry M0106    1.2.4.1    pyruvate dehydrogenase (acetyl-transferring)

Next Step

Step 01

Glu59 deprotonates the thiamine diphosphate cofactor, which initiates double bond rearrangement that results in the deprotonation of the N=CH-S group, activating the cofactor.

GIF of Reaction Step M0106.stg01


Comment: Activation of the TPP (thiamine diphosphate) cofactor is by the formation of an ionic N1'-H...O bond between the N1' atom of the aminopyrimidine ring of the cofactor and the OG of the intrinsic Glu59, resulting in the transfer of a negative charge from the protein to the cofactor. This transfer then imposes an active V-conformation that brings the N4' atom of the cofactor to the distance required for the intramolecular C2-H...N4' hydrogen bond with the thiazolium C2 atom. This initial activation is then followed by abstraction of the proton from the C2 atom [1]. In order to be analogous to the other thiamine diphosphate activation steps in MACiE, this activation is shown as a single step.



Mechanisms

Proton Transfer

Mechanism Components

Cofactor Used
Bond Formation
Bond Cleavage
Bond Order Change
Intermediate Formation

Amino acids involved in the reaction step.

Amino Acid Location of Function Activity Function
Glu59 Side Chain reactant Hydrogen Bond Acceptor
Proton Acceptor
His128 Side Chain spectator Not Active
Arg267C Side Chain spectator Not Active
His271C Side Chain spectator Not Active
Tyr281C Side Chain spectator Not Active

Organic Cofactors involved in the reaction step

Cofactor Type Cofactor Activity Function
Thiamine diphosphate TDP1370C reactant Hydrogen Bond Acceptor
Hydrogen Bond Donor
Proton Acceptor
Proton Donor
Metal Ligand

Metal Cofactors involved in Step 01

Metal Type Metal Identity Chain Activity Function
magnesium MG 1368 C spectator Cofactor Binding

Reactive Centre

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

View similar reactions in MACiE.


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