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The two reactions compared are done so using a Tanimoto similarity score (for more information, please see the MACiE FAQ) for the bond changes only. The score maay range from 0 to 1 where 1 indicates that the two reactions are identical at the bond change level and 0 indicates that there are no bond changes in common.


Key

1.0-0.9 0.9-0.8 0.8-0.7 0.7-0.6 0.6-0.5 0.5-0.4 0.4-0.3 0.3-0.2 0.2-0.1 0.1-0.0 =0

Results for Comparison of M0106 and M0274

These two reactions have a combined similarity of 0.41


M0106

View
Comparison

M0274

View
EC 1.2.4.1
pyruvate dehydrogenase (acetyl-transferring)
Sub-SubClass EC 1.2.3.3
pyruvate oxidase

Image of [dihydrolipoyllysine-residue acetyltransferase] lipoyllysine

Image of proton

Image of pyruvate

right arrow

Image of carbon dioxide

Image of [dihydrolipoyllysine-residue acetyltransferase] S-acetyldihydrolipoyllysine

[dihydrolipoyllysine-residue acetyltransferase] lipoyllysine
C15972
CHEBI:14919
proton
C00080
CHEBI:24636
pyruvate
C00022
CHEBI:15361
carbon dioxide
C00011
CHEBI:16526
[dihydrolipoyllysine-residue acetyltransferase] S-acetyldihydrolipoyllysine
C16255
0.16

Image of oxygen

Image of phosphate

Image of proton

Image of pyruvate

right arrow

Image of carbon dioxide

Image of acetyl phosphate

Image of hydrogen peroxide

oxygen
C00007
CHEBI:15379
phosphate
C00009
CHEBI:18367
proton
C00080
CHEBI:24636
pyruvate
C00022
CHEBI:15361
carbon dioxide
C00011
CHEBI:16526
acetyl phosphate
C00227
CHEBI:13711
hydrogen peroxide
C00027
CHEBI:16240

Catalytic CATH Codes

3.40.50.970

Catalytic CATH Codes

3.40.50.970

Active Site



0.07526

Active Site



Catalytic Residues

Type Number Chain Location of Function
Glu 59 B Side Chain
His 128 B Side Chain
Arg 267 C Side Chain
His 271 C Side Chain
Tyr 281 C Side Chain
0.0714

Catalytic Residues

Type Number Chain Location of Function
Val 394 A Side Chain
Gln 122 A Side Chain
Phe 479 A Side Chain
Ile 480 A Side Chain
Glu 59 B Side Chain
Phe 121 A Side Chain

Organic Cofactors

Type Identity Chain
Thiamine diphosphate TDP 1370 C

Organic Cofactors

Type Identity Chain
FAD FAD 612 A
Thiamine diphosphate TPP 611 A

Metal Cofactors

Type Het group Number Chain
magnesium MG 1368 C

Metal Cofactors

Type Het group Number Chain
magnesium MG 610 A

Reaction occurs across 8 steps

0.5925

Reaction occurs across 12 steps

Step 1
GIF of Reaction Step M0106.stg01

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.
1 Step 1
GIF of Reaction Step M0274.stg01

Glu59' deprotonates the thiamine diphosphate cofactor at the N1 position. This initiates double bond rearrangement which results in the deprotonation of the N=CH-S group. This activates the cofactor towards electrophilic attack.
Step 2
GIF of Reaction Step M0106.stg02

The carbanion of thiamine diphosphate initiates a nucleophilic attack on the carbonyl carbon of pyruvate in an addition reaction
0.2 Step 2
GIF of Reaction Step M0274.stg02

The carbanion of thiamine diphosphate initiates a nucleophilic attack on the carbonyl carbon of pyruvate in an addition reaction. The conjugated double bond system of the cofactor undergoes rearrangement which results in the deprotonation of Glu59'.
Step 3
GIF of Reaction Step M0106.stg03

The oxyanion formed deprotonates His271C
0 Step 3
GIF of Reaction Step M0274.stg03

The covalently bound pyruvate undergoes decarboxylation.
Step 4
GIF of Reaction Step M0106.stg04

The covalently bound intermediate undergoes decarboxylation.
0 Step 4
GIF of Reaction Step M0274.stg04

A single electron is transferred from the high energy thamine diphosphate enamine intermediate to the FAD, resulting in bond order rearrangement and deprotonation of the alcohol group present on the intermediate.
Step 5
GIF of Reaction Step M0106.stg05

The carbanion formed by decarboxylation initiates a nucleophilic attack on the second substrate in an addition reaction with concomitant deprotonation of His128.
0 Step 5
GIF of Reaction Step M0274.stg05

Tautomerisation of the resulting radical intermediate.
Step 6
GIF of Reaction Step M0106.stg06

His271C deprotonates the hydroxyl in an elimination which reforms the carbanionic form of ThDP and produces the second product.
0 Step 6
GIF of Reaction Step M0274.stg06

The thiamine ring nitrogen acts as an electron sink in the formation of the radical tautomer.
Step 7
GIF of Reaction Step M0106.stg07

The carbanion of the thiamine diphosphate cofactor deprotonates the adjacent amine, which initiates double bond rearrangement that results in the deprotonation of Glu59.
0.11 Step 7
GIF of Reaction Step M0274.stg07

Phosphate initiates a nucleophilic attack on the kinetically stable anion radical adduct.
Step 8
GIF of Reaction Step M0106.stg08

His128 deprotonates water in an inferred return step.
0.33 Step 8
GIF of Reaction Step M0274.stg08

The high energy phosphate radical delivers a second reducing equivalent to the FAD semiquinone.
Step 9
No Step with this number present
N/A Step 9
GIF of Reaction Step M0274.stg09

The tetrahedral anion intermediate collapses. This forms the high energy metabolite acetyl-phosphate.
Step 10
No Step with this number present
N/A Step 10
GIF of Reaction Step M0274.stg10

The FAD diradical transfers one of its electrons to dioxygen with subsequent loss of a single proton.
Step 11
No Step with this number present
N/A Step 11
GIF of Reaction Step M0274.stg11

The FADH transfers the second radical and proton to the dioxygen to regenerate the FAD cofactor and hydrogen peroxide.
Step 12
No Step with this number present
N/A Step 12
GIF of Reaction Step M0274.stg12

The TTP cofactor is regenerated by reprotonation of the C2 position.

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