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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 M0289 and M0240

These two reactions have a combined similarity of 0.29


M0289

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Comparison

M0240

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EC 2.2.1.6
acetolactate synthase
Class EC 3.5.1.-
histone/protein deacetylase

Image of pyruvate

Image of proton

right arrow

Image of carbon dioxide

Image of (S)-2-acetolactate

2 pyruvate
C00022
CHEBI:15361
proton
C00080
CHEBI:15378
CHEBI:24636
carbon dioxide
C00011
CHEBI:16526
(S)-2-acetolactate
C06010
CHEBI:18409
0

Image of Protein acetyllysine

Image of water

Image of NAD

right arrow

Image of Nicotinamide

Image of 2'-O-acetyl ADP-ribose

Image of Protein lysine

Protein acetyllysine
X00123
CHEBI:61930
water
C00001
CHEBI:15377
NAD
C00003
CHEBI:15846
Nicotinamide
C00153
CHEBI:17154
2'-O-acetyl ADP-ribose
X00124
Protein lysine
C02188
CHEBI:29970

Catalytic CATH Codes

3.40.50.970

Catalytic CATH Codes

3.40.50.1220
3.30.1600.10

Active Site



0

Active Site



Catalytic Residues

Type Number Chain Location of Function
Glu 139 A Side Chain
Lys 251 A Side Chain
Gln 202 A Side Chain
Met 582 B Side Chain
0

Catalytic Residues

Type Number Chain Location of Function
His 135 A Side Chain
Arg 45 A Side Chain
Phe 44 A Main Chain Amide
Side Chain
Asp 43 A Main Chain Amide
Pro 42 A Main Chain Carbonyl
Asp 118 A Side Chain
Asn 116 A Side Chain

Organic Cofactors

Type Identity Chain
Thiamine diphosphate TPP 1702 B

Organic Cofactors

No Associated Organic Cofactors

Metal Cofactors

Type Het group Number Chain
magnesium MG 699 A

Metal Cofactors

No Associated Metal Cofactors

Reaction occurs across 6 steps

0.4482

Reaction occurs across 7 steps

Step 1
GIF of Reaction Step M0289.stg01

A glutamate residue 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.
0.09 Step 1
GIF of Reaction Step M0240.stg01

With the aid of nitrogen lone pair donation, the acetyl oxygen of acetyllysine is the nucleophile for nucleophilic attack on the C1' position of NAD+, resulting in a substitution reaction in which nicotinamide is the leaving group. This produces a 1'-O-alkylamidate intermediate.
Step 2
GIF of Reaction Step M0289.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 the glutamate residue.
0.38 Step 2
GIF of Reaction Step M0240.stg02

His135 deprotonates the 3'-hydroxyl of the 1'-O-alkylamidate intermediate, which then itself deprotonates the 2'-hydroxyl. The resulting alkoxide is the nucleophile for intramolecular nucleophilic attack on the acetyl carbon. This produces a 1',2'-cyclic intermediate.
Step 3
GIF of Reaction Step M0289.stg03

The covalently bound pyruvate undergoes decarboxylation.
0 Step 3
GIF of Reaction Step M0240.stg03

His135 protonates the lysine nitrogen in the 1',2'-cyclic intermediate.
Step 4
GIF of Reaction Step M0289.stg04

A second pyruvate molecule approaches the cofactor intermediate in a Si orientation and undergoes electrophilic addition at the carbonanion to give the S enantiomeric acetolacty l-ThDP.
0 Step 4
GIF of Reaction Step M0240.stg04

Lysine dissociates from the 1',2'-cyclic intermediate.
Step 5
GIF of Reaction Step M0289.stg05

The acetolacty l-ThDP intermediate undergoes an intramolecular proton transfer with concurrent elimination of S-acetolactate.
0 Step 5
GIF of Reaction Step M0240.stg05

Water, positioned and possibly activated by Asn116, attacks the carbocation.
Step 6
GIF of Reaction Step M0289.stg06

The TPP cofactor is regenerated by reprotonation of the C2 position.
0.33 Step 6
GIF of Reaction Step M0240.stg06

The product lysine deprotonates the positively-charged oxygen.
Step 7
No Step with this number present
N/A Step 7
GIF of Reaction Step M0240.stg07

The ring of the intermediate is opened when the exocyclic hydroxyl forms a carbonyl, with elimination and subsequent protonation of the endocyclic O1'.

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