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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 M0240 and M0116

These two reactions have a combined similarity of 0.25


M0240

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Comparison

M0116

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EC 3.5.1.-
histone/protein deacetylase
Class EC 1.6.1.2
NAD(P)+ transhydrogenase (AB-specific)

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
0

Image of NADP

Image of NADH

right arrow

Image of NADPH

Image of NAD

NADP
C00006
CHEBI:18009
NADH
C00004
CHEBI:16908
NADPH
C00005
CHEBI:16474
NAD
C00003
CHEBI:15846

Catalytic CATH Codes

3.40.50.1220
3.30.1600.10

Catalytic CATH Codes

3.40.50.720
3.40.50.1770
3.40.50.1220

Active Site



0.4684

Active Site



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
0.5

Catalytic Residues

Type Number Chain Location of Function
Arg 127 A Side Chain
Asp 135 A Side Chain
Tyr 235 A Side Chain
Asp 132 C Side Chain

Organic Cofactors

No Associated Organic Cofactors

Organic Cofactors

No Associated Organic Cofactors

Metal Cofactors

No Associated Metal Cofactors

Metal Cofactors

No Associated Metal Cofactors

Reaction occurs across 7 steps

0.2083

Reaction occurs across 3 steps

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.
0 Step 1
GIF of Reaction Step M0116.stg01

Asp132C obtains a proton, causing a rearrangement of the active site.
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.
0.05 Step 2
GIF of Reaction Step M0116.stg02

NAD eliminates a hydride ion, which adds to NADP.
Step 3
GIF of Reaction Step M0240.stg03

His135 protonates the lysine nitrogen in the 1',2'-cyclic intermediate.
0 Step 3
GIF of Reaction Step M0116.stg03

Asp132C releases its proton.
Step 4
GIF of Reaction Step M0240.stg04

Lysine dissociates from the 1',2'-cyclic intermediate.
N/A Step 4
No Step with this number present
Step 5
GIF of Reaction Step M0240.stg05

Water, positioned and possibly activated by Asn116, attacks the carbocation.
N/A Step 5
No Step with this number present
Step 6
GIF of Reaction Step M0240.stg06

The product lysine deprotonates the positively-charged oxygen.
N/A Step 6
No Step with this number present
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'.
N/A Step 7
No Step with this number present

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