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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 M0264 and M0089

These two reactions have a combined similarity of 0.46


M0264

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Comparison

M0089

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EC 2.5.1.21
squalene synthase
Class EC 4.2.3.7
pentalenene synthase

Image of NADPH

Image of 2-trans,6-trans-farnesyl diphosphate

right arrow

Image of proton

Image of NADP

Image of squalene

Image of diphosphate

NADPH
C00005
CHEBI:16908
2 2-trans,6-trans-farnesyl diphosphate
C00448
CHEBI:175763
proton
C00080
CHEBI:24636
NADP
C00006
CHEBI:15846
squalene
C00751
CHEBI:15440
2 diphosphate
C00013
CHEBI:33019
0.37

Image of 2-trans,6-trans-farnesyl diphosphate

right arrow

Image of proton

Image of pentalenene

Image of diphosphate

2-trans,6-trans-farnesyl diphosphate
C00448
CHEBI:175763
proton
C00080
CHEBI:24636
pentalenene
C01841
CHEBI:17251
diphosphate
C00013
CHEBI:18361

Catalytic CATH Codes

1.10.600.10

Catalytic CATH Codes

1.10.600.10

Active Site



0.16362

Active Site



Catalytic Residues

Type Number Chain Location of Function
Tyr 171 A Side Chain
Arg 228 A Side Chain
Arg 218 A Side Chain
Phe 288 A Side Chain
0.1818

Catalytic Residues

Type Number Chain Location of Function
Phe 76 A Side Chain
Phe 77 A Side Chain
Asn 219 A Side Chain
Trp 308 A Side Chain
His 309 A Side Chain

Organic Cofactors

No Associated Organic Cofactors

Organic Cofactors

No Associated Organic Cofactors

Metal Cofactors

Type Het group Number Chain
magnesium No Available PDB Information
magnesium No Available PDB Information
magnesium No Available PDB Information

Metal Cofactors

Type Het group Number Chain
magnesium MG(not in PDB) 1 x

Reaction occurs across 7 steps

0.5882

Reaction occurs across 7 steps

Step 1
GIF of Reaction Step M0264.stg01

Pyrophosphate is eliminated with concomitant deprotonation of Tyr171.
0.2 Step 1
GIF of Reaction Step M0089.stg01

The substrate undergoes heterolysis. The diphosphate product remains associated with the active site, and the cabocation is delocalised over the three terminal carbon atoms of the intermediate.
Step 2
GIF of Reaction Step M0264.stg02

The second molecule of farnesyl diphosphate initiates an electrophilic attack on the intermediate formed.
0.6 Step 2
GIF of Reaction Step M0089.stg02

The terminal double bond adds to the terminal carbocation in an intramolecular electrophilic addition resulting in a cyclic intermediate.
Step 3
GIF of Reaction Step M0264.stg03

Tyr171 acts as a base to deprotonate the intermediate, forming the stable intermediate presqualene diphosphate, the product of the first half reaction.
0.2 Step 3
GIF of Reaction Step M0089.stg03

His309 deprotonates the carbon adjacent to the newly formed carbocation, forming a new double bond in the humulene intermediate.
Step 4
GIF of Reaction Step M0264.stg04

The substrate undergoes heterolysis.
0 Step 4
GIF of Reaction Step M0089.stg04

In a second intramolecular electrophilic addition, a double bond adds across the cycle forming a five membered ring and a new carbocation.
Step 5
GIF of Reaction Step M0264.stg05

A 1,2 sigmatropic rearrangement to produce the cyclobutyl intermediate.
0.2 Step 5
GIF of Reaction Step M0089.stg05

In a third intramolecular electrophilic addition, the remaining double bond adds across the cycle to form the three five membered ring motif of pentalenene, this also causes a [1,2]-hydride shift and the carbocation shifting to a different carbon atom
Step 6
GIF of Reaction Step M0264.stg06

A 1,2 sigmatropic rearrangement to produce the second cyclopropyl intermediate.
0 Step 6
GIF of Reaction Step M0089.stg06

His309 deprotonates the carbon adjacent to the new carbocation, forming the final double bond of pentalenene.
Step 7
GIF of Reaction Step M0264.stg07

A hydride transfer from NADP caused the cleavage of the cyclopropyl group to produce squalene.
0 Step 7
GIF of Reaction Step M0089.stg07

Water deprotonates His309 in an inferred step to regenerate the enzyme active site.

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