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Overview for MACiE Entry M0254

Version history

General Information

EC Number: 5.4.99.17 (A member of the Isomerases, Intramolecular transferases, Transferring other groups)

Enzyme Name: squalene-hopene cyclase

Biological Species: Alicyclobacillus acidocaldarius (Bacteria)

Catalytic Chain UniprotKB Accession Codes:

  • P33247 - Squalene--hopene cyclase

Representative PDB Code: 1h3b - SQUALENE-HOPENE CYCLASE (Resolution = 2.80 Å).

Catalytic CATH Codes:

"Other" CATH Codes:

Display structure information

Overall Reaction:

Image of squalene

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Image of hop-22(29)-ene

squalene
C00751
CHEBI:15440
hop-22(29)-ene
C06310
CHEBI:4648

Overall Comment: The major product of this enzyme is hop-22(29)-ene with an 80% yield, represented by KEGG reaction R07322. However, the enzyme also produces hopan-22-ol in a 20% yield, represented by KEGG reaction R07323. The mechanism for the formation of these two products differs only at the final reaction step, for the major product the polarised water deprotonates the final intermediate. For the minor product the polarised water undergoes a nucleophilic addition to the final intermediate.


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Stepwise Description of the Reaction

Step 1Protonation of the terminal double bond by Asp376.
Step 2The intermediate undergoes an intramolecular electrophilic addition in a Markovnikov-type cation–olefin addition.
Step 3The intermediate undergoes an intramolecular electrophilic addition to form the 6.6.6.5 tetracyclic intermediate.
Step 4The initially formed 5-membered ring expands and the final 5-membered ring is formed in an intramolecular electrophilic addition.
Step 5The water molecule polarised by Glu45 abstracts the proton or attacks the E-ring cation, to terminate the reaction.
Step 6Asp376 is reprotonated after turnover via a proton relay chain involving Asp376, Water, Tyr495 and disordered water in the upper cavity of the active site.

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Catalytic Residues Involved

Type Number Chain Location of Function
Asp 376 A Side Chain
His 451 A Side Chain
Tyr 495 A Side Chain
Phe 365 A Side Chain
Tyr 420 A Side Chain
Trp 489 A Side Chain
Tyr 609 A Side Chain
Phe 601 A Side Chain
Phe 605 A Side Chain
Trp 169 A Side Chain
Glu 45 A Side Chain

References

  1. I. Abe (2007), Nat. Prod. Rep., 24, 1311-1331. Enzymatic synthesis of cyclic triterpenes.
    Medline: 18033581
  2. K. U. Wendt et al. (1999), J. Mol. Biol., 286, 175-187. The structure of the membrane protein squalene-hopene cyclase at 2.0 A resolution.
    Medline: 9931258

Homologue information for M0254 (1h3b)

CSA Homologues

MACiE Homologues (within the PDB)

MACiE Homologues (within UniprotKB/SwissProt)


Links to this entry in other databases

Link to EC-PDB-SUM Link to PDB-SUM Link to RCSB PDB Link to PDBe Link to CSA
Link to MetaCyc Link to KEGG Link to BRENDA Link to ExplorENZ

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