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Overview for MACiE Entry M0037

Version history

General Information

EC Number: 1.14.99.1 (A member of the Oxidoreductases, Acting on paired donors, with O2 as oxidant and incorporation or reduction of oxygen. The oxygen incorporated need not be derived from O2, Miscellaneous)

Enzyme Name: prostaglandin-endoperoxide synthase

Biological Species: Mus musculus (Mouse)

Catalytic Chain UniprotKB Accession Codes:

  • Q05769 - Prostaglandin G/H synthase 2

Representative PDB Code: 5cox - UNINHIBITED MOUSE CYCLOOXYGENASE-2 (PROSTAGLANDIN SYNTHASE-2) (Resolution = 3.00 Å).

Catalytic CATH Codes:

"Other" CATH Codes:

Display structure information

Overall Reaction:

Image of alkyl peroxide

Image of oxygen

Image of proton

Image of arachidonic acid

right arrow

Image of alcohol

Image of prostaglandin G2

Image of water

alkyl peroxide
X00090
CHEBI:25702
2 oxygen
C00007
CHEBI:15379
2 proton
C00080
CHEBI:24636
arachidonic acid
C00219
CHEBI:32395
alcohol
C00069
CHEBI:30879
prostaglandin G2
C05956
CHEBI:57398
water
C00001
CHEBI:15377

Overall Comment: Tyr385 is sufficiently far from the Gln203 and His207 to be considered to be in a different part of the active site.

The enzyme does not return to a state in which it can catalyse another reaction


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Stepwise Description of the Reaction

Step 1His207 deprotonates the alkyl peroxide, which then coordinates to the Fe(III) centre of the haem cofactor.
Step 2The peroxo bond collapses, donating two electrons to the Fe(III) centre, which immediately shuttles one into the porphyrin ring, creating Fe(IV). The liberated alkoxide deprotonates His207
Step 3The porphyrin radical abstracts a hydrogen from Tyr385.
Step 4Tyr385 abstracts a hydrogen from the arachidonic acid, initiating double bond rearrangement.
Step 5The carbon radical initiates a homolytic attack on a dioxygen molecule in an addition reaction.
Step 6The oxygen radical initiates a homolytic attack on the carbon chain, forming a four-membered ring in an addition reaction. This initiates a second homolytic attack, through double bond rearrangement, which causes the formation of a five-membered carbon rind, and initiates homolytic attack on a second dioxygen molecule in an addition reaction.
Step 7The oxygen radical of the peroxo group abstracts a hydrogen from Tyr385.

View similar reactions (composite manual annotation)


Catalytic Residues Involved

Type Number Chain Location of Function
Gln 203 A Side Chain
His 207 A Side Chain
Tyr 385 A Side Chain

Metal Cofactors for M0037

Type Het group Number Chain
iron HEM 601 A Overview

References

  1. L. J. Marnett (2000), Curr. Opin. Chem. Biol., 4, 545-552. Cyclooxygenase mechanisms.
    Medline: 11006543
  2. L. M. Landino et al. (1997), J. Biol. Chem., 272, 21565-21574. Mutational analysis of the role of the distal histidine and glutamine residues of prostaglandin-endoperoxide synthase-2 in peroxidase catalysis, hydroperoxide reduction, and cyclooxygenase activation.
    Medline: 9261177
  3. M. S. Tang et al. (1997), Biochemistry, 36, 7527-7534. Detection of an Fe2+-protoporphyrin-IX intermediate during aspirin-treated prostaglandin H2 synthase II catalysis of arachidonic acid to 15-HETE.
    Medline: 9200703

Homologue information for M0037 (5cox)

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

GOA logo
peroxidase activity (molecular function)
response to oxidative stress (biological process)
heme binding (molecular function)
oxidation-reduction process (biological process)
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