Overview for MACiE Entry M0037
EC Number: 18.104.22.168 (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).
Display structure information
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 1||His207 deprotonates the alkyl peroxide, which then coordinates to the Fe(III) centre of the haem cofactor.|
|Step 2||The 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 3||The porphyrin radical abstracts a hydrogen from Tyr385.|
|Step 4||Tyr385 abstracts a hydrogen from the arachidonic acid, initiating double bond rearrangement.|
|Step 5||The carbon radical initiates a homolytic attack on a dioxygen molecule in an addition reaction.|
|Step 6||The 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 7||The oxygen radical of the peroxo group abstracts a hydrogen from Tyr385.|
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Catalytic Residues Involved
||Location of Function
Metal Cofactors for M0037
- L. J. Marnett (2000), Curr. Opin. Chem. Biol., 4, 545-552. Cyclooxygenase mechanisms.
- 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.
- 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.
Homologue information for M0037 (5cox)
MACiE Homologues (within the PDB)
MACiE Homologues (within UniprotKB/SwissProt)
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