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Search The CSA
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Catalytic Site Atlas

CSA LITERATURE entry for 5cox

E.C. nameprostaglandin-endoperoxide synthase
SpeciesMus musculus (Mouse)
E.C. Number (IntEnz) 1.14.99.1
CSA Homologues of 5coxThere are 32 Homologs
CSA Entries With UniProtID Q05769
CSA Entries With EC Number 1.14.99.1
PDBe Entry 5cox
PDBSum Entry 5cox
MACiE Entry M0037

Literature Report

IntroductionProduction of prostaglandin hormones in vertebrates depends on this enzyme, which couples the reduction of dangerous hydroperoxides to the generation of a useful oxidised product. The cofactor which makes this possible is a single iron protoporphyrin IX; its interactions with protein ligands are essential for modulating protein function.
MechansimMutagenesis studies have identified a number of residues essential for catalysis. The replacement of any one of His207, His309 or His388 (numbering for PGH1) by Gln or Ala abolishes both enzyme activities. His388 is the axial ligand for the haem iron, while His 207 is nearby on the distal side. Puzzlingly, His309 is far away from the active site in the structures which are now available. However, Gln203 has also been implicated in the peroxidase activity, cooperating with His207; while Tyr385 has been shown my mutation to be important for the cyclo-oxygenase activity. Spectroscopic data suggest that a tyrosyl radical formed as a result of peroxide reduction abstracts a hydrogen from arachidonate to start the cyclo-oxygenase reaction.
Reaction

Catalytic Sites for 5cox

Annotated By Reference To The Literature - Site 5 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
HisA207193macie:sideChain
TyrA385371macie:sideChain
GlnA203189macie:sideChain

Annotated By Reference To The Literature - Site 6 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
HisB207193macie:sideChain
TyrB385371macie:sideChain
GlnB203189macie:sideChain

Annotated By Reference To The Literature - Site 7 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
HisC207193macie:sideChain
TyrC385371macie:sideChain
GlnC203189macie:sideChain

Annotated By Reference To The Literature - Site 8 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
HisD207193macie:sideChain
TyrD385371macie:sideChain
GlnD203189macie:sideChain

Literature References

Notes:
Kiefer JR
Structural insights into the stereochemistry of the cyclooxygenase reaction.
Nature 2000 405 97-101
PubMed: 10811226
Seibold SA
Peroxidase activity in prostaglandin endoperoxide H synthase-1 occurs with a neutral histidine proximal heme ligand.
Biochemistry 2000 39 6616-6624
PubMed: 10828979
Marnett LJ.
Cyclooxygenase mechanisms.
Curr Opin Chem Biol 2000 4 545-552
PubMed: 11006543
Shimokawa T
Tyrosine 385 of prostaglandin endoperoxide synthase is required for cyclooxygenase catalysis.
J Biol Chem 1990 265 20073-20076
PubMed: 2122967
Shimokawa T
Essential histidines of prostaglandin endoperoxide synthase. His-309 is involved in heme binding.
J Biol Chem 1991 266 6168-6173
PubMed: 1901057
Landino LM
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.
J Biol Chem 1997 272 21565-21574
PubMed: 9261177
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