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Catalytic Site Atlas

CSA LITERATURE entry for 1u5u

E.C. namearachidonate 8-lipoxygenase
SpeciesPlexaura homomalla (Black sea rod)
E.C. Number (IntEnz) 1.13.11.40
CSA Homologues of 1u5u3dy5,
CSA Entries With UniProtID O16025
CSA Entries With EC Number 1.13.11.40
PDBe Entry 1u5u
PDBSum Entry 1u5u
MACiE Entry 1u5u

Literature Report

IntroductionCoral allene oxide synthase (cAOS) is a fusion protein with 8R-lipoxygenase (LOX) from Plexura homomalia. cAOS is a hemoprotein with sequence homology to catalase, and is involved in the catalysis of the production of an unstable epoxide (an allene oxide) from the fatty acid hydroperoxide generated by the lipoxygenase activity (8R-HPETE). Despite the sequence homology to catalase, cAOS does not exhibit catalase activity as is does not catalyse the dismutation of hydrogen peroxide to water.
MechansimDespite sequence homology to catalase, the catalytic activities of cAOS and catalase are very different.
8R-HPETE is the fatty acid hydroperoxide derivative of arachidonic acid, produced by LOX activity. cAOS catalyses the conversion of 8R-HPETE into an allene oxide.
1. His 67 hydrogen bonds to the terminal peroxide hydrogen, favouring homolytic cleavage. His 67 hydrogen bonds to Thr 66 and Asn 137, which keeps the distal His imidazole ring in the correct orientation (flipped, relative to in catalase) for enzymatic activity. A hydrogen bond from the main chain amide of Asn 137 also helps to promote this cleavage. 2. Cleavage results in the formation of an alkoxyl radical. One of the peroxide oxygens becomes bound to the heme group as a hydroxyl, with the other oxygen forming the radical. 3. The alkoxyl radical forms a carbon radical, which reduces Fe-IV. Tyr 193 is the site of radical formation, and this residue stabilises coral heme, as well as playing an important role in electron transfer to oxidised heme. 4. The carbon radical is converted into a short-lived epoxy allylic carbocation. 5. This carbocation is deprotonated by His 67 to form the allene oxide.
Reaction

Catalytic Sites for 1u5u

Annotated By Reference To The Literature - Site 1 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
TyrA193193macie:sideChainTyr 193 is the site of radical formation, and acts catalytically by stabilising the heme group and also aiding electron transfer to the oxidised heme.
AsnA137137macie:sideChainAsn 137 hydrogen bonds to His 67 to ensure favourable orientation of the histidine. Hydrogen bonding to the non-terminal peroxide oxygen of the substrate favours homolytic cleavage.
ThrA6666macie:sideChainThr 66 hydrogen bonds to His 67 to ensure favourable orientation of the His imidazole ring.
HisA6767macie:sideChainHis 67 promotes homolyic cleavage by hydrogen bonding to the terminal peroxide oxygen. The position of the His imidazole ring with respect to the heme group is achieved by hydrogen bonds of the His residue to Thr 66 and Asn 137. His 67 also deprotonates the carbocation intermediate to form the allene oxide product.

Annotated By Reference To The Literature - Site 2 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
TyrB193193macie:sideChainTyr 193 is the site of radical formation, and acts catalytically by stabilising the heme group and also aiding electron transfer to the oxidised heme.
AsnB137137macie:sideChainAsn 137 hydrogen bonds to His 67 to ensure favourable orientation of the histidine. Hydrogen bonding to the non-terminal peroxide oxygen of the substrate favours homolytic cleavage.
ThrB6666macie:sideChainThr 66 hydrogen bonds to His 67 to ensure favourable orientation of the His imidazole ring.
HisB6767macie:sideChainHis 67 promotes homolyic cleavage by hydrogen bonding to the terminal peroxide oxygen. The position of the His imidazole ring with respect to the heme group is achieved by hydrogen bonds of the His residue to Thr 66 and Asn 137. His 67 also deprotonates the carbocation intermediate to form the allene oxide product.

Literature References

Notes:
Oldham ML
The structure of coral allene oxide synthase reveals a catalase adapted for metabolism of a fatty acid hydroperoxide.
Proc Natl Acad Sci U S A 2005 102 297-302
PubMed: 15625113
Wu F
Role of radical formation at tyrosine 193 in the allene oxide synthase domain of a lipoxygenase-AOS fusion protein from coral.
Biochemistry 2003 42 6871-6880
PubMed: 12779342
Tosha T
On the relationship of coral allene oxide synthase to catalase. A single active site mutation that induces catalase activity in coral allene oxide synthase.
J Biol Chem 2006 281 12610-12617
PubMed: 16513636
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