The structure of coral allene oxide synthase reveals a catalase adapted for metabolism of a fatty acid hydroperoxide

Abstract

8R-Lipoxygenase and allene oxide synthase (AOS) are parts of a naturally occurring fusion protein from the coral Plexaura homomalla. AOS catalyses the production of an unstable epoxide (an allene oxide) from the fatty acid hydroperoxide generated by the lipoxygenase activity. Here, we report the structure of the AOS domain and its striking structural homology to catalase. Whereas nominal sequence identity between the enzymes had been previously described, the extent of structural homology observed was not anticipated, given that this enzyme activity had been exclusively associated with the P450 superfamily, and conservation of a catalase fold without catalase activity is unprecedented. Whereas the heme environment is largely conserved, the AOS heme is planar and the distal histidine is flanked by two hydrogen-bonding residues. These critical differences likely facilitate the switch from a catalatic activity to that of a fatty acid hydroperoxidase.eicosanoids ͉ heme

Independent elaboration of steroid hormone signaling pathways in metazoans

“…This could be a CYP from the CYP1 and CYP3 clan (especially CYP3A4), which can aromatize indoline (34), or it may even be a protein from another family. Such an example of convergent evolution has already been described in the case of allene oxide synthase of a coral being able to metabolize a fatty acid peroxide in a way that was previously thought to be specific to CYPs (35). However, aromatization of steroids by these enzymes or a lophotrochozoan enzyme has not been reported.…”

Isolation and Characterization of Two Geometric Allene Oxide Isomers Synthesized from 9S-Hydroperoxylinoleic Acid by Cytochrome P450 CYP74C3

“…Based on the very similar appearance of the double bond protons in the spectra, this generality applies to the allene oxides formed by cytochrome P450 CYP74A (10), by the catalase-related AOS in coral (substrate 8R-hydroperoxyeicosatetraenoic acid) (11,29), and by the catalase-related AOS of the cyanobacterium Acaryochloris marina (substrate 12R-hydroperoxy linolenic acid) (9) (Fig. 7).…”

Cytochrome P450-type Hydroxylation and Epoxidation in a Tyrosine-liganded Hemoprotein, Catalase-related Allene Oxide Synthase

“…Their prototypical activity is the breakdown of hydrogen peroxide, and they also exhibit a weak peroxidatic activity with very small molecule substrates, for example the oxidation of ethanol to acetaldehyde; reaction with larger substrates is precluded by the restricted access to the active site heme (4). Catalase-related allene oxide synthase (cAOS) 2 from the coral Plexaura homomalla is atypical among the tyrosine-liganded hemoproteins in that its natural substrate is a long chain fatty acid hydroperoxide (5). It converts 8R-hydroperoxy-eicosatetraenoic acid (8R-HPETE) to an allene epoxide, an intermediate in cyclopentenone biosynthesis (Fig.…”