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PDBsum entry 3cli
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References listed in PDB file
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Key reference
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Title
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Structural insights into the evolutionary paths of oxylipin biosynthetic enzymes.
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Authors
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D.S.Lee,
P.Nioche,
M.Hamberg,
C.S.Raman.
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Ref.
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Nature, 2008,
455,
363-368.
[DOI no: ]
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PubMed id
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Abstract
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The oxylipin pathway generates not only prostaglandin-like jasmonates but also
green leaf volatiles (GLVs), which confer characteristic aromas to fruits and
vegetables. Although allene oxide synthase (AOS) and hydroperoxide lyase are
atypical cytochrome P450 family members involved in the synthesis of jasmonates
and GLVs, respectively, it is unknown how these enzymes rearrange their
hydroperoxide substrates into different products. Here we present the crystal
structures of Arabidopsis thaliana AOS, free and in complex with substrate or
intermediate analogues. The structures reveal an unusual active site poised to
control the reactivity of an epoxyallylic radical and its cation by means of
interactions with an aromatic pi-system. Replacing the amino acid involved in
these steps by a non-polar residue markedly reduces AOS activity and,
unexpectedly, is both necessary and sufficient for converting AOS into a GLV
biosynthetic enzyme. Furthermore, by combining our structural data with
bioinformatic and biochemical analyses, we have discovered previously unknown
hydroperoxide lyase in plant growth-promoting rhizobacteria, AOS in coral, and
epoxyalcohol synthase in amphioxus. These results indicate that oxylipin
biosynthetic genes were present in the last common ancestor of plants and
animals, but were subsequently lost in all metazoan lineages except Placozoa,
Cnidaria and Cephalochordata.
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Figure 1.
Figure 1: Reactions catalysed by the CYP74 enzyme family. In
higher plants, C[18] fatty acids (linoleic and linolenic acids)
are oxygenated at either position 9 or 13 by lipoxygenases to
yield hydroperoxides. Subsequently, these are converted by
allene oxide synthase (AOS, also known as CYP74A), hydroperoxide
lyase (HPL, also known as CYP74B) and divinyl ether synthase
(DES, also known as CYP74D) to allene oxide (an essential
intermediate in jasmonate biosynthesis), green leaf volatiles
(aldehydes) and divinyl ethers, respectively. For clarity, only
13-hydroperoxide-derived metabolites are shown. 12,13(S)-allene
oxide, 12,13S-epoxy-9Z,11,15Z-octadecatrienoic acid; 13(S)-HPOT,
13S-hydroperoxyoctadecatrienoic acid;  -ketol
is the hydrolytic product of the highly unstable allene oxide;
hemiacetal, hydroxyhexenyloxydodecadienoic acid.
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Figure 4.
Figure 4: Proposed reaction paths for AOS and HPL on the basis
of the current structural and enzymological studies^14, ^15,
^16, ^17, ^21. The intermediate epoxyallylic radical formed
in step 4 can either undergo one electron oxidation followed by
proton loss (AOS) or oxygen rebound (HPL). The structure of the
peroxide substrate is abbreviated to highlight the region
undergoing chemical transformation. For clarity, the Fe–S bond
between the haem iron and Cys 471 is only shown in step 1. It
remains intact throughout the catalytic cycle. Hydrogen bonds
are illustrated with blue dashed lines.
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nature
(2008,
455,
363-368)
copyright 2008.
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