Lipoxygenases (EC 1.13.11.-) are a class of iron-containing dioxygenases which
catalyzes the hydroperoxidation of lipids, containing a cis,cis-1,4-pentadiene structure. The primary products are hydroperoxy fatty acids, which
usually are rapidly reduced to hydroxy derivatives. Lipoxygenases are common
in plants where they may be involved in a number of diverse aspects of plant
physiology including growth and development, pest resistance, and senescence
or responses to wounding . In mammals a number of lipoxygenases isozymes
are involved in the metabolism of prostaglandins and leukotrienes .
Lipoxygenases are also common in primitive animals such as coral  and occur
in some bacteria [4,5]. The N-terminal part of the eukaryotic lipoxygenases
contains a PLAT domain (see <PDOC50095>) that may be involved in
membrane-binding or substrate acquisition, while the iron-binding catalytic
domain forms the C-terminal part.
The 3D structure of the catalytic domain is mainly α-helical with an iron
in the active site (see <PDB:1F8N>). The center of the domain consists of two
long helices, which contain four of the iron-binding residues (at least three
of which are histidines). A fifth residue that coordinates the non-heme
catalytic iron is the carboxylate of the C-terminal isoleucine. The mammalian
catalytic domain has a length of ~550-600 residues, which is shorter than in
the plant lipoxygenases and forms a more compact structure as the additional
100-150 amino acids in plant enzymes form extra loops [3,6,7].
Some proteins known to contain a lipoxygenase iron-binding catalytic domain:
- Plant lipoxygenases (EC 220.127.116.11). Plants express a variety of cytosolic
isozymes as well as what seems  to be a chloroplast isozyme.
- Mammalian arachidonate 5-lipoxygenase (EC 18.104.22.168).
- Mammalian arachidonate 12-lipoxygenase (EC 22.214.171.124).
- Mammalian erythroid cell-specific 15-lipoxygenase (EC 126.96.36.199).
- Coral (Plexaura homomalla) allene oxide synthase-lipoxygenase protein, a
bifunctional enzyme including both a peroxidase and arachidonate
8-lipoxygenase (EC 188.8.131.52).
- Pseudomonas aeruginosa oleic acid lipoxygenase and arachidonate
15-lipoxygenase (EC 184.108.40.206).
Six histidines are strongly conserved in lipoxygenase sequences, five of them
are found clustered in a stretch of 40 amino acids. This region contains two
of the three iron-ligands; the other histidines have been shown  to be
important for the activity of lipoxygenases. As signatures for this family of
enzymes we have selected two patterns in the region of the histidine cluster.
The first pattern contains the first three conserved histidines and the second
pattern includes the fourth and the fifth. We also developed a profile that
covers the entire lipoxygenase iron-binding catalytic domain.
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