Lipoxygenase

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Symbol = Lipoxygenase
Name =

Lipoxygenases (EC number|1.13.11.-) are a family of iron-containing enzymes that catalyse the dioxygenation of polyunsaturated fatty acids in lipids containing a cis,cis-1,4- pentadiene structure. It catalyses the following reaction:

: fatty acid + O₂ = fatty acid hydroperoxide

Lipoxygenases are found in plants, animals and fungi. Products of lipoxygenases are involved in diverse cell functions.

Biological function and classification

These enzymes are most 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 woundingcite journal |author=Vick BA, Zimmerman DC |title=Oxidative systems for the modification of fatty acids |journal= |volume=9 |issue= |pages=53–90 |year=1987] . In mammals a number of lipoxygenases isozymes are involved in the metabolism of prostaglandins and leukotrienescite journal |author=Needleman P, Turk J, Jakschik BA, Morrison AR, Lefkowith JB |title=Arachidonic acid metabolism |journal=Annu. Rev. Biochem. |volume=55 |issue= |pages=69–102 |year=1986 |pmid=3017195 |doi=10.1146/annurev.bi.55.070186.000441] . Sequence data is available for the following lipoxygenases:

3D structure

The crystal structures of soybean and rabbit lipoxygenases are known. The protein consists of a small N-terminal PLAT domain and a major C-terminal catalytic domain (see Pfam link in this article), which contains the active site. In both plant and mammalian enzymes, the N-terminal domain contains an eight-stranded antiparallel β-barrel, but in the soybean lipoxygenases this domain is significantly larger than in the rabbit enzyme. The plant lipoxygenases can be enzymatically cleaved into two fragments which stay tightly associated while the enzyme remains active; separation of the two domains leads to loss of catalytic activity. The C-terminal (catalytic) domain consists of 18-22 helices and one (in rabbit enzyme) or two (in soybean enzymes) antiparallel β-sheets at the opposite end from the N-terminal β-barrel.

Active site

The iron atom in lipoxygenases is bound by four ligands, three of which are histidine residuescite journal |author=Boyington JC, Gaffney BJ, Amzel LM |title=The three-dimensional structure of an arachidonic acid 15-lipoxygenase |journal=Science |volume=260 |issue=5113 |pages=1482–1486 |year=1993 |pmid=8502991 |doi=10.1126/science.8502991] . Six histidines are conserved in all lipoxygenase sequences, five of them are found clustered in a stretch of 40 amino acids. This region contains two of the three zinc-ligands; the other histidines have been showncite journal |author=Steczko J, Donoho GP, Clemens JC, Dixon JE, Axelrod B |title=Conserved histidine residues in soybean lipoxygenase: functional consequences of their replacement |journal=Biochemistry |volume=31 |issue=16 |pages=4053–4057 |year=1992 |pmid=1567851 |doi=10.1021/bi00131a022] to be important for the activity of lipoxygenases.

The two long central helices cross at the active site; both helices include internal stretches of π-helix that provide three histidine (His) ligands to the active site iron. Two cavities in the major domain of soybean lipoxygenase-1 (cavities I and II) extend from the surface to the active site. The funnel-shaped cavity I may function as a dioxygen channel; the long narrow cavity II is presumably a substrate pocket. The more compact mammalian enzyme contains only one boot-shaped cavity (cavity II). In soybean lipoxygenase-3 there is a third cavity which runs from the iron site to the interface of the β-barrel and catalytic domains. Cavity III, the iron site and cavity II form a continuous passage throughout the protein molecule.

The active site iron is coordinated by N^ε of three conserved His residues and one oxygen of the C-terminal carboxyl group. In addition, in soybean enzymes the side chain oxygen of asparagine is weakly associated with the iron. In rabbit lipoxygenase, this Asn residue is replaced with His which coordinates the iron via N^δ atom. Thus, the coordination number of iron is either five or six, with a hydroxyl or water ligand to a hexacoordinate iron.

Biochemical classification

Soybean Lipoxygenase 1 exhibits the largest H/D kinetic isotope effect (KIE) on kcat (kH/kD) (81 near room temperature) so far reported for a biological system.

References

External links

* [http://www.dkfz-heidelberg.de/spec/lox-db/ LOX-DB] - LipOXygenases DataBase
* [http://www.expasy.org/cgi-bin/nicedoc.pl?PDOC00077 Lipoxygenases iron-binding region] in PROSITE
* - structure of lipoxygenase-1 from soybean ("Glycine max")
* - structure of soybean lipoxygenase-3 in complex with (9"Z",11"E",13"S")-13-hydroperoxyoctadeca-9,11-dienoic acid
* - structure of rabbit 15-lipoxygenase in complex with inhibitor
* - animal lipoxygenases
*

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lipoxygenase — (= 5 lipoxygenase; 5 LO) Enzyme that catalyses the addition of a hydroperoxy group to the 5 position of arachidonic acid, the first step in leukotriene synthesis … Dictionary of molecular biology
Lipoxygenase inhibitor — A Lipoxygenase inhibitor is a drug which slows down or stops the action of the lipoxygenase enzyme. More precisely, the term is almost always used to describe an inhibitor of the arachidonate 5 lipoxygenase enzyme, which transforms EFAs into… … Wikipedia
lipoxygenase pathway — a pathway for the formation of leukotrienes and hydroxyeicosatetraenoic acids from arachidonic acid. It is initiated by oxidation of arachidonic acid by arachidonate lipoxygenases, and the reactions occur in the cytosol of leukocytes, mast cells … Medical dictionary
lipoxygenase — noun Any of a class of enzymes that catalyse the oxidation of polyunsaturated fatty acids … Wiktionary
lipoxygenase — A class of enzymes that catalyzes the oxidation of unsaturated fatty acid s with O2 to yield hydroperoxides of the fatty acid s; 5 l. catalyzes the first step in leukotriene biosynthesis, acting on arachidonate. SYN: carotene oxidase, lipoxidase … Medical dictionary
Lipoxygenase — Lip|o|xy|ge|na|se [↑ Lip u. ↑ Oxygenase] Sammelbez. für Nichthäm Eisen Proteine, die als Oxidoreduktasen O2 auf Lipide u. ungesättigte Fettsäuren übertragen; beispielsweise entstehen aus Arachidonsäure auf diese Weise die Leukotriene u. Lipoxine … Universal-Lexikon
lipoxygenase — li·pox·y·gen·ase … English syllables
lipoxygenase — ¦lipˈäksə̇jəˌnās, ¦līp , ˌnāz noun ( s) Etymology: lip + oxygen + ase : lipoxidase … Useful english dictionary

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