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PROSITE documentation PDOC00077

Lipoxygenase iron-binding catalytic domain signatures and profile




Description

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 [1]. In mammals a number of lipoxygenases isozymes are involved in the metabolism of prostaglandins and leukotrienes [2]. Lipoxygenases are also common in primitive animals such as coral [3] 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 1.13.11.12). Plants express a variety of cytosolic isozymes as well as what seems [8] to be a chloroplast isozyme.
  • Mammalian arachidonate 5-lipoxygenase (EC 1.13.11.34).
  • Mammalian arachidonate 12-lipoxygenase (EC 1.13.11.31).
  • Mammalian erythroid cell-specific 15-lipoxygenase (EC 1.13.11.33).
  • Coral (Plexaura homomalla) allene oxide synthase-lipoxygenase protein, a bifunctional enzyme including both a peroxidase and arachidonate 8-lipoxygenase (EC 1.13.11.40).
  • Pseudomonas aeruginosa oleic acid lipoxygenase and arachidonate 15-lipoxygenase (EC 1.13.11.33).

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 [9] 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.

Last update:

July 2008 / Text revised; profile added.

Technical section

PROSITE methods (with tools and information) covered by this documentation:

LIPOXYGENASE_3, PS51393; Lipoxygenase iron-binding catalytic domain profile  (MATRIX)

LIPOXYGENASE_1, PS00711; Lipoxygenases iron-binding region signature 1  (PATTERN)

LIPOXYGENASE_2, PS00081; Lipoxygenases iron-binding region signature 2  (PATTERN)


References

1AuthorsVick B.A., Zimmerman D.C.
Source(In) Biochemistry of plants: A comprehensive treatise, Stumpf P.K., Ed., Vol. 9, pp.53-90, Academic Press, New-York, (1987).

2AuthorsNeedleman P., Turk J., Jakschik B.A., Morrison A.R., Lefkowith J.B.
TitleArachidonic acid metabolism.
SourceAnnu. Rev. Biochem. 55:69-102(1986).
PubMed ID3017195
DOI10.1146/annurev.bi.55.070186.000441

3AuthorsOldham M.L., Brash A.R., Newcomer M.E.
TitleInsights from the X-ray crystal structure of coral 8R-lipoxygenase: calcium activation via a C2-like domain and a structural basis of product chirality.
SourceJ. Biol. Chem. 280:39545-39552(2005).
PubMed ID16162493
DOI10.1074/jbc.M506675200

4AuthorsBusquets M., Deroncele V., Vidal-Mas J., Rodriguez E., Guerrero A., Manresa A.
TitleIsolation and characterization of a lipoxygenase from Pseudomonas 42A2 responsible for the biotransformation of oleic acid into ( S )-( E )-10-hydroxy-8-octadecenoic acid.
SourceAntonie Van Leeuwenhoek 85:129-139(2004).
PubMed ID15028873
DOI10.1023/B:ANTO.0000020152.15440.65

5AuthorsZheng Y., Boeglin W.E., Schneider C., Brash A.R.
TitleA 49-kDa mini-lipoxygenase from Anabaena sp. PCC 7120 retains catalytically complete functionality.
SourceJ. Biol. Chem. 283:5138-5147(2008).
PubMed ID18070874
DOI10.1074/jbc.M705780200

6AuthorsBoyington J.C., Gaffney B.J., Amzel L.M.
TitleThe three-dimensional structure of an arachidonic acid 15-lipoxygenase.
SourceScience 260:1482-1486(1993).
PubMed ID8502991

7AuthorsGillmor S.A., Villasenor A., Fletterick R., Sigal E., Browner M.F.
TitleThe structure of mammalian 15-lipoxygenase reveals similarity to the lipases and the determinants of substrate specificity.
SourceNat. Struct. Biol. 4:1003-1009(1997).
PubMed ID9406550

8AuthorsPeng Y.L., Shirano Y., Ohta H., Hibino T., Tanaka K., Shibata D.
TitleA novel lipoxygenase from rice. Primary structure and specific expression upon incompatible infection with rice blast fungus.
SourceJ. Biol. Chem. 269:3755-3761(1994).
PubMed ID7508918

9AuthorsSteczko J., Donoho G.P., Clemens J.C., Dixon J.E., Axelrod B.
TitleConserved histidine residues in soybean lipoxygenase: functional consequences of their replacement.
SourceBiochemistry 31:4053-4057(1992).
PubMed ID1567851



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