Lipoxygenase

Jump to: navigation, search
2p0m.gif
Arachidonate 15-Lipoxygenase
Identifiers
Symbol Lipoxygenase
Pfam PF00305
InterPro IPR013819
SCOP 2sbl
OPM family 87
OPM protein 1zq4
Available PDB structures:

1y4kA:155-823 2sblB:155-823 1fgoA:155-823 1fgmA:155-823 1yge :155-823 1fgtA:155-823 1f8nA:155-823 1fgqA:155-823 1fgrA:155-823 1rrhA:173-841 1rovA:173-841 1lnh :173-841 1no3A:173-841 1n8qA:173-841 1rrlB:173-841 1hu9A:173-841 1ik3A:173-841 1jnqA:173-841 1lox :122-655 1zq4A:498-1058

WikiDoc Resources for

Lipoxygenase

Articles

Most recent articles on Lipoxygenase

Most cited articles on Lipoxygenase

Review articles on Lipoxygenase

Articles on Lipoxygenase in N Eng J Med, Lancet, BMJ

Media

Powerpoint slides on Lipoxygenase

Images of Lipoxygenase

Photos of Lipoxygenase

Podcasts & MP3s on Lipoxygenase

Videos on Lipoxygenase

Evidence Based Medicine

Cochrane Collaboration on Lipoxygenase

Bandolier on Lipoxygenase

TRIP on Lipoxygenase

Clinical Trials

Ongoing Trials on Lipoxygenase at Clinical Trials.gov

Trial results on Lipoxygenase

Clinical Trials on Lipoxygenase at Google

Guidelines / Policies / Govt

US National Guidelines Clearinghouse on Lipoxygenase

NICE Guidance on Lipoxygenase

NHS PRODIGY Guidance

FDA on Lipoxygenase

CDC on Lipoxygenase

Books

Books on Lipoxygenase

News

Lipoxygenase in the news

Be alerted to news on Lipoxygenase

News trends on Lipoxygenase

Commentary

Blogs on Lipoxygenase

Definitions

Definitions of Lipoxygenase

Patient Resources / Community

Patient resources on Lipoxygenase

Discussion groups on Lipoxygenase

Patient Handouts on Lipoxygenase

Directions to Hospitals Treating Lipoxygenase

Risk calculators and risk factors for Lipoxygenase

Healthcare Provider Resources

Symptoms of Lipoxygenase

Causes & Risk Factors for Lipoxygenase

Diagnostic studies for Lipoxygenase

Treatment of Lipoxygenase

Continuing Medical Education (CME)

CME Programs on Lipoxygenase

International

Lipoxygenase en Espanol

Lipoxygenase en Francais

Business

Lipoxygenase in the Marketplace

Patents on Lipoxygenase

Experimental / Informatics

List of terms related to Lipoxygenase


Lipoxygenases (EC 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 wounding[1]. In mammals a number of lipoxygenases isozymes are involved in the metabolism of prostaglandins and leukotrienes[2]. Sequence data is available for the following lipoxygenases:

Rabbit 15-lipoxygenase (blue) with inhibitor (yellow) bound in the active site

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 residues[4]. 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 shown[5] 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 Nε 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 Nδ atom. Thus, the coordination number of iron is either five or six, with a hydroxyl or water ligand to a hexacoordinate iron.

Biochemical classification

EC 1.13.11.12 lipoxygenase (linoleate:oxygen 13-oxidoreductase) linoleate + O2 = (9Z,11E,13S)-13-hydroperoxyoctadeca-9,11-dienoate
EC 1.13.11.31 arachidonate 12-lipoxygenase (arachidonate:oxygen 12-oxidoreductase) arachidonate + O2 = (5Z,8Z,10E,12S,14Z)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
EC 1.13.11.33 arachidonate 15-lipoxygenase (arachidonate:oxygen 15-oxidoreductase) arachidonate + O2 = (5Z,8Z,11Z,13E,15S)-15-hydroperoxyicosa-5,8,11,13-tetraenoate
EC 1.13.11.34 arachidonate 5-lipoxygenase (arachidonate:oxygen 5-oxidoreductase) arachidonate + O2 = leukotriene A4 + H2
EC 1.13.11.40 arachidonate 8-lipoxygenase (arachidonate:oxygen 8-oxidoreductase) arachidonate + O2 = (5Z,8R,9E,11Z,14Z)-8-hydroperoxyicosa-5,9,11,14-tetraenoate

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

  1. Vick BA, Zimmerman DC (1987). "Oxidative systems for the modification of fatty acids" 9: 53-90.
  2. Needleman P, Turk J, Jakschik BA, Morrison AR, Lefkowith JB (1986). "Arachidonic acid metabolism". Annu. Rev. Biochem. 55: 69-102. PMID 3017195.
  3. Tanaka K, Ohta H, Peng YL, Shirano Y, Hibino T, Shibata D (1994). "A novel lipoxygenase from rice. Primary structure and specific expression upon incompatible infection with rice blast fungus". J. Biol. Chem. 269 (5): 3755-3761. PMID 7508918.
  4. Boyington JC, Gaffney BJ, Amzel LM (1993). "The three-dimensional structure of an arachidonic acid 15-lipoxygenase". Science 260 (5113): 1482-1486. PMID 8502991.
  5. Steczko J, Donoho GP, Clemens JC, Dixon JE, Axelrod B (1992). "Conserved histidine residues in soybean lipoxygenase: functional consequences of their replacement". Biochemistry 31 (16): 4053-4057. PMID 1567851.
  1. Tejero, I.; Eriksson, L. A.; Gonzalez-Lafont, A.; Marquet, J.; Lluch, J. M. Hydrogen Abstraction by Soybean Lipoxygenase-1. Density Functional Theory Study on Active Site Models in Terms of Gibbs Free Energies [1]J. Phys. Chem. B, 2004,108, 13831
  • Kulkarni, A.P. (2001). "Lipoxygenase - a versatile biocatalyst for biotransformation of endobiotics and xenobiotics". Cell Mol Life Sci 58: 1805–1825. PMID 11766881..
  • Nelson, M.J. and Seitz, S.P. (1994). "The structure and function of lipoxygenase". Curr Opin Struct Biol 4: 878–884. PMID 8161558..

External links

This article includes text from the public domain Pfam and InterPro IPR001024de:Lipoxygenase



Navigation WikiDoc | WikiPatient | Up To Date Pages | Recently Edited Pages | Recently Added Pictures

Table of Contents In Alphabetical Order | By Individual Diseases | Signs and Symptoms | Physical Examination | Lab Tests | Drugs

Editor Tools Become an Editor | Editors Help Menu | Create a Page | Edit a Page | Upload a Picture or File | Printable version | Permanent link | Maintain Pages | What Pages Link Here
There is no pharmaceutical or device industry support for this site and we need your viewer supported Donations | Editorial Board | Governance | Licensing | Disclaimers | Avoid Plagiarism | Policies
Linked-in.jpg