| Root |
Created: 25 April 1997
| Enzyme | Mononuclear iron centre | Iron ligand(s) | Formal iron oxidation/spin states |
|---|---|---|---|
| Plant |
 His)3OCOO¯IleO AsnOH |
His;
OH¯, H2O or other ligand |
FeII (S = 2);
FeIII (S = 5/2) |
| Mammalian |
His)3NHisOCOO¯IleOH |
His;
N OH¯, H2O or other ligand |
Lipoxygenases are mononuclear iron enzymes that catalyse the dioxygenation of
polyunsaturated fatty acids in reaction (1):
Lipoxygenases are found in plants and in animals
[1-3].
Products of plant and animal lipoxygenases are involved in diverse cell
functions (see list of reviews on structure
and function of lipoxygenases).
(1)
The 3D structures of soybean [4,
5] and rabbit
[6] lipoxygenases are known.
The protein consists of a small Nterminal domain and a major
Cterminal domain, which contains the active site.
In both plant and mammalian enzymes, the Nterminal domain contains an
eightstranded antiparallel ßbarrel, but in the soybean
lipoxygenases this domain is significantly larger than in the rabbit enzyme.
It has been noted that the ßbarrel domain of mammalian lipoxygenase
is more similar in sequence, size and structure to an analogous Cterminal
ßbarrel domain in the mammalian lipases than to the homologous
domain in plant lipoxygenases [6].
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
[7]. The Cterminal (catalytic)
domain consists of 18-22 helices and one (in rabbit enzyme) or two
(in soybean enzymes) antiparallel ßsheets at the opposite end from
the Nterminal ßbarrel.
The two long central helices cross at the active site; both helices include
internal stretches of 
helix that
provide three His ligands to the active site iron. Two cavities in the major
domain of soybean lipoxygenase1 (cavities I and II) extend from the
surface to the active site. The funnelshaped 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 bootshaped cavity
(cavity II) [6].
The role of conserved residues of cavity II in the positional specificity
of fatty acid dioxygenation has been examined by sitedirected mutagenesis
[8; 1,
2 and references therein].
In soybean lipoxygenase3 there is a third cavity which
runs from the iron site to the interface of the ßbarrel
and catalytic domains. Cavity III, the iron site and cavity II form a
continuous passage throughout the protein molecule
[5].
The active site iron is coordinated by
N
of three conserved
His residues and one oxygen of the Cterminal carboxyl group; in addition,
in soybean enzymes the side chain oxygen of Asn is weakly associated with
the iron. In rabbit lipoxygenase, this Asn residue is replaced with His which
coordinates the iron via
N.
Thus, the coordination number of iron is either five or six, with a hydroxyl
or water ligand to a hexacoordinate iron
(see Figure 2SBL b).
The table below lists the mononuclear iron environment residues in known
3D structures.
| Enzyme | Mononuclear iron environment residues | PDB code | Ref. | ||||
|---|---|---|---|---|---|---|---|
| ENZYME | LIGAND | BRENDA | Official name | Alternative names |
|---|---|---|---|---|
| 1.13.11.12 | 1.13.11.12 | 1.13.11.12 | Lipoxygenase | Carotene oxidase; lipoxidase |
| 1.13.11.31 | 1.13.11.31 | 1.13.11.31 | Arachidonate 12lipoxygenase | 12 lipoxygenase |
| 1.13.11.33 | 1.13.11.33 | 1.13.11.33 | Arachidonate 15lipoxygenase | Arachidonate  6 lipoxygenase;
linoleic acid 6 lipoxygenase;
15lipoxygenase |
| 1.13.11.34 | 1.13.11.34 | 1.13.11.34 | Arachidonate 5lipoxygenase | LeukotrieneA4 synthase; 5lipoxygenase |
| 1.13.11.40 | 1.13.11.40 | 1.13.11.40 | Arachidonate 8lipoxygenase | Arachidonate 8Rlipoxygenase |
| PRINTS ID | PRINTS AC | PROSITE/BLOCKS ID | PROSITE AC | BLOCKS AC |
|---|---|---|---|---|
| LIPOXYGENASE | PR00087 | LIPOXYGENASE_1 LIPOXYGENASE_2 |
PS00711
PS00081 |
BL00711 |
| MAMLPOXGNASE | PR00467 | |||
| PLTLPOXGNASE | PR00468 |
| Protein Superfamily | Pfam | LPFC 3D alignment |
|---|---|---|
|
00182;
lipoxygenase
00183; arachidonate 5lipoxygenase |
| PDB | scop | BSM | RELI Base | Header | 
¹ | 1lnh | 1lnh | 1lnh | 1lnh | Lipoxygenase3; soybean (Glycine max) |
|---|---|---|---|---|---|
| 1yge | 1yge | 1yge | 1yge | Lipoxygenase1 (100 K); soybean (Glycine max) | |
| 2sbl | 2sbl | 2sbl | 2sbl | Lipoxygenase1; soybean (Glycine max) | MMS94164 |
¹ Macromolecular Structures abstract.
Full text is available to BioMedNet
Members
References
Acknowledgements
We thank Kutbuddin S. Doctor
(Johns Hopkins University, Baltimore, USA) for his comments and corrections
to this entry.
| Bibliography on structural studies of lipoxygenases |
|
| Reviews on lipoxygenases |
1OCOO¯Ile;