Linoleate 9S-lipoxygenase

 

Lipoxygenase catalysis is an important aspect of polyunsaturated fatty acid metabolism. The enzyme catalyses the regio- and stereoselective incorporation of molecular oxygen into the methylene interrupted diene system of the substrate to produce a conjugated hydroperoxide product. The peroxidases are intermediates in biosynthetic pathways leading to physiologically potent metabolites in both plants (jasmonates) and animals (leukotrienes and lipoxins). Lipoxygenases contain a distinctive non-heme iron cofactor. Structure is Lipoxygenase 3 from soybean.

 

Reference Protein and Structure

Sequence
P09186 UniProt (1.13.11.58) IPR001246 (Sequence Homologues) (PDB Homologues)
Biological species
Glycine max (Soybean) Uniprot
PDB
1lnh - LIPOXYGENASE-3(SOYBEAN) NON-HEME FE(II) METALLOPROTEIN (2.6 Å) PDBe PDBsum 1lnh
Catalytic CATH Domains
1.20.245.10 CATHdb (see all for 1lnh)
Cofactors
Iron(2+) (1)
Click To Show Structure

Enzyme Reaction (EC:1.13.11.58)

linoleate
CHEBI:30245ChEBI
+
dioxygen
CHEBI:15379ChEBI
→
9(S)-HPODE(1-)
CHEBI:60955ChEBI
Alternative enzyme names: 9-lipoxygenase, 9S-lipoxygenase, Linoleate 9-lipoxygenase, LOX1 (gene name), 9S-LOX,

Enzyme Mechanism

Introduction

The current working hypothesis concerning the mechanism of the catalysed reaction, the iron(III) form combines with substrate to produce a free radical intermediate by a hydrogen tunnelling process. The free radical then combines with molecular oxygen to form a peroxy radical. The iron(II) species obtained in the hydrogen abstraction step transfers an electron to the peroxy radical intermediate, along with proton transfer, to complete the catalysed reaction and regenerate the iron(III) form.

Catalytic Residues Roles

UniProt PDB* (1lnh)
His518, His523, His709, Ile857 His518A, His523A, His709A, Ile857A The Fe(III) ion is coordinated by four ligands, and two potential ligands, providing 3O and 3N atoms. His518, His523 and His709 provide the nitrogen ligands, and Ile857, Asn713 and a water molecule provide the oxygen ligands. This results in an approximately octahedral Fe(III) coordination site, with distorted C3v symmetry.
Asn713 Asn713A Postulated to aid catalysis via hydrogen-bonding. electrostatic stabiliser
*PDB label guide - RESx(y)B(C) - RES: Residue Name; x: Residue ID in PDB file; y: Residue ID in PDB sequence if different from PDB file; B: PDB Chain; C: Biological Assembly Chain if different from PDB. If label is "Not Found" it means this residue is not found in the reference PDB.

Chemical Components

References

  1. Kariapper MS et al. (2001), Biochem Biophys Res Commun, 284, 563-567. Iron Extraction from Soybean Lipoxygenase 3 and Reconstitution of Catalytic Activity from the Apoenzyme. DOI:10.1006/bbrc.2001.5011. PMID:11396936.
  2. Kramer JA et al. (1994), Biochemistry, 33, 15017-15022. Position 713 Is Critical for Catalysis but Not Iron Binding in Soybean Lipoxygenase 3. DOI:10.1021/bi00254a010. PMID:7999759.

Step 1.

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Catalytic Residues Roles

Residue Roles
Asn713A electrostatic stabiliser

Chemical Components

Step 1.

Contributors

Anna Waters, Craig Porter, Gemma L. Holliday