Structure conservation in lipoxygenases: Structural analysis of soybean lipoxygenase-1 and modeling of human lipoxygenases

• Published in: Proteins, structure, function, and bioinformatics Vol. 24; no. 3; pp. 275 - 291
• Main Authors: Prigge, Sean T., Boyington, Jeffrey C., Gaffney, Betty J., Amzel, L. Mario
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01-03-1996
• Subjects: 12-lipoxygenases; 15-lipoxygenases; 5-lipoxygenases; Algorithms; Amino Acid Sequence; Animals; Arachidonate 12-Lipoxygenase - chemistry; Arachidonate 12-Lipoxygenase - genetics; Arachidonate 15-Lipoxygenase - chemistry; Arachidonate 15-Lipoxygenase - genetics; arachidonic acid metabolism; Conserved Sequence; Glycine max - enzymology; Glycine max - genetics; homology modeling; Humans; leukotrienes; Ligands; lipoxins; Lipoxygenase - chemistry; Lipoxygenase - genetics; Models, Molecular; Molecular Sequence Data; Molecular Structure; Protein Conformation; Protein Structure, Secondary; Sequence Homology, Amino Acid; side chain placement
• ISSN: 0887-3585; 1097-0134
• DOI: 10.1002/(SICI)1097-0134(199603)24:3<275::AID-PROT1>3.0.CO;2-G

Lipoxygenases are a class of non‐heme iron dioxygenases which catalyze the hydroperoxidation of fatty acids for the biosynthesis of leukotrienes and lipoxins. The structure of the 839‐residue soybean lipoxygenase‐1 was used as a template to model human 5‐, 12‐, and 15‐lipoxygenases. A distance‐based algorithm for placing side chains in a low homology environment (only the four iron ligands were fixed during side chain placement) was devised. Twenty‐six of the 56 conserved lipoxygenase residues were grouped in four distinct regions of the enzyme. These regions were analyzed to discern whether the side chain interactions could be duplicated in the models or whether alternate conformers should be considered. The effects of site directed mutagenesis variants were rationalized using the models of the human lipoxygenases. In particular, variants which shifted positional specificity between 12‐ and 15‐lipoxygenase activity were analyzed. Analysis of active site residues produced a model which accounts for observed lipoxygenase positional specificity and stereospecificity.