Background: 15-Lipoxygenase-2 is linked to atherosclerotic plaque formation; the homologous enzyme 5-lipoxygenase initiates the synthesis of proinflammatory leukotrienes. Results: We determined the crystal structure of 15-LOX-2 in the presence of a substrate mimic. Conclusion: 15-Lipoxygenase-2 and 5-lipoxgenase display active site variations that confer distinct product specificities. Significance: These differences can be exploited for the design of isoform-specific anti-inflammatories.
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