Document Type
Article
Publication Date
11-25-2005
Abstract
Lipoxygenases (LOXs) catalyze the regio- and stereospecific dioxygenation of polyunsaturated membrane-embedded fatty acids. We report here the 3.2 Å resolution structure of 8R-LOX from the Caribbean sea whip coral Plexaura homomalla, a LOX isozyme with calcium dependence and the uncommon R chiral stereospecificity. Structural and spectroscopic analyses demonstrated calcium binding in a C2-like membrane-binding domain, illuminating the function of similar amino acids in calcium-activated mammalian 5-LOX, the key enzyme in the pathway to the pro-inflammatory leukotrienes. Mutation of Ca2+- ligating amino acids in 8R-LOX resulted not only in a diminished capacity to bind membranes, as monitored by fluorescence resonance energy transfer, but also in an associated loss of Ca2+-regulated enzyme activity. Moreover, a structural basis for R chiral specificity is also revealed; creation of a small oxygen pocket next to Gly428 (Ala in all S-LOX isozymes) promoted C-8 oxygenation with R chirality on the activated fatty acid substrate. © 2005 by The American Society for Biochemistry and Molecular Biology, Inc.
Publication Source (Journal or Book title)
Journal of Biological Chemistry
First Page
39545
Last Page
39552
Recommended Citation
Oldham, M., Brash, A., & Newcomer, M. (2005). Insights from the x-ray crystal structure of coral 8R-lipoxygenase: Calcium activation via a C2-like domain and a structural basis of product chirality. Journal of Biological Chemistry, 280 (47), 39545-39552. https://doi.org/10.1074/jbc.M506675200