Calcium Binding to 5-Lipoxygenase

Hammarberg, Tove; Reddy, Konda Veera; Persson, Bengt; Rådmark, Olof

doi:10.1007/978-1-4615-0193-0_19

Cited by 6 publications

(1 citation statement)

References 11 publications

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“…At low lipid concentrations and in the absence of Ca 2+ , 5-LO barely exhibits any activity. These data are consistent with previously reported findings that both Ca 2+ ions and phospholipid membranes are crucial for 5-LO function (33,42,43,45,65). Although the data of Skorey and Gresser (44) suggested that at high lipid concentrations (∼350 µM PC) Ca 2+ is not required for 5-LO activity, Reddy et al (45) have shown that Ca 2+ considerably increases 5-LO activity at both low and high PC concentrations, which is in line with our results.…”

Section: Resultssupporting

confidence: 95%

Modulation of Human 5-Lipoxygenase Activity by Membrane Lipids

et al. 2004

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Mammalian 5-lipoxygenase (5-LO) catalyzes the conversion of arachidonic acid (AA) to leukotrienes, potent inflammatory mediators. 5-LO is activated by a Ca(2+)-mediated translocation to membranes, and demonstrates the characteristic features of interfacially activated enzymes, yet the mechanism of membrane binding of 5-LO is not well understood. In an attempt to understand the mechanism of lipid-mediated activation of 5-LO, we have studied the effects of a large set of lipids on human recombinant 5-LO activity, as well as mutual structural effects of 5-LO and membranes. In the presence of 0.35 mM phosphatidylcholine (PC) and 0.2 mM Ca(2+), there was substrate inhibition at >100 microM AA. Data analysis at low AA concentrations yielded the following: K(m) approximately 103 microM and k(cat) approximately 56 s(-1). 5-LO activity was supported by PC more than by any other lipid tested except for a cationic lipid, which was more stimulatory than PC. Binding of 5-LO to zwitterionic and acidic membranes was relatively weak; the extent of binding increased 4-8 times in the presence of Ca(2+), whereas binding to cationic membranes was stronger and essentially Ca(2+)-independent. Polarized attenuated total reflection infrared experiments implied that 5-LO binds to membranes at a defined orientation with the symmetry axis of the putative N-terminal beta-barrel tilted approximately 45 degrees from the membrane normal. Furthermore, membrane binding of 5-LO resulted in dehydration of the membrane surface and was paralleled with stabilization of the structures of both 5-LO and the membrane. Our results provide insight into the understanding of the effects of membrane surface properties on 5-LO-membrane interactions and the interfacial activation of 5-LO.

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Section: Resultssupporting

confidence: 95%

Modulation of Human 5-Lipoxygenase Activity by Membrane Lipids

et al. 2004

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Human 5‐Lipoxygenase

Newcomer

Gilbert

Funk

2012

Encyclopedia of Inorganic and Bioinorganic Chemistry

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The enzyme 5‐lipoxygenase initiates the biosynthesis of leukotrienes, lipid mediators of the inflammatory response. The enzyme is also required for the synthesis of lipoxins, arachidonic‐acid‐derived compounds that promote resolution of inflammation. Lipoxygenases are non‐heme‐iron enzymes that catalyze the peroxidation of polyunsaturated fatty acids. Although all arachidonate‐metabolizing lipoxygenases recognize the same 20‐carbon polyunsaturated fatty acid, each generates a unique product. We describe here the structure of 5‐lipoxygenase, which is distinct among lipoxygenases with respect to the reactions it catalyzes and its regulation. Multiple regulatory mechanisms that combine to ensure a measured generation of its products, precursors of potent signaling compounds, are described. These mechanisms include an atypical (with respect to the lipoxygenase superfamily) protein lability, Ca 2+ ‐induced translocation to the nuclear membrane, and serine phosphorylation.

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