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• W2084728352 startingPage "4084" @default.
• W2084728352 abstract "Mammalian 5-lipoxygenase (5-LO) catalyzes conversion of arachidonic acid to leukotrienes, potent mediators of inflammation and allergy. Upon cell stimulation, 5-LO selectively binds to nuclear membranes and becomes activated, yet the mechanism of recruitment of 5-LO to nuclear membranes and the mode of 5-LO-membrane interactions are poorly understood. Here we show that membrane fluidity is an important determinant of membrane binding strength of 5-LO, penetration into the membrane hydrophobic core, and activity of the enzyme. The membrane binding strength and activity of 5-LO increase with the degree of lipid acyl chain cis-unsaturation and reach a plateau with 1-palmitoyl-2-arachidonolyl-sn-glycero-3-phosphocholine (PAPC). A fraction of tryptophans of 5-LO penetrate into the hydrocarbon region of fluid PAPC membranes, but not into solid 1,2-dipalmitoyl-sn-glycero-3-phosphocholine membranes. Our data lead to a novel concept of membrane binding and activation of 5-LO, suggesting that arachidonic-acid-containing lipids, which are present in nuclear membranes at higher fractions than in other cellular membranes, may facilitate preferential membrane binding and insertion of 5-LO through increased membrane fluidity and may thereby modulate the activity of the enzyme. The data presented in this article and earlier data allow construction of a model for membrane-bound 5-LO, including the angular orientation and membrane insertion of the protein." @default.
• W2084728352 created "2016-06-24" @default.
• W2084728352 creator A5012827982 @default.
• W2084728352 creator A5068810331 @default.
• W2084728352 creator A5079864505 @default.
• W2084728352 date "2005-06-01" @default.
• W2084728352 modified "2023-10-03" @default.
• W2084728352 title "Membrane Fluidity Is a Key Modulator of Membrane Binding, Insertion, and Activity of 5-Lipoxygenase" @default.
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• W2084728352 doi "https://doi.org/10.1529/biophysj.104.056788" @default.
• W2084728352 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/1305639" @default.
• W2084728352 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/15778441" @default.
• W2084728352 hasPublicationYear "2005" @default.
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