Molecular dynamics study on the Apo‐ and Holo‐forms of 5‐lipoxygenase. (7th September 2017)

• Record Type: Journal Article
• Authors: Torras, Juan; Maccarrone, Mauro; Dainese, Enrico
• Other Names: Dainese Enrico guestEditor.; Gilardi Gianfranco guestEditor.; Maccarrone Mauro guestEditor.
• Is Part Of: Biotechnology and applied biochemistry. Volume 65:Number 1(2018)
• Page Start: 54
• Page End: 61
• Publication Date: 2017-09-07
• Subjects: 5‐LOX -- enzyme flexibility -- molecular dynamics; Biotechnology -- Periodicals; Biochemical engineering -- Periodicals; Biochemistry -- Periodicals; Biochemistry -- Periodicals; Genetic Techniques -- Periodicals; Microbiological Techniques -- Periodicals; 660.6
• DOI: 10.1002/bab.1583
• Languages: English
• ISSNs: 0885-4513

Abstract

Abstract: Lipoxygenases (LOXs) are nonheme iron‐containing enzymes catalyzing the dioxygenation of polyunsaturated fatty acids. LOX catalytic activity depends on the presence of iron in the active site and the iron removal is also able to affect the membrane binding properties of the enzyme. Leukotrienes biosynthesis is initiated by the action of 5‐LOX at the level of nuclear membrane and the mechanism of enzyme–membrane interaction is thought to involve structural flexibility and conformational changes at the level of the protein tertiary structure. In this study, we have analyzed by molecular dynamics simulations the conformational changes induced by iron removal in 5‐LOX. The data indicate that the degree of enzyme flexibility is related to the presence of iron into the active site that is able to stabilize the protein increasing its rigidity. These findings provide further evidence that the conformation and the functional activity of LOXs is tuned by the presence of iron at the active site, suggesting new approaches for the design of enzyme inhibitors.