Lipoxygenase 2 from Cyanothece sp. controls dioxygen insertion by steric shielding and substrate fixation

Abstract The biological function of lipoxygenases depends on the regio and stereo specific formation of fatty acid-derived hydroperoxides and different concepts exist to explain the mechanism that directs dioxygen to a specific carbon atom within the substrate. Here, we report the 1.8 Å resolution c...

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Autores principales:	Julia Newie, Piotr Neumann, Martin Werner, Ricardo A. Mata, Ralf Ficner, Ivo Feussner
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/984ebb9695be482e9b12126648e01635
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spelling	oai:doaj.org-article:984ebb9695be482e9b12126648e016352021-12-02T12:32:30ZLipoxygenase 2 from Cyanothece sp. controls dioxygen insertion by steric shielding and substrate fixation10.1038/s41598-017-02153-w2045-2322https://doaj.org/article/984ebb9695be482e9b12126648e016352017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-02153-whttps://doaj.org/toc/2045-2322Abstract The biological function of lipoxygenases depends on the regio and stereo specific formation of fatty acid-derived hydroperoxides and different concepts exist to explain the mechanism that directs dioxygen to a specific carbon atom within the substrate. Here, we report the 1.8 Å resolution crystal structure of a cyanobacterial lipoxygenase that produces bis-allylic hydroperoxides (CspLOX2). Site directed mutagenesis experiments combined with computational approaches reveal that residues around the active site direct dioxygen to a preferred carbon atom and stereo configuration in the substrate fatty acid. Modulating the cavity volume around the pentadiene system of linoleic acid shifted the product formation towards 9S-, 9R-, 13S- or 13R-hydroperoxides in correlation with the site of mutation, thus decreasing the amount of the bis-allylic 11R-hydroperoxide. Decreasing the channel size of a 9R-lipoxygenase (CspLOX1) on the other hand could in turn induce formation of the bis-allylic 11R-hydroperoxide. Together this study suggests that an active site clamp fixing the pentadiene system of the substrate together with steric shielding controls the stereo and regio specific positioning of dioxygen at all positions of the reacting pentadiene system of substrate fatty acids.Julia NewiePiotr NeumannMartin WernerRicardo A. MataRalf FicnerIvo FeussnerNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Julia Newie Piotr Neumann Martin Werner Ricardo A. Mata Ralf Ficner Ivo Feussner Lipoxygenase 2 from Cyanothece sp. controls dioxygen insertion by steric shielding and substrate fixation
description	Abstract The biological function of lipoxygenases depends on the regio and stereo specific formation of fatty acid-derived hydroperoxides and different concepts exist to explain the mechanism that directs dioxygen to a specific carbon atom within the substrate. Here, we report the 1.8 Å resolution crystal structure of a cyanobacterial lipoxygenase that produces bis-allylic hydroperoxides (CspLOX2). Site directed mutagenesis experiments combined with computational approaches reveal that residues around the active site direct dioxygen to a preferred carbon atom and stereo configuration in the substrate fatty acid. Modulating the cavity volume around the pentadiene system of linoleic acid shifted the product formation towards 9S-, 9R-, 13S- or 13R-hydroperoxides in correlation with the site of mutation, thus decreasing the amount of the bis-allylic 11R-hydroperoxide. Decreasing the channel size of a 9R-lipoxygenase (CspLOX1) on the other hand could in turn induce formation of the bis-allylic 11R-hydroperoxide. Together this study suggests that an active site clamp fixing the pentadiene system of the substrate together with steric shielding controls the stereo and regio specific positioning of dioxygen at all positions of the reacting pentadiene system of substrate fatty acids.
format	article
author	Julia Newie Piotr Neumann Martin Werner Ricardo A. Mata Ralf Ficner Ivo Feussner
author_facet	Julia Newie Piotr Neumann Martin Werner Ricardo A. Mata Ralf Ficner Ivo Feussner
author_sort	Julia Newie
title	Lipoxygenase 2 from Cyanothece sp. controls dioxygen insertion by steric shielding and substrate fixation
title_short	Lipoxygenase 2 from Cyanothece sp. controls dioxygen insertion by steric shielding and substrate fixation
title_full	Lipoxygenase 2 from Cyanothece sp. controls dioxygen insertion by steric shielding and substrate fixation
title_fullStr	Lipoxygenase 2 from Cyanothece sp. controls dioxygen insertion by steric shielding and substrate fixation
title_full_unstemmed	Lipoxygenase 2 from Cyanothece sp. controls dioxygen insertion by steric shielding and substrate fixation
title_sort	lipoxygenase 2 from cyanothece sp. controls dioxygen insertion by steric shielding and substrate fixation
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/984ebb9695be482e9b12126648e01635
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Lipoxygenase 2 from Cyanothece sp. controls dioxygen insertion by steric shielding and substrate fixation

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