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Identification of a Bromodomain‐like Region in 15‐Lipoxygenase‐1 Explains Its Nuclear Localization
Author(s) -
Chen Deng,
Xiao Zhangping,
Guo Hao,
Gogishvili Dea,
Setroikromo Rita,
Wouden Petra E.,
Dekker Frank J.
Publication year - 2021
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.202106968
Subject(s) - bromodomain , identification (biology) , lipoxygenase , computational biology , nuclear localization sequence , arachidonate 5 lipoxygenase , microbiology and biotechnology , chemistry , biology , biochemistry , gene , histone , enzyme , nucleus , botany , arachidonic acid
Lipoxygenase (LOX) activity provides oxidative lipid metabolites, which are involved in inflammatory disorders and tumorigenesis. Activity‐based probes to detect the activity of LOX enzymes in their cellular context provide opportunities to explore LOX biology and LOX inhibition. Here, we developed Labelox B as a potent covalent LOX inhibitor for one‐step activity‐based labeling of proteins with LOX activity. Labelox B was used to establish an ELISA‐based assay for affinity capture and antibody‐based detection of specific LOX isoenzymes. Moreover, Labelox B enabled efficient activity‐based labeling of endogenous LOXs in living cells. LOX proved to localize in the nucleus, which was rationalized by identification of a functional bromodomain‐like consensus motif in 15‐LOX‐1. This indicates that 15‐LOX‐1 is not only involved in oxidative lipid metabolism, but also in chromatin binding, which suggests a potential role in chromatin modifications.