Identification of a Bromodomain-like Region in 15-Lipoxygenase-1 Explains Its Nuclear Localization.
activity-based probes
bromodomains
inhibitors
lipoxygenases
oxidoreductases
Journal
Angewandte Chemie (International ed. in English)
ISSN: 1521-3773
Titre abrégé: Angew Chem Int Ed Engl
Pays: Germany
ID NLM: 0370543
Informations de publication
Date de publication:
27 09 2021
27 09 2021
Historique:
received:
25
05
2021
pubmed:
14
8
2021
medline:
17
11
2021
entrez:
13
8
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 34388301
doi: 10.1002/anie.202106968
pmc: PMC8518382
doi:
Substances chimiques
Enzyme Inhibitors
0
Arachidonate 15-Lipoxygenase
EC 1.13.11.33
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
21875-21883Informations de copyright
© 2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.
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