Selective protein unfolding: a universal mechanism of action for the development of irreversible inhibitors.
Chem Commun (Camb)
; 54(14): 1738-1741, 2018 Feb 13.
Article
em En
| MEDLINE
| ID: mdl-29376540
ABSTRACT
High-throughput differential scanning fluorimetry of GFP-tagged proteins (HT-DSF-GTP) was applied for the identification of novel enzyme inhibitors acting by a mechanism termed selective protein unfolding (SPU). Four different protein targets were interrogated with the same library to identify target-selective hits. Several hits selectively destabilized bacterial biotin protein ligase. Structure-activity relationship data confirmed a structure-dependent mechanism of protein unfolding. Simvastatin and altenusin were confirmed to irreversibly inactivate biotin protein ligase. The principle of SPU combined with HT-DSF-GTP affords an invaluable and innovative workflow for the identification of new inhibitors with potential applications as antimicrobials and other biocides.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteínas de Fluorescência Verde
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Inibidores Enzimáticos
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Desdobramento de Proteína
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Ligases
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article