Crystal structure of pathogenic Staphylococcus aureus lipase complex with the anti-obesity drug orlistat.
Sci Rep
; 10(1): 5469, 2020 03 25.
Article
em En
| MEDLINE
| ID: mdl-32214208
ABSTRACT
Staphylococcus aureus lipase (SAL), a triacylglycerol esterase, is an important virulence factor and may be a therapeutic target for infectious diseases. Herein, we determined the 3D structure of native SAL, the mutated S116A inactive form, and the inhibitor complex using the anti-obesity drug orlistat to aid in drug development. The determined crystal structures showed a typical α/ß hydrolase motif with a dimeric form. Fatty acids bound near the active site in native SAL and inactive S116A mutant structures. We found that orlistat potently inhibits SAL activity, and it covalently bound to the catalytic Ser116 residue. This is the first report detailing orlistat-lipase binding. It provides structure-based information on the production of potent anti-SAL drugs and lipase inhibitors. These results also indicated that orlistat can be repositioned to treat bacterial diseases.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Staphylococcus aureus
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Fármacos Antiobesidade
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Fatores de Virulência
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Inibidores Enzimáticos
/
Esterases
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Reposicionamento de Medicamentos
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Desenvolvimento de Medicamentos
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Orlistate
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Antibacterianos
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
Sci Rep
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Japão