Affinity Crystallography Reveals Binding of Pomegranate Juice Anthocyanins at the Inhibitor Site of Glycogen Phosphorylase: The Contribution of a Sugar Moiety to Potency and Its Implications to the Binding Mode.
J Agric Food Chem
; 68(37): 10191-10199, 2020 Sep 16.
Article
em En
| MEDLINE
| ID: mdl-32840370
ABSTRACT
Anthocyanins (ACNs) are dietary phytochemicals with an acknowledged therapeutic significance. Pomegranate juice (PJ) is a rich source of ACNs with potential applications in nutraceutical development. Glycogen phosphorylase (GP) catalyzes the first step of glycogenolysis and is a molecular target for the development of antihyperglycemics. The inhibitory potential of the ACN fraction of PJ is assessed through a combination of in vitro assays, ex vivo investigation in hepatic cells, and X-ray crystallography studies. The ACN extract potently inhibits muscle and liver isoforms of GP. Affinity crystallography reveals the structural basis of inhibition through the binding of pelargonidin-3-O-glucoside at the GP inhibitor site. The glucopyranose moiety is revealed as a major determinant of potency as it promotes a structural binding mode different from that observed for other flavonoids. This inhibitory effect of the ACN scaffold and its binding mode at the GP inhibitor binding site may have significant implications for future structure-based drug design endeavors.
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Base de dados:
MEDLINE
Assunto principal:
Extratos Vegetais
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Glicogênio Fosforilase
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Inibidores Enzimáticos
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Sucos de Frutas e Vegetais
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Punica granatum
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Antocianinas
Idioma:
En
Revista:
J Agric Food Chem
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Grécia