5mcb | pdb_00005mcb
Glycogen phosphorylase in complex with chlorogenic acid.
Structural highlights
Function[PYGM_RABIT] Phosphorylase is an important allosteric enzyme in carbohydrate metabolism. Enzymes from different sources differ in their regulatory mechanisms and in their natural substrates. However, all known phosphorylases share catalytic and structural properties. Publication Abstract from PubMedBACKGROUND: Glycogen phosphorylase (GP) is a pharmaceutical target for the discovery of new antihyperglycaemic agents. Punica granatum is a well-known plant for its potent antioxidant and antimicrobial activities but so far has not been examined for antihyperglycaemic activity. OBJECTIVE: To examine the inhibitory potency of eighteen polyphenolic extracts obtained from Punica granatum fruits and industrial juicing byproducts against GP and discover their most bioactive ingredients. METHOD: Kinetic experiments were conducted to measure the IC50 values of the extracts while affinity crystallography was used to identify the most bioactive ingredient. The inhibitory effect of one of the polyphenolic extracts was also verified ex vivo, in HepG2 cells. RESULTS: All extracts exhibit significant in vitro inhibitory potency (IC50 values in the range of low mug/mL). Affinity crystallography revealed that the most bioactive ingredients of the extracts were chlorogenic and ellagic acids, found bound in the active and the inhibitor site of GP, respectively. While ellagic acid is an established GP inhibitor, the inhibition of chlorogenic acid is reported for the first time. Kinetic analysis indicated that chlorogenic acid is an inhibitor with Ki=2.5 x 10-3 M that acts synergistically with ellagic acid. CONCLUSION: Our study provides the first evidence for a potential antidiabetic usage of Punica granatum extracts as antidiabetic food supplements. Although, more in vivo studies have to be performed before these extracts reach the stage of antidiabetic food supplements our study provides a first positive step towards this process. Affinity crystallography reveals the bioactive compounds of industrial juicing byproducts of Punica granatum for glycogen phosphorylase.,Stravodimos GA, Kantsadi AL, Apostolou A, Kyriakis E, Kafaski-Kanelli VN, Solovou TGA, Gatzona P, Liggri PC, Theofanous S, Gorgogietas VA, Kissa A, Psachoula C, Chatzileontiadou DSM, Lemonakis A, Psarra AG, Skamnaki VT, Haroutounian S, Leonidas DD Curr Drug Discov Technol. 2017 Jun 18. doi: 10.2174/1570163814666170619091736. PMID:28625148[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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