Glycogen synthase (GYS1) is a core enzyme that helps in the production of muscle glycogen, an essential fuel for intense exercise. Production of glycogen is relatively slow and depletion of this important energy store can negatively affect the body’s performance.
The process of glycogen synthesis is inhibited by phosphorylation (which regulates many cellular processes); this can, however, be prevented by using an effector molecule to bind to the protein and regulate enzyme activity.
In this study, Pfizer used cryo-EM at Diamond to determine the high-resolution structures of phosphorylated human GYS1 in complex with an interacting region of glycogenin – an enzyme involved in converting glucose to glycogen. These structures were observed in different states: inhibited, activated, and catalytically competent, to understand the mechanism of GYS1 regulation within the human body.
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