Jul 14, 2022 · We present cryo-EM structures at 3.0–4.0 Å resolution of phosphorylated human GYS1, in complex with a minimal interacting region of glycogenin, in the inhibited, activated and catalytically...

Apr 1, 2015 · In mammals, there are two glycogen synthase isoforms: muscle glycogen synthase (GYS1; encoded by GYS1), which is ubiquitously expressed, but most abundantly expressed in skeletal and cardiac muscles, and the liver-specific isoform (GYS2; encoded by GYS2).

Jan 17, 2024 · Here, Ullman and colleagues developed a selective inhibitor of glycogen synthase 1 (GYS1) called MZ-101 to reduce glycogen production specifically in skeletal muscle. In a mouse model of Pompe disease, MZ-101 decreased accumulation of glycogen in skeletal muscle to amounts seen with ERT.

Cancer genomics data also indicate that elevated levels of the glycogenic enzymes GYS1/2 or GBE1 (glycogen branching enzyme 1) are associated with poor survival in AML. These results suggest a novel mechanism whereby leukemic cells sustain aberrant proliferation by suppressing excess AMPK activity through elevated glycogenic flux and provide a ...

Jul 14, 2020 · GYS1 promotes ccRCC proliferation in vitro and in vivo. (A) GYS1 was overexpressed by transfection with GYS1 exogenous vector in Caki-1 and Caki-2 cells. The mRNA and protein levels of GYS1 were determined by qRT-PCR and western blotting. (B) EdU assays showed the replication of DNA in cells induced by …

These structures reveal how the enzymes interact to catalyze glycogen synthesis and how glucose-6-phosphate regulates GYS1 activity. Glycogen is the primary energy reserve in mammals, and dysregulation of glycogen metabolism …

Jul 5, 2022 · Full activation of GYS1 widens the GYG1-binding groove, enabling GYG1 release concomitant with glycogen chain growth. This structural mechanism connecting chain nucleation and extension explains the apparent stepwise nature of glycogen synthesis and suggests distinct states to target for GSD-modifying therapeutics.

Gys1 targeting AAV-SaCas9 disrupts the Gys1 gene, reduces Gys1 mRNA and protein levels, and decreases insoluble glycogen and PB accumulation in brains of the Epm2a −/− LD mouse model.

Jan 19, 2025 · Glycogen synthase 1 (GYS1) is the rate-limiting enzyme for glycogen biosynthesis in various tissues, including muscle and the brain [1, 2]. Dysregulation of GYS1 leads to systemic metabolic disorders, such as glycogen storage diseases (GSDs or glycogenoses) [3, 4]. GYS1

We report the successful expression and purification of functional human muscle glycogen synthase (GYS1) in complex with human glycogenin-1 (GN1). Stoichiometric GYS1:GN1 complex was produced by co-expression of GYS1 and GN1 using a bicistronic pFastBac™-Dual expression vector, followed by affinity …