Phosphorylation of AMPK by upstream kinases is required for activity in mammalian cells.

ABSTRACT: AMP-activated protein kinase (AMPK) plays a major role in regulating metabolism and has attracted significant attention as a therapeutic target for treating metabolic disorders. AMPK activity is stimulated more than 100-fold by phosphorylation of threonine 172 (Thr¹⁷²). Binding of AMP to the γ subunit allosterically activates the kinase. Additionally, many small molecules, e.g. 991, have been identified that bind between the kinase domain and the carbohydrate-binding module of the β subunit, stabilising their interaction and leading to activation. It was reported recently that non-phosphorylated Thr¹⁷² AMPK is activated by AMP and A769662. We present here the crystal structure of non-phosphorylated Thr¹⁷² AMPK in complex with AMP and 991. This structure rev

SUBMITTER: Willows R 

PROVIDER: S-EPMC5565919 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature