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Structure and function of AMP-activated protein kinase

Authors


B. E. Kemp, St Vincent’s Institute, 41 Victoria Parade, Fitzroy, Vic. 3065, Australia. E-mail: bkemp@svi.edu.au

Abstract

AMP-activated protein kinase (AMPK) regulates metabolism in response to energy demand and supply. AMPK is activated in response to rises in intracellular AMP or calcium-mediated signalling and is responsible for phosphorylating a wide variety of substrates. Recent structural studies have revealed the architecture of the αβγ subunit interactions as well as the AMP binding pockets on the γ subunit. The α catalytic domain (1–280) is autoinhibited by a C-terminal tail (313–335), which is proposed to interact with the small lobe of the catalytic domain by homology modelling with the MARK2 protein structure. Two direct activating drugs have been reported for AMPK, the thienopyridone compound A769662 and PTI, which may activate by distinct mechanisms.

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