Structure and function of AMP-activated protein kinase

• Published in: Acta Physiologica Vol. 196; no. 1; pp. 3 - 14
• Main Authors: Oakhill, J.S, Scott, J.W, Kemp, B.E
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Oxford, UK Oxford, UK : Blackwell Publishing Ltd 01.05.2009; Blackwell Publishing Ltd; Wiley-Blackwell
• Subjects: Adenosine Monophosphate - metabolism; Amino Acid Sequence; AMP; AMP-Activated Protein Kinases - chemistry; AMP-Activated Protein Kinases - genetics; AMP-Activated Protein Kinases - metabolism; AMPK; Animals; Binding Sites; Biological and medical sciences; drugs; Enzyme Activation; Fundamental and applied biological sciences. Psychology; Models, Molecular; Molecular Sequence Data; Molecular Structure; Protein Conformation; Protein Subunits - chemistry; Protein Subunits - genetics; Protein Subunits - metabolism; regulation; Signal Transduction - physiology; structure; subunits; Vertebrates: anatomy and physiology, studies on body, several organs or systems; subunits; Vertebrata; Mammalia; AMP; regulation; Enzyme; drugs; Transferases; Non-specific serine/threonine protein kinase; AMPK; Subunit; Structure
• ISSN: 1748-1708; 1748-1716
• DOI: 10.1111/j.1748-1716.2009.01977.x

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.