D. Grahame Hardie, Fiona A. Ross, Simon A. Hawley Chemistry & Biology

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Presentation transcript:

AMP-Activated Protein Kinase: A Target for Drugs both Ancient and Modern D. Grahame Hardie, Fiona A. Ross, Simon A. Hawley Chemistry & Biology Volume 19, Issue 10, Pages 1222-1236 (October 2012) DOI: 10.1016/j.chembiol.2012.08.019 Copyright © 2012 Elsevier Ltd Terms and Conditions

Chemistry & Biology 2012 19, 1222-1236DOI: (10. 1016/j. chembiol. 2012 Copyright © 2012 Elsevier Ltd Terms and Conditions

Figure 1 Domain Structure of the α, β, and γ Subunits of AMPK and Their Isoforms α-subunits: AID, autoinhibitory domain; α-CTD, C-terminal domain; β-subunits: CBM, carbohydrate-binding module; β-CTD, C-terminal domain; γ subunits: CBS1, CBS2, CBS3, CBS4, cystathione β-synthase repeats; γ2-NTD, N-terminal extension of “long” version of γ2 subunit; γ3-NTD, N-terminal extension of “long” version of γ3 subunit. Chemistry & Biology 2012 19, 1222-1236DOI: (10.1016/j.chembiol.2012.08.019) Copyright © 2012 Elsevier Ltd Terms and Conditions

Figure 2 Acute Metabolic Effects of AMPK Activation Upward/downward arrows indicate that the target protein (inner wheel) or pathway (outer wheel) are activated/inactivated. See text for numbering and key to acronyms. Green arrows on the “spokes” of the wheel indicate activation, red lines with a bar at the end indicate inhibition, and black arrows and “??” indicate that the direct target protein that explains the effect, is not known. Chemistry & Biology 2012 19, 1222-1236DOI: (10.1016/j.chembiol.2012.08.019) Copyright © 2012 Elsevier Ltd Terms and Conditions

Figure 3 Effects of AMPK Activation on Transcription Upward/downward arrows indicate that the target transcription factor or coactivator (inner wheel) or target genes (outer wheel) are activated/inactivated. Note that SIRT1 (on spoke 5) deactylates both FOXO family transcription factors and the transcriptional coactivator PGC-1α. Chemistry & Biology 2012 19, 1222-1236DOI: (10.1016/j.chembiol.2012.08.019) Copyright © 2012 Elsevier Ltd Terms and Conditions

Figure 4 Effects of AMPK Activation Other than on Metabolism and/or Transcription Upward/downward arrows indicate that the functions of the target protein (inner wheel) or target process (outer wheel) are activated/inactivated. Chemistry & Biology 2012 19, 1222-1236DOI: (10.1016/j.chembiol.2012.08.019) Copyright © 2012 Elsevier Ltd Terms and Conditions

Figure 5 Structures of Some AMPK-Activating Compounds and Related Compounds Chemistry & Biology 2012 19, 1222-1236DOI: (10.1016/j.chembiol.2012.08.019) Copyright © 2012 Elsevier Ltd Terms and Conditions