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ADP Regulates SNF1, the Saccharomyces cerevisiae Homolog of AMP-Activated Protein Kinase

DOI: 10.1016/j.cmet.2011.09.009 DOI Help
PMID: 22019086 PMID Help

Authors: Faith Mayer (MRC Clinical Sciences Centre, Hammersmith Hospital Campus, Imperial College, DuCane Road, London W12 0NN, UK) , Richard Heath (MRC, National Institute for Medical Research) , Elizabeth Underwood (NIMR) , Matthew Sanders (MRC, National Institute for Medical Research) , David Carmena (MRC Clinical Sciences Centre, Imperial College) , Rhonda r. Mccartney (University of Pittsburgh School of Medicine) , Fiona c. Leiper (MRC Clinical Sciences Centre, Imperial College) , Bing Xiao (MRC National Institute for Medical Research) , Chun Jing (MRC National Institute for Medical Research) , Philip a. Walker (MRC National Institute for Medical Research) , Lesley f. Haire (MRC National Institute for Medical Research) , Roksana Ogrodowicz (MRC National Institute for Medical Research) , Stephen r. Martin (MRC National Institute for Medical Research) , Martin c. Schmidt (University of Pittsburgh School of Medicine) , Steven Gamblin (National Institute for Medical Research, Medical Research Council) , David Carling (MRC Clinical Sciences Centre, Imperial College)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Cell Metabolism , VOL 14 (5) , PAGES 707 - 714

State: Published (Approved)
Published: November 2011
Diamond Proposal Number(s): 7707

Open Access Open Access

Abstract: The SNF1 protein kinase complex plays an essential role in regulating gene expression in response to the level of extracellular glucose in budding yeast. SNF1 shares structural and functional similarities with mammalian AMP-activated protein kinase. Both kinases are activated by phosphorylation on a threonine residue within the activation loop segment of the catalytic subunit. Here we show that ADP is the long-sought metabolite that activates SNF1 in response to glucose limitation by protecting the enzyme against dephosphorylation by Glc7, its physiologically relevant protein phosphatase. We also show that the regulatory subunit of SNF1 has two ADP binding sites. The tighter site binds AMP, ADP, and ATP competitively with NADH, whereas the weaker site does not bind NADH, but is responsible for mediating the protective effect of ADP on dephosphorylation. Mutagenesis experiments suggest that the general mechanism by which ADP protects against dephosphorylation is strongly conserved between SNF1 and AMPK.

Journal Keywords: Adenylate; Amino; Catalytic; Conserved; Enzyme; Gene; Fungal; Glucose; Models; Molecular; Mutation; Phosphorylation; Protein; Protein-Serine-Threonine; Saccharomyces; Saccharomyces; Signal; Substrate; Threonine

Subject Areas: Biology and Bio-materials


Instruments: I02-Macromolecular Crystallography

Added On: 04/03/2013 11:07

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