3T4N

Structure of the regulatory fragment of Saccharomyces cerevisiae AMPK in complex with ADP

Summary for 3T4N

• Entry DOI: 10.2210/pdb3t4n/pdb
• Descriptor: Carbon catabolite-derepressing protein kinase, SNF1 protein kinase subunit beta-2, Nuclear protein SNF4, ... (5 entities in total)
• Functional Keywords: cbs domain, nucleotide binding, cytosol, protein binding
• Biological source: Saccharomyces cerevisiae (Baker's yeast); More
• Cellular location: Nucleus membrane; Peripheral membrane protein: P06782; Cytoplasm: P34164; Nucleus: P12904
• Total number of polymer chains: 3
• Total formula weight: 70429.99

Authors

Mayer, F.V.,Heath, R.,Underwood, E.,Sanders, M.J.,Carmena, D.,McCartney, R.,Leiper, F.C.,Xiao, B.,Jing, C.,Walker, P.A.,Haire, L.F.,Ogrodowicz, R.,Martin, S.R.,Schmdit, M.C.,Gamblin, S.J.,Carling, D. (deposition date: 2011-07-26, release date: 2011-11-09, Last modification date: 2024-02-28)

Primary citation

Mayer, F.V.,Heath, R.,Underwood, E.,Sanders, M.J.,Carmena, D.,McCartney, R.R.,Leiper, F.C.,Xiao, B.,Jing, C.,Walker, P.A.,Haire, L.F.,Ogrodowicz, R.,Martin, S.R.,Schmidt, M.C.,Gamblin, S.J.,Carling, D.
ADP Regulates SNF1, the Saccharomyces cerevisiae Homolog of AMP-Activated Protein Kinase.
Cell Metab, 14:707-714, 2011

PubMed 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.

PubMed: 22019086
DOI: 10.1016/j.cmet.2011.09.009

Experimental method

X-RAY DIFFRACTION (2.3 Å)