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An inhibited conformation for the protein kinase domain of the Saccharomyces cerevisiae AMPK homolog Snf1.

ABSTRACT: AMP-activated protein kinase (AMPK) is a master metabolic regulator for controlling cellular energy homeostasis. Its homolog in yeast, SNF1, is activated in response to glucose depletion and other stresses. The catalytic (alpha) subunit of AMPK/SNF1 in yeast (Snf1) contains a protein Ser/Thr kinase domain (KD), an auto-inhibitory domain (AID) and a region that mediates interactions with the two regulatory (beta and gamma) subunits. Here, the crystal structure of residues 41-440 of Snf1, which include the KD and AID, is reported at 2.4 A resolution. The AID is completely disordered in the crystal. A new inhibited conformation of the KD is observed in a DFG-out conformation and with the glycine-rich loop adopting a structure that blocks ATP binding to the active site.

SUBMITTER: Rudolph MJ

PROVIDER: S-EPMC2935214 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature

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An inhibited conformation for the protein kinase domain of the Saccharomyces cerevisiae AMPK homolog Snf1.

Rudolph Michael J MJ Amodeo Gabriele A GA Tong Liang L

Acta crystallographica. Section F, Structural biology and crystallization communications 20100821 Pt 9

AMP-activated protein kinase (AMPK) is a master metabolic regulator for controlling cellular energy homeostasis. Its homolog in yeast, SNF1, is activated in response to glucose depletion and other stresses. The catalytic (alpha) subunit of AMPK/SNF1 in yeast (Snf1) contains a protein Ser/Thr kinase domain (KD), an auto-inhibitory domain (AID) and a region that mediates interactions with the two regulatory (beta and gamma) subunits. Here, the crystal structure of residues 41-440 of Snf1, which in ...[more]

PMID: 20823513

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