Reference: Rudolph MJ, et al. (2010) An inhibited conformation for the protein kinase domain of the Saccharomyces cerevisiae AMPK homolog Snf1. Acta Crystallogr Sect F Struct Biol Cryst Commun 66(Pt 9):999-1002

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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.

Reference Type
Journal Article | Research Support, N.I.H., Extramural
Authors
Rudolph MJ, Amodeo GA, Tong L
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