Open AccessAn inhibited conformation for the protein kinase domain of the Saccharomyces cerevisiae AMPK homolog Snf1
Author(s) -
Rudolph Michael J.,
Amodeo Gabriele A.,
Tong Liang
Publication year - 2010
Publication title -
acta crystallographica section f
Language(s) - English
Resource type - Journals
ISSN - 1744-3091
DOI - 10.1107/s1744309110028265
Subject(s) - ampk , saccharomyces cerevisiae , protein kinase a , chemistry , protein kinase domain , microbiology and biotechnology , domain (mathematical analysis) , biochemistry , kinase , yeast , biology , gene , mutant , mathematical analysis , mathematics
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 (α) 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 (β and γ) subunits. Here, the crystal structure of residues 41–440 of Snf1, which include the KD and AID, is reported at 2.4 Å 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.