title: 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.
authors.affiliation: Department of Biological Sciences, Columbia University, New York, NY 10027, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Rudolph
authors.forename: Gabriele A
authors.initials: GA
authors.lastname: Amodeo
authors.forename: Liang
authors.initials: L
authors.lastname: Tong
mesh_terms: D000595:Amino Acid Sequence; D018360:Crystallography, X-Ray; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry*; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000201:enzymology*; D016415:Sequence Alignment
chemical_list: C071570:SNF1-related protein kinases; D017346:Protein Serine-Threonine Kinases
references.citation: Biochem Soc Trans. 2003 Feb;31(Pt 1):178-81
references.pmid: 12546680
references.citation: Biochem Biophys Res Commun. 2005 Dec 2;337(4):1224-8
references.pmid: 16236260
references.citation: J Biol Chem. 2007 Jan 5;282(1):495-506
references.pmid: 17088252
references.citation: Acta Crystallogr D Biol Crystallogr. 2001 Aug;57(Pt 8):1127-34
references.pmid: 11468396
references.citation: Methods Enzymol. 1997;276:307-26
references.pmid: 27754618
references.citation: J Biol Chem. 1998 Dec 25;273(52):35347-54
references.pmid: 9857077
references.citation: Nat Struct Biol. 2002 Apr;9(4):268-72
references.pmid: 11896401
references.citation: Acta Crystallogr A. 1991 Mar 1;47 ( Pt 2):110-9
references.pmid: 2025413
references.citation: Annu Rev Biochem. 1998;67:821-55
references.pmid: 9759505
references.citation: Nature. 2009 Jun 25;459(7250):1146-9
references.pmid: 19474788
references.citation: Biochem Soc Trans. 2003 Feb;31(Pt 1):162-8
references.pmid: 12546677
references.citation: Methods Enzymol. 1997;276:171-9
references.pmid: 9048376
references.citation: Nat Rev Mol Cell Biol. 2007 Oct;8(10):774-85
references.pmid: 17712357
references.citation: Cell Metab. 2005 Jan;1(1):15-25
references.pmid: 16054041
references.citation: Structure. 2006 Mar;14(3):477-85
references.pmid: 16531232
references.citation: Genes Dev. 1996 Dec 15;10(24):3105-15
references.pmid: 8985180
references.citation: Acta Crystallogr D Biol Crystallogr. 1997 May 1;53(Pt 3):240-55
references.pmid: 15299926
references.citation: Acta Crystallogr D Biol Crystallogr. 1998 Sep 1;54(Pt 5):905-21
references.pmid: 9757107