2qlv | pdb_00002qlv

Crystal structure of the heterotrimer core of the S. cerevisiae AMPK homolog SNF1

spinqualitylabelsall models 2qlv, resolution 2.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2qlv is a 6 chain structure with sequence from Atcc 18824. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Gene: SNF1, CAT1, CCR1, GLC2, PAS14 (ATCC 18824), SIP2, SPM2 (ATCC 18824), SNF4, CAT3 (ATCC 18824) Activity: Non-specific serine/threonine protein kinase, with EC number 2.7.11.1 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [SNF1_YEAST] Essential for release from glucose repression. It interacts and has functional relationship to the regulatory protein SNF4. Could phosphorylate CAT8. Phosphorylates histone H3 to form H3S10ph, which promotes H3K14ac formation, and which is required for transcriptional activation through TBP recruitment to the promoters. [AAKG_YEAST] Adenine nucleotides-binding subunit gamma of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism. In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation. AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators. Gamma non-catalytic subunit mediates binding to AMP, ADP and ATP, leading to activate or inhibit AMPK: AMP-binding results in allosteric activation of alpha catalytic subunit (SNF1) both by inducing phosphorylation and preventing dephosphorylation of catalytic subunits. [SIP2_YEAST] Beta subunit of the SNF1 kinase complex, which is required for transcriptional, metabolic, and developmental adaptations in response to glucose limitation. Has a structural role, mediating heterotrimer formation, and a regulatory role, defining carbon source-regulated subcellular location and substrate specificity of the SNF1 kinase complex. Involved in the regulation of aging. Acts as a negative regulator of nuclear SNF1 activity in young cells by sequestering its activating gamma subunit at the plasma membrane. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed AMP-activated protein kinase (AMPK) is a central regulator of energy homeostasis in mammals and is an attractive target for drug discovery against diabetes, obesity and other diseases. The AMPK homologue in Saccharomyces cerevisiae, known as SNF1, is essential for responses to glucose starvation as well as for other cellular processes, although SNF1 seems to be activated by a ligand other than AMP. Here we report the crystal structure at 2.6 A resolution of the heterotrimer core of SNF1. The ligand-binding site in the gamma-subunit (Snf4) has clear structural differences from that of the Schizosaccharomyces pombe enzyme, although our crystallographic data indicate that AMP can also bind to Snf4. The glycogen-binding domain in the beta-subunit (Sip2) interacts with Snf4 in the heterotrimer but should still be able to bind carbohydrates. Our structure is supported by a large body of biochemical and genetic data on this complex. Most significantly, the structure reveals that part of the regulatory sequence in the alpha-subunit (Snf1) is sequestered by Snf4, demonstrating a direct interaction between the alpha- and gamma-subunits and indicating that our structure may represent the heterotrimer core of SNF1 in its activated state. Crystal structure of the heterotrimer core of Saccharomyces cerevisiae AMPK homologue SNF1.,Amodeo GA, Rudolph MJ, Tong L Nature. 2007 Sep 27;449(7161):492-5. Epub 2007 Sep 12. PMID:17851534 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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