2fh9
From Proteopedia
Structure and dimerization of the kinase domain from yeast Snf1
Structural highlights
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.[1] 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 PubMedThe Snf1/AMPK kinases are intracellular energy sensors, and the AMPK pathway has been implicated in a variety of metabolic human disorders. Here we report the crystal structure of the kinase domain from yeast Snf1, revealing a bilobe kinase fold with greatest homology to cyclin-dependant kinase-2. Unexpectedly, the crystal structure also reveals a novel homodimer that we show also forms in solution, as demonstrated by equilibrium sedimentation, and in yeast cells, as shown by coimmunoprecipitation of differentially tagged intact Snf1. A mapping of sequence conservation suggests that dimer formation is a conserved feature of the Snf1/AMPK kinases. The conformation of the conserved alphaC helix, and the burial of the activation segment and substrate binding site within the dimer, suggests that it represents an inactive form of the kinase. Taken together, these studies suggest another layer of kinase regulation within the Snf1/AMPK family, and an avenue for development of AMPK-specific activating compounds. Structure and dimerization of the kinase domain from yeast Snf1, a member of the Snf1/AMPK protein family.,Nayak V, Zhao K, Wyce A, Schwartz MF, Lo WS, Berger SL, Marmorstein R Structure. 2006 Mar;14(3):477-85. PMID:16531232[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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