2fh9
From Proteopedia
(New page: 200px<br /><applet load="2fh9" size="450" color="white" frame="true" align="right" spinBox="true" caption="2fh9, resolution 2.800Å" /> '''Structure and dimer...) |
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| - | [[Image:2fh9.gif|left|200px]]<br /><applet load="2fh9" size=" | + | [[Image:2fh9.gif|left|200px]]<br /><applet load="2fh9" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="2fh9, resolution 2.800Å" /> | caption="2fh9, resolution 2.800Å" /> | ||
'''Structure and dimerization of the kinase domain from yeast Snf1'''<br /> | '''Structure and dimerization of the kinase domain from yeast Snf1'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The Snf1/AMPK kinases are intracellular energy sensors, and the AMPK | + | The 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. |
==About this Structure== | ==About this Structure== | ||
| - | 2FH9 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http:// | + | 2FH9 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2FH9 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: kinase domain; dimer]] | [[Category: kinase domain; dimer]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:21:21 2008'' |
Revision as of 15:21, 21 February 2008
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Structure and dimerization of the kinase domain from yeast Snf1
Overview
The 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.
About this Structure
2FH9 is a Single protein structure of sequence from Saccharomyces cerevisiae. Full crystallographic information is available from OCA.
Reference
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
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