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Published Online February 8, 2007
Science DOI: 10.1126/science.1137503

Reports

Submitted on November 13, 2006
Accepted on February 1, 2007

Crystal Structures of the Adenylate Sensor from Fission Yeast AMP-Activated Protein Kinase

Robert Townley 1 and Lawrence Shapiro 2*

1 Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032 USA.
2 Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032 USA;Edward S. Harkness Eye Institute, Columbia University, New York, NY 10032 USA; Naomi Berrie Diabetes Center, Columbia University, New York, NY 10032 USA.

* To whom correspondence should be addressed.
Lawrence Shapiro , E-mail: LSS8{at}columbia.edu

The 5'-AMP (adenosine monophosphate)-activated protein kinase (AMPK) coordinates metabolic function with energy availability by responding to changes in intracellular adenosine triphosphate (ATP) and AMP levels. Here we report crystal structures at 2.6 and 2.9 Å resolution for ATP- and AMP-bound forms of a core {alpha}{beta}{gamma} adenylate-binding domain from the fission yeast AMPK homologue. ATP and AMP bind competitively to a single site in the {gamma} subunit, with their respective phosphate groups positioned near function-impairing mutants. Surprisingly, ATP binds without counter ions, amplifying its electrostatic effects on a critical regulatory region where all three subunits converge.


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