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Science 315 (5819): 1726-1729

Copyright © 2007 by the American Association for the Advancement of Science

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

Robert Townley1, and Lawrence Shapiro1,2,3*

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

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

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

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