4QFS: Structure of AMPK in complex with Br2-A769662core activator and STAUROSPORINE inhibitor

Citation:
Abstract
AMP-activated protein kinase (AMPK) is a principal metabolic regulator affecting growth and response to cellular stress. Comprised of catalytic and regulatory subunits, each present in multiple forms, AMPK is best described as a family of related enzymes. In recent years, AMPK has emerged as a desirable target for modulation of numerous diseases, yet clinical therapies remain elusive. Challenges result, in part, from an incomplete understanding of the structure and function of full-length heterotrimeric complexes. In this work, we provide the full-length structure of the widely expressed alpha1beta1gamma1 isoform of mammalian AMPK, along with detailed kinetic and biophysical characterization. We characterize binding of the broadly studied synthetic activator A769662 and its analogs. Our studies follow on the heels of the recent disclosure of the alpha2beta1gamma1 structure and provide insight into the distinct molecular mechanisms of AMPK regulation by AMP and A769662.
PDB ID: 4QFSDownload
MMDB ID: 156757
PDB Deposition Date: 2014/5/21
Updated in MMDB: 2017/12
Experimental Method:
x-ray diffraction
Resolution: 3.55  Å
Source Organism:
Similar Structures:
Biological Unit for 4QFS: trimeric; determined by author and by software (PISA)
Molecular Components in 4QFS
Label Count Molecule
Proteins (3 molecules)
1
5'-amp-activated Protein Kinase Catalytic Subunit Alpha-1(Gene symbol: Prkaa1)
Molecule annotation
1
5'-amp-activated Protein Kinase Subunit Beta-1(Gene symbol: Prkab1)
Molecule annotation
1
5'-amp-activated Protein Kinase Subunit Gamma-1(Gene symbol: Prkag1)
Molecule annotation
Chemicals (10 molecules)
1
1
2
1
3
5
4
1
5
2
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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