4RER: Crystal Structure Of The Phosphorylated Human Alpha1 Beta2 Gamma1 Holo-ampk Complex Bound To Amp And Cyclodextrin

Citation:
Abstract
AMP-activated protein kinase (AMPK) is a central cellular energy sensor and regulator of energy homeostasis, and a promising drug target for the treatment of diabetes, obesity, and cancer. Here we present low-resolution crystal structures of the human alpha1beta2gamma1 holo-AMPK complex bound to its allosteric modulators AMP and the glycogen-mimic cyclodextrin, both in the phosphorylated (4.05 A) and non-phosphorylated (4.60 A) state. In addition, we have solved a 2.95 A structure of the human kinase domain (KD) bound to the adjacent autoinhibitory domain (AID) and have performed extensive biochemical and mutational studies. Together, these studies illustrate an underlying mechanism of allosteric AMPK modulation by AMP and glycogen, whose binding changes the equilibria between alternate AID (AMP) and carbohydrate-binding module (glycogen) interactions.
PDB ID: 4RERDownload
MMDB ID: 125445
PDB Deposition Date: 2014/9/23
Updated in MMDB: 2014/12
Experimental Method:
x-ray diffraction
Resolution: 4.05  Å
Source Organism:
Similar Structures:
Biological Unit for 4RER: trimeric; determined by author and by software (PISA)
Molecular Components in 4RER
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-2(Gene symbol: PRKAB2)
Molecule annotation
1
5'-amp-activated Protein Kinase Subunit Gamma-1(Gene symbol: PRKAG1)
Molecule annotation
Chemicals (6 molecules)
1
1
2
1
3
1
4
3
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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