4RED

Crystal structure of human AMPK alpha1 KD-AID with K43A mutation

Summary for 4RED

• Entry DOI: 10.2210/pdb4red/pdb
• Descriptor: 5'-AMP-activated protein kinase catalytic subunit alpha-1 (2 entities in total)
• Functional Keywords: kinase domain fold, phosphorylate numerous cellular targets, upregulate atp-generating pathways upon activation, ampk beta and gamma subunits, transferase
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm : Q13131
• Total number of polymer chains: 2
• Total formula weight: 80400.47

Authors

Zhou, X.E.,Ke, J.,Li, X.,Wang, L.,Gu, X.,de Waal, P.W.,Tan, M.H.E.,Wang, D.,Wu, D.,Xu, H.E.,Melcher, K. (deposition date: 2014-09-22, release date: 2014-12-10, Last modification date: 2023-09-20)

Primary citation

Li, X.,Wang, L.,Zhou, X.E.,Ke, J.,de Waal, P.W.,Gu, X.,Tan, M.H.,Wang, D.,Wu, D.,Xu, H.E.,Melcher, K.
Structural basis of AMPK regulation by adenine nucleotides and glycogen.
Cell Res., 25:50-66, 2015

PubMed 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 α1β2γ1 holo-AMPK complex bound to its allosteric modulators AMP and the glycogen-mimic cyclodextrin, both in the phosphorylated (4.05 Å) and non-phosphorylated (4.60 Å) state. In addition, we have solved a 2.95 Å 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.

PubMed: 25412657
DOI: 10.1038/cr.2014.150

Experimental method

X-RAY DIFFRACTION (2.95 Å)