4RER

Crystal structure of the phosphorylated human alpha1 beta2 gamma1 holo-AMPK complex bound to AMP and cyclodextrin

Summary for 4RER

• Entry DOI: 10.2210/pdb4rer/pdb
• Related: 4RED 4REW
• Related PRD ID: PRD_900012
• Descriptor: 5'-AMP-activated protein kinase catalytic subunit alpha-1, 5'-AMP-activated protein kinase subunit beta-2, 5'-AMP-activated protein kinase subunit gamma-1, ... (7 entities in total)
• Functional Keywords: human alpha1 beta2 gamma1 holo-ampk complex, serine/threonine protein kinase, axin, camkkbeta, lkb1, glycogen, phosphorylation, transferase
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 3
• Total formula weight: 121560.24

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: 2014-09-23, release date: 2014-12-10, Last modification date: 2024-11-06)

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 (4.047 Å)