4RED

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

4RED の概要

• エントリーDOI: 10.2210/pdb4red/pdb
• 分子名称: 5'-AMP-activated protein kinase catalytic subunit alpha-1 (2 entities in total)
• 機能のキーワード: kinase domain fold, phosphorylate numerous cellular targets, upregulate atp-generating pathways upon activation, ampk beta and gamma subunits, transferase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm : Q13131
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 80400.47

構造登録者

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. (登録日: 2014-09-22, 公開日: 2014-12-10, 最終更新日: 2023-09-20)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.95 Å)