4ZHX

Novel binding site for allosteric activation of AMPK

4ZHX の概要

• エントリーDOI: 10.2210/pdb4zhx/pdb
• 分子名称: 5'-AMP-activated protein kinase catalytic subunit alpha-2, 5'-AMP-activated protein kinase subunit beta-1, 5'-AMP-activated protein kinase subunit gamma-1, ... (8 entities in total)
• 機能のキーワード: transferase, serine/threonine kinase, allosteric activation, nucleotide-binding
• 由来する生物種: Homo sapiens (Human); 詳細
• 細胞内の位置: Cytoplasm : P54646
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 268115.07

構造登録者

Langendorf, C.G.,Ngoei, K.R.,Issa, S.M.A.,Ling, N.,Gorman, M.A.,Parker, M.W.,Sakamoto, K.,Scott, J.W.,Oakhill, J.S.,Kemp, B.E. (登録日: 2015-04-27, 公開日: 2016-03-09, 最終更新日: 2024-11-20)

主引用文献

Langendorf, C.G.,Ngoei, K.R.,Scott, J.W.,Ling, N.X.,Issa, S.M.,Gorman, M.A.,Parker, M.W.,Sakamoto, K.,Oakhill, J.S.,Kemp, B.E.
Structural basis of allosteric and synergistic activation of AMPK by furan-2-phosphonic derivative C2 binding.
Nat Commun, 7:10912-10912, 2016

PubMed Abstract: The metabolic stress-sensing enzyme AMP-activated protein kinase (AMPK) is responsible for regulating metabolism in response to energy supply and demand. Drugs that activate AMPK may be useful in the treatment of metabolic diseases including type 2 diabetes. We have determined the crystal structure of AMPK in complex with its activator 5-(5-hydroxyl-isoxazol-3-yl)-furan-2-phosphonic acid (C2), revealing two C2-binding sites in the γ-subunit distinct from nucleotide sites. C2 acts synergistically with the drug A769662 to activate AMPK α1-containing complexes independent of upstream kinases. Our results show that dual drug therapies could be effective AMPK-targeting strategies to treat metabolic diseases.

PubMed: 26952388
DOI: 10.1038/ncomms10912

実験手法

X-RAY DIFFRACTION (2.99 Å)