5UFU

Structure of AMPK bound to activator

Summary for 5UFU

• Entry DOI: 10.2210/pdb5ufu/pdb
• Descriptor: 5'-AMP-activated protein kinase catalytic subunit alpha-1, 5'-AMP-activated protein kinase subunit beta-1, 5'-AMP-activated protein kinase subunit gamma-1, ... (9 entities in total)
• Functional Keywords: kinase, ampk, activator, allostery, transferase-activator complex, transferase/activator
• Biological source: Rattus norvegicus (Rat); More
• Cellular location: Cytoplasm : Q5EG47
• Total number of polymer chains: 3
• Total formula weight: 120588.06

Authors

Calabrese, M.F.,Kurumbail, R.G. (deposition date: 2017-01-05, release date: 2017-05-17, Last modification date: 2024-11-20)

Primary citation

Cokorinos, E.C.,Delmore, J.,Reyes, A.R.,Albuquerque, B.,Kjbsted, R.,Jrgensen, N.O.,Tran, J.L.,Jatkar, A.,Cialdea, K.,Esquejo, R.M.,Meissen, J.,Calabrese, M.F.,Cordes, J.,Moccia, R.,Tess, D.,Salatto, C.T.,Coskran, T.M.,Opsahl, A.C.,Flynn, D.,Blatnik, M.,Li, W.,Kindt, E.,Foretz, M.,Viollet, B.,Ward, J.,Kurumbail, R.G.,Kalgutkar, A.S.,Wojtaszewski, J.F.P.,Cameron, K.O.,Miller, R.A.
Activation of Skeletal Muscle AMPK Promotes Glucose Disposal and Glucose Lowering in Non-human Primates and Mice.
Cell Metab., 25:1147-1159.e10, 2017

PubMed Abstract: The AMP-activated protein kinase (AMPK) is a potential therapeutic target for metabolic diseases based on its reported actions in the liver and skeletal muscle. We evaluated two distinct direct activators of AMPK: a non-selective activator of all AMPK complexes, PF-739, and an activator selective for AMPK β1-containing complexes, PF-249. In cells and animals, both compounds were effective at activating AMPK in hepatocytes, but only PF-739 was capable of activating AMPK in skeletal muscle. In diabetic mice, PF-739, but not PF-249, caused a rapid lowering of plasma glucose levels that was diminished in the absence of skeletal muscle, but not liver, AMPK heterotrimers and was the result of an increase in systemic glucose disposal with no impact on hepatic glucose production. Studies of PF-739 in cynomolgus monkeys confirmed translation of the glucose lowering and established activation of AMPK in skeletal muscle as a potential therapeutic approach to treat diabetic patients.

PubMed: 28467931
DOI: 10.1016/j.cmet.2017.04.010

Experimental method

X-RAY DIFFRACTION (3.45 Å)